RESUMO
Posttransplant cyclophosphamide (PtCy) has been shown to decrease post-hematopoietic stem cell transplant acute and chronic graft-versus-host disease (GVHD). In this study, PtCy was used in 44 patients along with mycophenolate and tacrolimus with HLA matched (29) and mismatched (15) unrelated donors to determine the impact of graft content on outcome; thus, all patients had flow cytometric analysis of their graft content including the number of B cells, NK cells, and various T cell subsets. Higher γδ T cell dose was associated with the development of acute GVHD (p = .0038). For PtCy, further studies of the cell product along with further graft manipulation, such as selective γδ T cell depletion, could potentially improve outcomes.
Assuntos
Ciclofosfamida , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco de Sangue Periférico , Doadores não Relacionados , Humanos , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Estudos Prospectivos , Imunossupressores/uso terapêutico , Linfócitos T/imunologia , Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Idoso , Adulto Jovem , Resultado do Tratamento , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Adolescente , Condicionamento Pré-Transplante/métodosRESUMO
Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) has been introduced for the mobilization of peripheral blood stem cells (PBSCs). However, no cases of acute lung injury (ALI) in healthy donors have been reported, and the underlying mechanisms remain poorly understood. We first reported a case of ALI caused by PEG-rhG-CSF in a healthy Chinese donor, characterized by hemoptysis, hypoxemia, and patchy shadows. Ultimately, hormone administration, planned PBSC collection, leukocyte debridement, and planned PBSC collection resulted in active control of the donor's ALI. The donor's symptoms improved without any adverse effects, and the PBSC collection proceeded without incident. Over time, the lung lesion was gradually absorbed and eventually returned to normal. PEG-rhG-CSF may contribute to ALI in healthy donors via mechanisms involving neutrophil aggregation, adhesion, and the release of inflammatory mediators in the lung. This case report examines the clinical manifestations, treatment, and mechanism of lung injury induced by PEG-rhG-CSF-mobilized PBSCs.
Assuntos
Lesão Pulmonar Aguda , Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas , Polietilenoglicóis , Proteínas Recombinantes , Humanos , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/métodos , Polietilenoglicóis/efeitos adversos , Masculino , Adulto , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Células-Tronco de Sangue Periférico , Doadores de Tecidos , Doadores de SangueRESUMO
BACKGROUND: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. METHODS: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. RESULTS: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. CONCLUSIONS: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.
Assuntos
Composição Corporal , Linfoma , Transplante de Células-Tronco de Sangue Periférico , Transplante Autólogo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Linfoma/terapia , Linfoma/mortalidade , Doença Crônica , Idoso , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Adulto , Músculo EsqueléticoRESUMO
ABSTRACT: Allogeneic hematopoietic cell transplantation is a life-saving procedure used to treat a variety of devastating diseases. It requires hematopoietic stem cells collected via filgrastim-mobilized peripheral blood stem cells (PBSCs) or bone marrow (BM) harvest from volunteer unrelated donors (URDs). There is a paucity of safety data regarding donors' long-term adverse events. This prospective, observational study combined PBSC donors enrolled in the NMDP Investigational New Drug trial and BM donors between 1 July 1999 and 30 September 2015. The primary objective was to describe the long-term incidence of myeloid malignancies. The secondary objectives included describing the long-term incidence of lymphoid malignancies, nonhematologic malignancies, autoimmune disorders, and thrombotic events. A total of 21 643 donors (14 530 PBSCs and 7123 BM) were included. The incidence rate of myeloid disorders per 100 000 person-years in donors of PBSCs was 2.53 (95% confidence interval [CI], 0.82-7.84) and in donors of BM, it was 4.13 (95% CI, 1.33-12.8). The incidence rate ratio of PBSCs/BM donors was 0.61 (95% CI, 0.12-3.03; P = .55). The incidence of other malignancies, autoimmunity, and thrombosis did not differ between the donor types. This comprehensive study of the long-term effects of filgrastim in URDs of PBSCs provides strong evidence that donors who receive filgrastim are not at an increased risk of these events compared with BM donors. It also provides reassurance to current donors undergoing stem cell mobilization as well as individuals considering joining stem cell registries, such as NMDP.
Assuntos
Filgrastim , Mobilização de Células-Tronco Hematopoéticas , Humanos , Filgrastim/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Células-Tronco de Sangue Periférico , Doadores não Relacionados , Estudos Prospectivos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adulto Jovem , Incidência , Adolescente , Resultado do TratamentoRESUMO
PURPOSE: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and subsequent post-aPBSCT risk of t-MN in patients with non-HL, information about patients with HL treated with aPBSCT is not available. METHODS: We constructed a retrospective cohort of 321 patients with HL transplanted at a median age of 34 years (range, 18-71). Targeted DNA sequencing of PBSC products performed for CH-associated or myeloid malignancy-associated genes identified pathogenic mutations in these patients. RESULTS: CH was identified in the PBSC product of 46 patients (14.3%) with most prominent representation of DNMT3A (n = 25), PPM1D (n = 7), TET2 (n = 7), and TP53 (n = 5) mutations. Presence of CH in the PBSC product was an independent predictor of t-MN (adjusted hazard ratio [aHR], 4.50 [95% CI, 1.54 to 13.19]). Notably all patients with TP53 mutations in the PBSC product developed t-MN, whereas none of the patients with DNMT3A mutations alone (without co-occurring TP53 or PPM1D mutations) did. Presence of TP53 and/or PPM1D mutations was associated with a 7.29-fold higher hazard of t-MN when compared with individuals carrying no CH mutations (95% CI, 1.72 to 30.94). The presence of TP53 and/or PPM1D mutations was also associated with a 4.17-fold higher hazard of nonrelapse mortality (95% CI, 1.25 to 13.87). There was no association between CH and relapse-related mortality. CONCLUSION: The presence of TP53 and/or PPM1D mutations in the PBSC product increases the risk of post-aPBSCT t-MN and nonrelapse mortality among patients with HL and may support alternative therapeutic strategies.
Assuntos
Hematopoiese Clonal , Doença de Hodgkin , Mutação , Segunda Neoplasia Primária , Transplante Autólogo , Humanos , Doença de Hodgkin/terapia , Doença de Hodgkin/genética , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adolescente , Transplante Autólogo/efeitos adversos , Hematopoiese Clonal/genética , Adulto Jovem , Idoso , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/etiologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Proteína Supressora de Tumor p53/genética , DNA Metiltransferase 3A , Proteína Fosfatase 2C/genética , DNA (Citosina-5-)-Metiltransferases/genética , Dioxigenases , Proteínas de Ligação a DNA/genética , Proteínas Proto-Oncogênicas/genéticaRESUMO
Objectives: To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases. Methods: A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021. Results: â The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9-22) days and 13 (10-24) days, respectively (P=0.834), whereas the median implantation time for platelets was 15 (7-103) days and 14 (8-38) days, respectively (P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% (P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% (P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. â¡The cumulative incidence rates of grade â ¡-â £ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% -38.1% ) and 28.8% (95% CI 17.2% -41.6% (P=0.965), respectively. The cumulative incidence rates of grade â ¢/â £ acute GVHD were 7.8% (95% CI 3.6% -14.0% ) and 9.6% (95% CI 3.5% -19.5% ) (P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% -44.1% ), respectively (P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively (P=0.840). â¢The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% -20.5% ) and 10.0% (95% CI 3.6% -20.2% ), respectively (P=0.341), and the NRM were 14.7% (95% CI 8.4% -22.6% ) and 16.2% (95% CI 7.4% -28.0% ), respectively (P=0.681). â£The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% -90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively (P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% -79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively (P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% -79.3% ), respectively (P=0.284) . Conclusion: The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Doadores não Relacionados , Sangue Fetal , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/complicações , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversosRESUMO
BACKGROUND: Haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PTCy) is an important therapeutic option for patients lacking an HLA-matched donor. However, the significance of CD34+ cell dose in grafts has not been fully elucidated. OBJECTIVE: We aimed to explore the impact of CD34+ cell dose on outcomes after haplo-PBSCT with PTCy. STUDY DESIGN: We retrospectively investigated 111 consecutive patients who underwent haplo-PBSCT with PTCy or HLA-matched PBSCT from related donors. RESULTS: There were no statistically significant differences in 3-year overall survival (p = 0.559) or progression-free survival (p = 0.974) between haplo-PBSCT and matched PBSCT. Delayed neutrophil engraftment and a lower incidence of graft-versus-host disease were observed in haplo-PBSCT. The median dose of CD34+ cells was 4.9 × 106 /kg in 57 haplo-PBSCT and 4.5 × 106 /kg in 54 matched PBSCTs. Importantly, patients who underwent haplo-PBSCT with the administration of CD34+ cell at a dose of ≥4.0 × 106 /kg significantly had improved OS (p = 0.015) and decreased incidence of disease relapse (p = 0.001) without increasing incidence of GVHD. CONCLUSION: Our data suggest that a higher dose of CD34+ cells in haplo-PBSCT with PTCy positively impacts the outcomes without an increase of GVHD.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Japão , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Condicionamento Pré-Transplante/efeitos adversosRESUMO
AIM: Chronic graft versus host disease (cGVHD) is a major cause of morbidity postallogeneic peripheral blood stem cell transplant (PBSCT). There is paucity of literature describing incidence, risk factors, characteristics, and outcome of cGVHD in children undergoing haploidentical PBSCT with post-transplant cyclophosphamide (PTCy). Here, we describe our experience from our center regarding the same. METHODS: All children who underwent haploidentical PBSCT with PTCy between January 2016 and December 2021 at our center and survived beyond day+100 post-transplant were included in this retrospective study. Conditioning regimens used were: Thiotepa-Fludarabine-Cyclophosphamide with 2 Gy single fraction total body irradiation, Thiotepa-Busulfan-Fludarabine, Fludarabine-total body irradiation and Fludarabine-Melphalan. Peripheral blood was used as stem cell source in all patients. GVHD prophylaxis was PTCy 50 mg/kg on day +3 and +4, Mycophenolate mofetil and Calcineurin inhibitors. Clinical and laboratory data was electronically retrieved and analyzed based on National Institute of Health Consensus Criteria-2014 at regular intervals. Impact of various patient, donor, and transplant-related factors on development of cGVHD were analyzed. Incidence of relapse, event free survival (EFS) and overall survival (OS) were calculated and compared between cGVHD and no cGVHD groups. Patients with rejection were excluded from risk factor analysis for cGVHD but were considered for survival analysis. RESULTS: Fifty-one children included in this study. Median age of transplant of our cohort was 7.5 years with male:female=1.6:1. Eight patients had rejection with autologous recovery. History of acute GVHD (aGVHD) was present in 15/51 (Grade III to IV in 7/51). cGVHD developed in 19/51 patients (mild-9/51, moderate-6/51, and severe-4/51). Skin was the most common organ involved (100%) followed by gastrointestinal tract (47.4%), liver (36.8%), eyes (21%), lungs (21%), mouth (15.7%), and joints (5.2%). Advanced donor age (>30 y) and previous aGVHD were found to be significantly associated with increased risk of developing cGVHD. At last follow-up, complete response and partial response of cGVHD was seen in 6/19 and 4/19 patients, respectively. Overall mortality was 15/51 (cause of mortality was relapse of cancer 8/15, cGVHD-3/15, other 4/15). EFS and OS of full cohort was 55% and 70.6%, respectively. Compared with patients without cGVHD, patients with cGVHD demonstrated a lower relapse (18.2% vs. 40%, P =0.2333), higher EFS (68.4% vs. 53.1%, P =0.283), and higher OS (73.7% vs. 68.8%, P =0.708). CONCLUSION: Incidence of cGVHD was high in children undergoing haploidentical PBSCT with PTCy. Other than PBSC graft source; donor age and previous aGVHD were the risks factors for development of cGVHD. Patients with cGVHD had lower incidence of relapse translating into better survival but this difference was not statistically significant.
Assuntos
Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Criança , Humanos , Masculino , Feminino , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Incidência , Tiotepa/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Fatores de Risco , Recidiva , Condicionamento Pré-Transplante/efeitos adversosRESUMO
Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor HCT. A phase II study from the Moffitt Cancer Center substituting sirolimus (Siro) for Tac in this prophylactic regimen reported comparable rates of grade II-IV acute GVHD (aGVHD). Many centers have substituted Siro for Tac in this setting based on a preferable side effect profile, although comparative data are limited. In this study, we retrospectively compared outcomes in haplo-HCT with PTCy/Siro/MMF versus haplo-HCT with PTCy/Tac/MMF. The study cohort included all consecutive patients receiving haploidentical donor T cell-replete peripheral blood stem cell (PBSC) HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. A total of 423 patients were included, of whom 84 (20%) received PTCy/Siro/MMF and 339 (80%) received PTCy/Tac/MMF. The median age for the entire cohort was 54 years (range, 18 to 78 years), and the median follow-up was 30 months. The Siro group had a higher proportion of patients age ≥60 years (58% versus 34%; P < .01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV aGVHD (45% versus 47%; P = .6) at day +100 or chronic GVHD (cGVHD) (47% versus 54%; P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better in the Tac group (odds ratio, .30; 95% confidence interval, .1 to .83; P = .02), with a median time to engraftment of 17 days versus 18 days in the Siro group, but platelet engraftment was similar in the 2 groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on aGVHD or cGVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease-free survival, or overall survival after PBSC haplo-HCT. These findings suggest that Siro is a comparable alternative to Tac in combination with PTCy/MMF for GVHD prophylaxis, with overall similar clinical outcomes despite delayed engraftment after peripheral blood stem cell haplo-HCT. Although Tac remains the standard of care, Siro may be substituted based on the side effect profile of these medications, with consideration of patient medical comorbidities at HCT.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco de Sangue Periférico , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Tacrolimo/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/métodos , Sirolimo/uso terapêutico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Ácido Micofenólico/uso terapêuticoRESUMO
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most important curative method for intermediate- and high-risk adult acute myeloid leukemia (AML) patients. We aimed to identify the clinical outcomes of haploidentical related donor (HID) peripheral blood stem cell transplantation (PBSCT) who receiving peripheral blood (G-PB) harvest, and the patients receiving bone marrow (BM) plus G-PB harvest (BM + PB) as grafts were enrolled as control. The engraftments of neutrophil and platelet in G-PB group were both faster than those in BM + PB group. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGVHD), and moderate to severe chronic GVHD (cGVHD) were all comparable between G-PB and BM + PB groups. The cumulative incidence of relapse and non-relapse mortality at 3 years after HID HSCT was 12.6% versus 13.7% (p = 0.899) and 3.6% versus 7.3% (p = 0.295), respectively, in G-PB and BM + PB group. While the probabilities of GVHD-free/relapse-free survival, leukemia-free survival, and overall survival at 3 years after HID HSCT were 60.6% versus 53.4% (p = 0.333), 83.8% versus 79.0% (p = 0.603), and were 87.3% versus 82.9% (p = 0.670), respectively. We confirmed the safety and efficacy of HID PBSCT in intermediate- and high-risk AML patients in a large cohort.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transplante de Células-Tronco de Sangue Periférico , Humanos , Adulto , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Recidiva , Leucemia Mieloide Aguda/complicações , Estudos RetrospectivosRESUMO
There is a limited body of evidence for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in older patients. Previous studies have used a high proportion of bone marrow-derived grafts and a variety of conditioning regimens. In Australia and New Zealand, haplo-HCST is predominantly performed using peripheral blood (PB) with universal use of post-transplantation cyclophosphamide (PTCy). To characterize the outcomes of older recipients undergoing haplo-HSCT for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Data were collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB haplo-HSCT for AML/MDS between January 2010 and July 2020. A total of 44 patients were included in the analysis. The median follow-up time was 377 days. The median age was 68 (range 65-74) with a median Karnofsky performance status of 90. Thirty patients (68.2%) had AML, whereas 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was nonmyeloablative fludarabine, cyclophosphamide, and total body irradiation (75%); the remainder of the patients received either melphalan- or busulfan-based regimens, and the majority were reduced intensity, with only 2 patients undergoing myeloablative conditioning. All patients received post-transplantation cyclophosphamide and mycophenolate mofetil, with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporine (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients at a median of 18 days, whereas platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of cytomegalovirus (CMV) reactivation and CMV disease were 52.5% and 5.1% at 1 year. The incidence of grade 2-4 acute Graft Versus Host Disease (GVHD) was 18.2%. The incidence of chronic GVHD at 2 years was 40.7%, with extensive chronic GVHD occurring in 17.7% of patients. The incidences of relapse and non-relapse mortality (NRM) at 2 years were 8.8% and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year overall survival was 74%. Relapse free survival and GVHD free, relapse free survival at 2 years was 70% and 48%. Haplo-HSCT using a peripheral blood graft and PTCy GVHD prophylaxis demonstrates long-term disease control with acceptable rates of NRM for older patients with AML/MDS.
Assuntos
Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Idoso , Nova Zelândia/epidemiologia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Síndromes Mielodisplásicas/terapia , RecidivaRESUMO
Allogeneic hematopoietic cell transplantation (allo-HCT) is the sole curative therapy for myelodysplastic syndrome (MDS). In the absence of an HLA-matched sibling donor, an HLA-matched unrelated donor (MUD) is considered the leading candidate. However, in recent decades, the alternative donor pool has been extended to HLA-haploidentical donors, especially with the development of graft-versus-host disease (GVHD) prophylaxis using post-transplantation cyclophosphamide (PTCy). Comparative data for haploidentical and MUD allo-HCT in patients with MDS are scarce. We retrospectively analyzed 697 adult patients with MDS who underwent HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with PTCy (n = 136), MUD bone marrow transplantation (MUD-BMT) (n = 465), or MUD peripheral blood stem cell transplantation (MUD-PBSCT) (n = 96) as their first allo-HCT between 2014 and 2020 using Japanese registry data. Multivariable analyses demonstrated faster neutrophil engraftment (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.65 to 2.90; P < .001) and platelet engraftment (HR, 2.31; 95% CI, 1.72 to 3.10; P < 0001) in the MUD-PBSCT cohort compared with the haplo-PBSCT cohort. MUD-BMT was associated with a higher incidence of grade II-IV acute GVHD than haplo-PBSCT (HR, 1.52; 95% CI, 1.00 to 2.29; P = .048). Among patients without in vivo T cell depletion using antithymocyte globulin (ATG) (haplo-PBSCT, n = 136; MUD-BMT, n = 446; MUD-PBSCT, n = 65), MUD-PBSCT recipients experienced faster hematopoietic recovery, MUD-BMT recipients (HR, 1.54; 95% CI, 1.02 to 2.32; P = .042) or MUD-PBSCT recipients (HR, 1.83; 95% CI, 1.06 to 3.18; P = .03) had a higher incidence of grade II-IV acute GVHD, and MUD-PBSCT recipients developed chronic GVHD more frequently than haplo-PBSCT recipients (HR, 1.74; 95% CI, 1.04 to 2.89; P = .034). There were no significant differences in overall survival, disease-free survival, GVHD-free relapse-free survival, relapse, or nonrelapse mortality in the haplo-PBSCT cohort versus the MUD-BMT or MUD-PBSCT cohorts. In conclusion, despite differences in the incidences of hematopoietic engraftment and GVHD depending on graft type and ATG use in MUD transplant recipients, major transplantation outcomes were comparable between recipients of haplo-PBSCT using PTCy and recipients of MUD-BMT or MUD-PBSCT.
Assuntos
Doença Enxerto-Hospedeiro , Síndromes Mielodisplásicas , Transplante de Células-Tronco de Sangue Periférico , Adulto , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Doadores não Relacionados , Estudos Retrospectivos , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Síndromes Mielodisplásicas/terapiaRESUMO
Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.
Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Humanos , Soro Antilinfocitário/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Seguimentos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Infecções por Vírus Epstein-Barr/complicações , Células-Tronco de Sangue Periférico/patologia , Herpesvirus Humano 4 , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/patologia , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: To investigate the impact of natural killer (NK) cells in the graft on the outcome following haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). METHODS: We retrospectively collected data from patients who had undergone haplo-PBSCT at our centre from January 2019 to November 2021. The percentage of NK cells in stem cell grafts was detected by flow cytometry. Based on the median (range) count of NK cells (1.8 [0.4-6.0] × 108/kg), patients were separated into high and low NK cell count groups. RESULTS: Data from 96 patients were analysed. Patients were evenly distributed (48 in each group) into high and low NK cell count groups. There was no significant difference in neutrophil and platelet recovery between the two groups. However, the rates of febrile neutropenia, bacterial infection, and invasive fungal disease (IFD) were significantly reduced in the high compared with the low NK cell count group. There was no significant difference in rates of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections between groups. There was no significant difference between groups in grades II and above acute graft versus host disease (GVHD), progression-free survival (PFS), or overall survival (OS). CONCLUSION: A high number of NK cells in the graft may reduce febrile neutropenia, IFD and bacterial infection following haplo-PBSCT but it has no significant effect on aGVHD, PFS, or OS.
Assuntos
Infecções por Vírus Epstein-Barr , Neutropenia Febril , Transplante de Células-Tronco de Sangue Periférico , Humanos , Herpesvirus Humano 4 , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Estudos Retrospectivos , Células Matadoras NaturaisRESUMO
Umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) are effective allogeneic treatments for patients with malignant and non-malignant refractory hematological diseases. However, the differences in the immune cell reconstitution and the immune reactions during initial stages post-transplantation are not well established between UCBT and PBSCT. Therefore, in this study, we analyzed the differences in the immune reactions during the early stages (days 7-100 post-transplantation) such as pre-engraftment syndrome (PES), engraftment syndrome (ES), and acute graft-versus-host disease (aGVHD) and the immune cell reconstitution between the UCBT and the PBSCT group of patients. We enrolled a cohort of patients that underwent UCBT or PBSCT and healthy controls (n=25 each) and evaluated their peripheral blood mononuclear cell (PBMC) samples and plasma cytokine (IL-10 and GM-CSF) levels using flow cytometry and ELISA, respectively. Our results showed that the incidences of early immune reactions such as PES, ES, and aGVHD were significantly higher in the UCBT group compared to the PBSCT group. Furthermore, in comparison with the PBSCT group, the UCBT group showed higher proportion and numbers of naïve CD4+ T cells, lower proportion and numbers of Tregs, higher proportion of CD8+ T cells with increased activity, and higher proportion of mature CD56dim CD16+ NK cells during the early stages post-transplantation. Moreover, the plasma levels of GM-CSF were significantly higher in the UCBT group compared to the PBSCT group in the third week after transplantation. Overall, our findings demonstrated significant differences in the post-transplantation immune cell reconstitution between the UCBT and the PBSCT group of patients. These characteristics were associated with significant differences between the UCBT and the PBSCT groups regarding the incidences of immune reactions during the early stages post transplantation.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Leucócitos Mononucleares , Linfócitos T CD8-Positivos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologiaRESUMO
The contribution of lymphocyte subset composition of the graft on the outcomes following haploidentical peripheral blood stem cell transplantation (haploPBSCT) is not fully elucidated. We retrospectively analyzed 314 patients with hematological malignancies who underwent haploPBSCT from 2016 to 2020 in our center. We obtained a cutoff value of CD3+ T cell dose (2.96 × 108/kg) that separated the risk of II-IV acute graft-versus-host disease (aGvHD) and divided patients into the low CD3+ T cell dose group (CD3+ low) and the high CD3+ T cell dose (CD3+ high) group. Significantly higher incidences of I-IV aGvHD, II-IV aGvHD, and III-IV aGvHD were identified in the CD3+ high group (50.8%, 19.8%, and 8.1% in the high group, 23.1%, 6.0%, and 0.9% in the low group, P < 0.0001, P = 0.002, and P = 0.02, respectively). We found that CD4+ T cell and its naïve and memory subpopulations of grafts had a significant impact on aGvHD (P = 0.005, P = 0.018, and P = 0.044). Besides, we found an inferior reconstitution of natural killer (NK) cells in the CD3+ high group than in the low group within the first-year posttransplant (239 cells/µL vs 338 cells/µL, P = 0.0003). No differences in engraftment, chronic GvHD (cGvHD), relapse rate, transplant-related mortality (TRM), and overall survival (OS) were identified between the two groups. In conclusion, our study found that a high CD3+ T cell dose led to a high risk of aGvHD and inferior reconstitution of NK cells in the haploPBSCT setting. In the future, carefully manipulating the composition of lymphocyte subsets of grafts might reduce the risk of aGvHD and improve the transplant outcome.
Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia , Doença Enxerto-Hospedeiro/etiologia , Subpopulações de Linfócitos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-TransplanteRESUMO
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer under the age of 15 years. Despite the recent advances in therapeutic regimens, relapse occurs in 15%-20% of pediatric patients after chemotherapy, and hematopoietic stem cell transplantation (HSCT) is the best treatment option. However, donor availability is one of the major challenges. Over the last decade, haploidentical donor (HID) transplantation has evolved as an alternative option. Herein, we aimed to compare the transplant outcomes in pediatric patients receiving total body irradiation (TBI)-free myeloablative regimens, between non-HID and HID transplant. PATIENTS AND METHODS: The study included 60 pediatric ALL patients who had undergone HSCT from October 2016 until September 2020. Forty-three patients received non-HID HSCT, while 17 patients received HID. The sources of stem cells (SC) were peripheral blood stem cells (PBSC) for all the patients. The conditioning regimen was based on busulfan and cyclophosphamide. For graft-versus-host disease (GvHD) prophylaxis, patients received cyclosporine and methotrexate in the setting of non-HID transplantation, where HIDs received post-transplant cyclosporine and cyclophosphamide. RESULTS: The cumulative incidences of 3-year overall survival (OS) were 73.1%, 66.6%, and 69.5%, for matched sibling donor-matched related donor (MSD-MRD), matched unrelated donor-mismatched unrelated donor (MUD-MMUD), and HID groups, respectively (p = .85). The cumulative incidences of grade II-IV acute GvHD for the MRD, MUD-MMUD, and HID groups were 29%, 41%, and 49%, respectively (p = .47). Furthermore, the 3-year cumulative incidence of chronic GvHD was MSD-MRD: 70% versus MUD-MMUD: 42% versus HID: 45% (p = .64). The 3-year cumulative incidence of relapse post transplantation was 45%, 18%, and 45%, respectively, for the MSD-MRD, MUD-MMUD, and HID groups, and the differences were not statistically significant (p = .55). There was a higher risk for cytomegalovirus (CMV) infection in patients receiving HID transplants compared to those of non-HIDs (p < .01). CONCLUSION: Our results indicate that PBSC-HID transplant outcomes in the setting of non-TBI conditioning are comparable to those of non-HIDs in pediatric ALL patients.
Assuntos
Ciclosporinas , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Adolescente , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Doadores não Relacionados , Transplante Homólogo/efeitos adversos , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Recidiva , Condicionamento Pré-Transplante/métodos , Estudos RetrospectivosRESUMO
Graft-versus-host disease (GVHD) is a major complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Previous randomized studies have already shown that the use of several types of antihuman T lymphocyte immune globulin (ATG) as GVHD prophylaxis can reduce the incidence of acute GVHD and chronic GVHD. However, the efficacy and safety of PBSCT from HLA-identical donors with low-dose ATG remain unclear. This study aimed to clarify the efficacy and safety of PBSCT from HLA-identical donors with low-dose ATG compared with PBSCT from HLA-identical donors without ATG. To do so, we retrospectively analyzed the outcomes of patients who underwent allogeneic PBSCT from HLA-identical donors with low-dose ATG-thymoglobulin (ATG-T; 2.5 mg/kg) versus those who did not receive ATG-T. Patient data were collected retrospectively from the medical records of Anjo Kosei Hospital. This study was conducted from 2009 to the final follow-up in October 2022. Forty-seven of 91 patients received ATG-T between January 2009 and March 2020. ATG-T reduced the incidence rates of moderate-to-severe chronic GVHD (hazard ratio [HR], .15; 95% confidence interval [CI], .057 to .41; P < .0010) and nonrelapse mortality (HR, .21; 95% CI, .0058 to.75, P = .016) without increasing the risk of relapse. Overall survival did not differ significantly between the 2 groups; however, the low-dose ATG-T group had better moderate-to-severe chronic GVHD-free, relapse-free survival rates (HR, .47; 95% CI, .27 to .80, P = .0054) than the non-ATG-T group. In addition, multistate analysis revealed that the low-dose ATG-T group had better current GVHD-free, relapse-free survival at 24 months after transplantation (45% [95% CI, 29% to 63%)] versus 21% [95% CI, 9.1% to 34%]; P = .015). Low-dose ATG-T was not associated with increased incidence of infections or adverse events. Our findings suggest that low-dose ATG-T can be beneficial for patients receiving PBSCT from HLA-identical donors. © 2023 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Soro Antilinfocitário/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/prevenção & controle , RecidivaRESUMO
Post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is being increasingly used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donors (MRDs); however, information regarding the transfusion needs in this setting is lacking. This study compared RBC and platelet units transfused and time to transfusion independence according to the GVHD prophylaxis regimen in MRD HSCT. We performed a matched-pair analysis comparing the transfusion requirements and the clinical outcomes of patients who underwent MRD peripheral blood HSCT using PTCy between January 2017 and June 2021 (n = 100) with historical MRD HSCTs using standard cyclosporine A (CsA)-based prophylaxis (n = 100). Neutrophil engraftment was significantly delayed in the PTCy group compared with the CsA group (16 days versus 13 days; P = .003). PTCy was associated with increased RBC (median, 5 units versus 4 units; P = .04) and platelet (median, 6 units versus 3 units; P = .01) transfusion requirements during the first 30 days after transplantation. The proportion of patients requiring platelet transfusion during days 31 to 90 after transplantation was also higher in the PTCy group (55% versus 25%; P < .0001). In multivariate analysis, PTCy was associated with delayed RBC and platelet transfusion independence (hazard ratio, .61 [P = .007] and .51 [P < .0001], respectively). The cumulative incidence (CuI) of BK polyomavirus-associated hemorrhagic cystitis grade ≥2 at 100 days was higher in the PTCy group (34% versus 12%; P < .0001); however, the PTCy group had lower rates of grade II-IV acute GVHD (100-day CuI, 57% versus 23%; P < .0001) and moderate to severe chronic GVHD (1-year CuI, 49% versus 28%; P = .003), as well as better 2-year overall survival (74% versus 56%; P = .01). Our study shows that although PTCy increases the transfusion burden in MRD HSCT, it is associated with a low incidence of severe GVHD and with encouraging survival outcomes.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Irmãos , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , CiclosporinaRESUMO
The kinetics of early and late cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are poorly defined. We retrospectively compared CMV reactivation and disease among 780 seropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and calcineurin inhibitor plus posttransplantation cyclophosphamide (PTCy; n = 44), mycophenolate mofetil (MMF; n = 414), or methotrexate (MTX; n = 322). Transplantation occurred between 2007 and 2018; CMV monitoring/management followed uniform standard practice. Hazards of CMV reactivation at various thresholds were compared. Spline curves were fit over average daily viral load and areas under the curve (AUC) within 1 year were calculated. PTCy and MMF were associated with an increased risk of early (day ≤100) CMV reactivation ≥250 IU/mL after multivariate adjustment. The viral load AUC at 1 year was highest with MMF (mean difference = 0.125 units vs MTX group) and similar between PTCy and MTX (mean difference = 0.016 units vs MTX group). CMV disease risk was similar across groups. There was no interaction between GVHD prophylaxis and CMV reactivation on chronic GVHD risk. Despite PTCy-associated increased risk of early CMV reactivation, the CMV disease risk by 1 year was low in HLA-matched PBSC transplant recipients. In contrast, MMF was associated with higher overall CMV viral burden in the 1 year posttransplant. Although different mechanisms of immunosuppressive agents may affect CMV reactivation risk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate infection risk over time.