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1.
Br J Haematol ; 204(6): 2365-2377, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577874

RESUMO

Allogeneic haematopoietic cell transplantation (allo-HCT) remains an option for tyrosine kinase inhibitor-resistant chronic myeloid leukaemia (CML) in first chronic phase (CP1) and high-risk patients with advanced disease phases. In this European Society for Blood and Marrow Transplantation (EBMT) registry-based study of 1686 CML patients undergoing first allo-HCT between 2012 and 2019, outcomes were evaluated according to donor type, particularly focusing on mismatched related donors (MMRDs). Median age at allo-HCT was 46 years (IQR 36-55). Disease status was CP1 in 43%, second CP (CP2) or later in 27%, accelerated phase in 12% and blast crisis in 18%. Donor type was matched related (MRD) in 39.2%, MMRD in 8.1%, matched unrelated (MUD) in 40.2%, and mismatched unrelated (MMUD) in 12.6%. In 4 years, overall survival (OS) for MRD, MMRD, MUD and MMUD was 61%, 56%, 63% and 59% (p = 0.21); relapse-free survival (RFS) was 48%, 42%, 52% and 46% (p = 0.03); cumulative incidence of relapse (CIR) was 33%, 37%, 27% and 30% (p = 0.07); non-relapse mortality (NRM) was 19%, 21%, 21% and 24% (p = 0.21); and graft-versus-host disease (GvHD)-free/relapse-free survival (GRFS) was 16%, 18%, 22% and 15% (p = 0.05) respectively. On multivariate analysis, MMRD use associated with longer engraftment times and higher risk of graft failure compared to MRD or MUD. There was no statistical evidence that MMRD use associated with different OS, RFS and incidence of GvHD compared to other donor types.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Pessoa de Meia-Idade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Adulto , Masculino , Feminino , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/etiologia , Transplante Homólogo , Sistema de Registros , Doadores de Tecidos , Doadores não Relacionados
2.
Am J Hematol ; 98(4): 628-638, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36606718

RESUMO

Allogeneic hematopoietic cell transplant (allo-HCT) provides the only potential route to long-term remission in patients diagnosed with blast phase transformation of myeloproliferative neoplasm (BP-MPN). We report on a large, retrospective European Society for Blood and Marrow Transplantation registry-based study of BP-MPN patients undergoing allo-HCT. BP-MPN patients undergoing first allo-HCT between 2005 and 2019 were included. A total of 663 patients were included. With a median follow-up of 62 months, the estimated 3-year overall survival (OS) was 36% (95% confidence interval [CI], 32-36). Factors associated with lower OS were Karnofsky Performance Score (KPS) <90 (hazard ratio [HR] 1.65, p < .001) and active disease at allo-HCT (HR 1.45, p < .001), whereas patients undergoing allo-HCT more recently associated with a higher OS (HR 0.96, p = .008). In a selected patient's population, the 3-year OS of patients undergoing allo-HCT in complete response (CR) and with a KPS ≥90 was 60%. KPS < 90 (HR 1.4, p = .001) and active disease (HR 1.44, p = .0004) were associated with a lower progression-free survival (PFS). Conversely, most recent allo-HCT associated with a higher PFS (HR 0.96, p = .008). Active disease at allo-HCT (HR 1.34, p = .03) was associated with a higher cumulative incidence of relapse (RI) and allo-HCT in earlier calendar years (HR 0.96, p = .02) associated with a lower RI. Last, KPS < 90 (HR 1.91, p < .001), active disease (HR 1.74, p = .003) and allo-HCT from mismatched related donors were associated with a higher non-relapse mortality (HR 2.66, p = .003). In this large series of BP-MPN patients, about one third were alive at 3 years after transplantation. Patients undergoing allo-HCT in the more recent era, with a KPS ≥90 and in CR at transplant had a better prognosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transtornos Mieloproliferativos , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Homólogo/efeitos adversos , Crise Blástica/terapia , Medula Óssea , Recidiva Local de Neoplasia/etiologia , Transtornos Mieloproliferativos/terapia , Transtornos Mieloproliferativos/etiologia , Condicionamento Pré-Transplante
3.
Am J Transplant ; 21(2): 864-869, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33037770

RESUMO

Classical veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication post allogeneic hematopoietic stem cell transplantation (HSCT). Before the recently revised EBMT criteria, the Baltimore and modified Seattle criteria failed to recognize the syndrome of late-onset VOD. We present real-world experience from a large UK transplant center reporting on VOD/SOS in consecutive HSCT adult patients (n = 530), transplanted for hematological cancers. We identified 27 patients treated with Defibrotide for VOD/SOS diagnosis, where detailed data were available for final analysis. Using standard definitions including EBMT criteria, around 30% (n = 8/27) of cases classified as late-onset VOD presenting at median of 46 (22-93) days but with D100 survival (63% vs 58%, Log-rank; P = 0.81) comparable to classical VOD. Hazard ratio for D100 mortality was 2.82 (95% CI: 1.74-4.56, P < .001, Gray test) with all VOD/SOS events. Twenty percent (n = 2/8) of late-onset VOD patients were anicteric and 42% (n = 8) classical VOD patients presented with refractory thrombocytopenia, while less than half met EBMT criteria for classical VOD in adults, highlighting gaps in real-world diagnostic limitations using EBMT criteria. However, challenges remain about underrecognition and difficulties related to early defibrotide access for treatment of late-onset VOD in current treatment guidelines. Our report strongly supports early Defibrotide for the treatment of severe VOD/SOS in adults regardless of time of onset.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Adulto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Polidesoxirribonucleotídeos , Reino Unido
4.
Transfus Apher Sci ; 59(2): 102656, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31606335

RESUMO

Thymic tumors are rare diseases with an incidence of 0.15 cases per 100,000 person-years. They can be associated with a variety of other syndromes, such as Myasthenia Gravis or autoimmune disorders. Among them, pure red cell aplasia is a hemato-pathological condition characterized by anemia, reticulocytopenia and erythroid cell hypoplasia of bone marrow. Here, we reported a case of a 62-year-old female with a long history of neurologic symptoms due to Myasthenia Gravis. She was diagnosed with thymoma, with mediastinal mass and pleural thickening. After chemoradiotherapy treatment, she was surgically resected successfully, but she developed anemia and severe thrombocytopenia, worsening in respiratory failure requiring intubation. A bone marrow biopsy was performed resulting in a red-cell aplasia with marked hypoplasia of megakaryocytopoiesis compatible with pure red cell aplasia with acquired thrombocytopenia. Considering that there are no standard treatments, clinical condition improvement was achieved only after some lines of medical treatment. Our data, together with the few already published, help to raise the attention towards acquired cytopenias and the need to optimize the treatment for a potentially life-threatening condition.


Assuntos
Aplasia Pura de Série Vermelha/diagnóstico , Trombopoese/genética , Timoma/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Doenças Raras
5.
Biol Blood Marrow Transplant ; 24(12): 2501-2508, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30041010

RESUMO

Disease relapse remains an unmet medical need for patients with Hodgkin lymphoma (HL) receiving an allogeneic hematopoietic cell transplantation (HCT). With the aim of identifying patients at high risk for post-transplant relapse, we retrospectively reviewed 41 HL patients who had received haploidentical (haplo) nonmyeloablative (NMA) HCT with high dose post-transplant cyclophosphamide (PT-Cy) for graft-versus-host (GVHD) prophylaxis. Primary refractory disease, relapse within 6 months from autologous stem cell transplantation, age, pretransplant chemotherapy, HCT comorbidity index (HCT-CI), sex mismatch, tumor burden and pretransplant fluorodeoxyglucose positron emission tomography (FDG-PET) status, assessed by Deauville score, were analyzed as variables influencing outcomes. All but 1 patient engrafted: median time to neutrophil and platelet recovery was 15 (interquartile range, 13 to 23) days and 19 (interquartile range, 12 to 28) days, respectively. Cumulative incidence of severe (grade III to IV) acute graft-versus-host disease (GVHD) and 3-year moderate-severe chronic GVHD was 2.4% and 11.8%, respectively. The 3-year overall (OS), progression free (PFS), and graft relapse-free survival (GRFS) were 75.6%, 43.9%, and 39%, respectively. On multivariate analysis, 3-year OS was significantly worse in patients with HCT-CI ≥3 (hazard ratio [HR], 5.0; 95% confidence interval [CI], 1.1 to 21.8; P = .03). Three-year relapse rate, 3-year PFS, and 3-year GRFS were significantly worse in patients with HCT-CI ≥3 (HR, 3.5; 95% CI, 1.3 to 9.3; P = .01; HR, 3.3; 95% CI, 1.2 to 9.0; P = .02; and HR, 4.2; 95% CI, 1.7 to 9.9; P = .001, respectively) and in patients with a Deauville score ≥4 on pretransplant FDG-PET (HR, 4.4; 95% CI, 1.6-12.4; P = .005, HR, 3.8; 95% CI, 1.5 to 9.7; P = .005; and 3.2; 95% CI, 1.3 to 7.9; P = .01, respectively). On univariate analysis, 3-year NRM was significantly worse only in patients with a HCT-CI ≥3 (HR, 17.6; 95% CI, 1.4 to 221.0). Among relapsed or refractory HL patients undergoing haplo NMA HCT with PT-Cy, pretransplant FDG-PET with a Deauville score ≥4 and HCT-CI ≥3 identified patients at high risk of relapse. Moreover, an HCT-CI ≥3 was associated with higher NRM and lower OS.


Assuntos
Ciclofosfamida/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/cirurgia , Imunossupressores/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Transplante Haploidêntico/métodos , Adulto , Comorbidade , Ciclofosfamida/farmacologia , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/patologia , Humanos , Imunossupressores/farmacologia , Masculino , Recidiva Local de Neoplasia
6.
Biol Blood Marrow Transplant ; 24(1): 119-126, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29024804

RESUMO

We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Ciclofosfamida/uso terapêutico , Antígenos HLA/imunologia , Histocompatibilidade/imunologia , Transplante Haploidêntico/efeitos adversos , Transplante de Medula Óssea/mortalidade , Rejeição de Enxerto/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Análise de Sobrevida , Transplante Haploidêntico/mortalidade
10.
Clin Nutr ESPEN ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971406

RESUMO

Patients undergoing allogeneic stem cell transplant (HSCT) have a higher risk of developing malnutrition. The aetiology is multifactorial and complex: the conditioning regimen causes damages to the gastrointestinal tract that can contribute to trigger graft-versus-host disease and/or infectious complications that adversely affect food intake and the gut absorption of nutrients in transplant recipients. Consequently, patients might develop weight loss and muscle wasting. There is mounting evidence that insufficient muscle mass increases the risk of toxicity to many chemotherapy drugs. Furthermore, the screening for malnutrition, assessment and intervention can vary among HSCT centers. Hereby, we report the main nutritional clinical issues in the field of HSCT and the main nutritional tools used in this setting. Future clinical trials investigating nutritional tools and dose-escalating studies based on pre-treatment body composition assessment may help having the potential to alter cancer treatment paradigms.

11.
Mediterr J Hematol Infect Dis ; 16(1): e2024002, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38223487

RESUMO

Background: Allogeneic haematopoietic stem-cell transplant is an option, potentially curative, for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Post-transplant cyclophosphamide administration allows for the selection of haploidentical donors in patients who are eligible for the procedure but do not have a fully matched donor since it can overcome the HLA barrier. There is still an active debate on whether intensifying the conditioning regimen is necessary with haploidentical donors when peripheral blood stem cells are used as the graft source. Herein, we report our decennial experience of haploidentical stem-cell transplant using peripheral blood stem cells (haplo-PBSC) at King's College Hospital. Objectives: The primary objective was to evaluate overall survival (OS) following haplo-PBSC. Secondary objectives were total OS for patients with less than two previous lines of therapy, OS according to cytomegalovirus (CMV) reactivation, incidence of transplant-related mortality (TRM), graft-versus-host disease (GVHD) and GVHD-relapse-free survival (GRFS). Results: One-year and three-year total OS were 62% and 43%, respectively, with a median OS of 22 months. One-year and three-year OS for patients with ≤2 and those with >2 previous lines of therapy were 72% and 55%, and 60% and 22%, respectively (p-value=0.04). The median OS in patients with >2 previous and ≤2 lines of therapy was 16 and 49 months, respectively. Cumulative incidence (CI) of relapse was 25% with a median time to relapse of 5 months (range 1 - 38 months). Conclusions: Haploidentical haematopoietic stem-cell transplant is potentially curative in chemosensitive AML and MDS and offers a high rate of prolonged remission. Our cohort further confirms the role of consolidative haploidentical transplant in patients in complete remission and highlights that patients with heavily pre-treated disease may not benefit from this strategy.

12.
Bone Marrow Transplant ; 59(7): 928-935, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38491198

RESUMO

We aimed to compare outcomes following treosulfan (TREO) or busulfan (BU) conditioning in a large cohort of myelofibrosis (MF) patients from the EBMT registry. A total of 530 patients were included; 73 received TREO and 457 BU (BU ≤ 6.4 mg/kg in 134, considered RIC, BU > 6.4 mg/kg in 323 considered higher dose (HD)). Groups were compared using adjusted Cox models. Cumulative incidences of engraftment and acute GVHD were similar across the 3 groups. The TREO group had significantly better OS than BU-HD (HR:0.61, 95% CI: 0.39-0.93) and a trend towards better OS over BU-RIC (HR: 0.66, 95% CI: 0.41-1.05). Moreover, the TREO cohort had a significantly better Progression-Free-Survival (PFS) than both the BU-HD (HR: 0.57, 95% CI: 0.38-0.84) and BU-RIC (HR: 0.60, 95% CI: 0.39-0.91) cohorts, which had similar PFS estimates. Non-relapse mortality (NRM) was reduced in the TREO and BU-RIC cohorts (HR: 0.44, 95% CI: 0.24-0.80 TREO vs BU-HD; HR: 0.54, 95% CI: 0.28-1.04 TREO vs BU-RIC). Of note, relapse risk did not significantly differ across the three groups. In summary, within the limits of a registry-based study, TREO conditioning may improve PFS in MF HSCT and have lower NRM than BU-HD with a similar relapse risk to BU-RIC. Prospective studies are needed to confirm these findings.


Assuntos
Bussulfano , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Sistema de Registros , Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Humanos , Mielofibrose Primária/terapia , Mielofibrose Primária/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Doença Enxerto-Hospedeiro/mortalidade
13.
Bone Marrow Transplant ; 59(3): 380-386, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38184740

RESUMO

Ruxolitinib has become the new standard of care for steroid-refractory and steroid-dependent chronic GVHD (SR-cGVHD). Our aim was to collect comparative data between ruxolitinib and extracorporeal photophoresis (ECP). We asked EBMT centers if they were willing to provide detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively and we included all patients between 1/2017-7/2019 treated with ECP or ruxolitinib for moderate or severe SR-cGVHD. We identified 84 and 57 patients with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-cGVHD (steroid dependent vs. refractory vs. intolerant to steroids). At day+180 after initiation of treatment for SR-cGVHD the odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.35 (95% CI = [0.64; 2.91], p = 0.43). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-cGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-cGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Nitrilas , Fotoferese , Pirazóis , Pirimidinas , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Esteroides/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Fotoferese/métodos , Doença Crônica , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
14.
Ann Hematol ; 92(10): 1309-18, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23686116

RESUMO

We report the final results of a prospective trial testing the combination of fludarabine, Ara-C and idarubicin (FLAI) followed by low-dose gemtuzumab ozogamicin (FLAI-GO) in 85 patients aged 60 years or more with CD33+ acute myeloid leukaemia (AML). Median age was 68 years (60-82); karyotype was unfavourable in 21 patients (24%), intermediate in 63 (74%) and favourable in 1 (2%). There were five therapy-related deaths. Of the 80 evaluable patients, 47 achieved complete response (CR) (58%); CR rates were 65 and 32% in good-intermediate/poor karyotype patients, respectively. Median length of CR was 7 months (3-76). The cumulative incidence of relapse was 84% with an actuarial survival of 50.3% at 1 year and 14.4% at 2 years. The study control population is an unselected consecutive historic cohort of 104 patients treated with the FLAI regimen, who were matched for age and prognostic factors. CR rates after FLAI-GO and FLAI were comparable. However, patients with de novo AML and intermediate-favourable karyotype receiving GO had a significantly lower risk of relapse at 2 years as compared to patients not receiving GO (n = 77) (40 vs 80%, p = 0.01) and significantly better disease-free survival (p = 0.018) and overall survival (p = 0.022).


Assuntos
Aminoglicosídeos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Citarabina/uso terapêutico , Idarubicina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Vidarabina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Gemtuzumab , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Vidarabina/uso terapêutico
15.
Transplant Cell Ther ; 29(11): 687.e1-687.e7, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37633414

RESUMO

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the sole curative option for myelofibrosis (MF). Relapse remains a significant problem, however, occurring in up to 20% to 30% of cases. Donor lymphocyte infusion (DLI) represents a potentially effective strategy for relapse prevention and management, but the optimal timing based on measurable residual disease/chimerism analyses and the choice of regimen remain undetermined. We performed a retrospective real-world analysis of a multicenter cohort of MF allo-HCT recipients from 8 European transplantation centers who received DLI between 2005 and 2022. Response was assessed using International Working Group-Myeloproliferative Neoplasms Research and Treatment-defined response criteria, and survival endpoints were estimated using the Kaplan-Meier estimator and log-rank test. The study included 28 patients with a median age of 58 years and a Karnofsky Performance Status of >80. The majority of patients had Dynamic International Prognostic Scoring System-plus intermediate-2 or high-risk disease at the time of allo-HCT. In vivo T cell depletion was used in 20 patients (71.2%), with 19 of the 20 receiving antithymocyte globulin. The indication for DLI was either "preemptive" (n = 15), due to a decrease in recipient chimerism (n = 13) or molecular relapse (n = 2), or "therapeutic" (n = 13) for clinician-defined hematologic/clinical relapse. No patient received DLI prophylactically. The median time of DLI administration was 23.4 months post allo-HCT. Of the 16 patients receiving multiple DLIs, 12 were part of a planned escalating dose regimen. The median follow-up from the time of first DLI was 55.4 months. The responses to DLI were complete response in 9 patients, partial response in 1 patient, and clinical improvement in 6 patients. Chimerism levels improved in 16 patients, and stable disease was reported in 5 patients. No response or progression was reported in 7 patients. DLI-induced acute graft-versus-host disease (aGVHD) was reported in 11 patients (39%), with grade III-IV aGVHD in 7 (25%). The median overall survival from the time of first DLI was 62.6 months, and the cumulative incidence of relapse/progression after first DLI was 30.8% at 6 months. This study highlights that good response rates can be achieved with DLI even after frank relapse in some patients in a cohort in which other treatment options are very limited. More prospective studies are warranted to identify the optimal DLI regimen and timing to improve patient outcomes.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Imunoterapia Adotiva/efeitos adversos , Mielofibrose Primária/terapia , Mielofibrose Primária/complicações , Recidiva Local de Neoplasia/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos , Recidiva
16.
Mediterr J Hematol Infect Dis ; 15(1): e2023041, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37435036

RESUMO

Background: The second decade of this millennium was characterized by a widespread availability of chimeric antigen receptor T-cell (CAR-T) therapies to treat relapsed and refractory lymphomas. As expected, the role and indication of allogeneic haematopoietic stem cell transplant (allo-HSCT) in the management of lymphoma changed. Currently, a non-neglectable proportion of patients will be considered candidate for an allo-HSCT, and the debate of which transplant platform should be offered is still active. Objectives: to report the outcome of patients affected with relapsed/refractory lymphoma and transplanted following reduced intensity conditioning at King's College Hospital, London, between January 2009 and April 2021. Methods: Conditioning was with 150mg/m2 of fludarabine and melphalan of 140mg/m2. The graft was unmanipulated G-CSF mobilized peripheral blood haematopoietic stem cells (PBSC). Graft-versus-host disease (GVHD) prophylaxis consisted of pre-transplant Campath at the total dose of 60 mg in unrelated donors and 30 mg in fully matched sibling donors and ciclosporin. Results: One-year and five years OS were 87% and 79.9%, respectively, and median OS was not reached. The cumulative incidence of relapse was 16%. The incidence of acute GVHD was 48% (only grade I/II); no cases of grade III/IV were diagnosed. Chronic GVHD occurred in 39% of patients. TRM was 12%, with no cases developed within day 100 and 18 months after the procedure. Conclusions: The outcomes of heavily pretreated lymphoma patients are favorable, with median OS and survival not reached after a median of 49 months. In conclusion, even if some lymphoma subgroups cannot be treated (yet) with advanced cellular therapies, this study confirms the role of allo-HSCT as a safe and curative strategy.

17.
Transplant Cell Ther ; 29(11): 698.e1-698.e6, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37579918

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative strategy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The prediction of transplantation-related mortality (TRM) using the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and an arbitrary upper age limit of 55 years for administering myeloablative conditioning (MAC) are common strategies to ensure a safe procedure. The use of reduced-toxicity conditioning regimens is an additional approach to providing safe and effective myeloablation. Herein we report the outcome of AML and MDS patients conditioned with fludarabine and a myeloablative dose of busulfan (FB4) stratified by age and HCT-CI score. The primary objective was overall survival (OS) for patients age ≥55 years. Secondary objectives were total OS, TRM, graft-versus-host disease (GVHD), and GVHD, relapse-free survival (GRFS). The 2 year OS was 72% in patients age <55 and 51% in patients age ≥55. In patients age ≥55 with an HCT-CI <2, the estimated 2 year OS was 64%, with median OS not reached. In those with HCT-CI ≥2, the 2-year OS was 43%, with a median OS of 14 months. The total cumulative incidence of relapse was 30% regardless of age or HCT-CI score. FB4 conditioning regimen offers a high rate of prolonged remission with a relapse rate similar to that reported in previous studies. These positive outcomes suggest that this conditioning platform can be offered to patients age ≥55 years in the absence of comorbidities, and that age should not be the sole determinant of conditioning intensity.


Assuntos
Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Pessoa de Meia-Idade , Bussulfano/uso terapêutico , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Doença Enxerto-Hospedeiro/etiologia , Recidiva , Linfócitos T
18.
Front Immunol ; 14: 1283034, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149251

RESUMO

Introduction: Extracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making. Methods: We asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. Results: 31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. Discussion: The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Esteroides/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia
19.
Hematol Rep ; 14(3): 213-221, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35893153

RESUMO

Herein, we present a case of cytomegalovirus (CMV) colitis that occurred after two cycles of azacitidine and venetoclax in a 64-year-old woman affected with acute myeloid leukaemia (AML) secondary to a previous diagnosis of a hypoplastic myelodysplastic syndrome (hypo-MDS). This patient never had detectable CMV viraemia, and there was no evidence of immune deficiency that could justify this opportunistic infection. Additionally, this is most likely the first report describing CMV colitis in a patient treated upfront with azacitidine and venetoclax.

20.
EJHaem ; 3(1): 215-217, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35846212

RESUMO

During the COVID-19 pandemic, access to health services has been considerably restricted and furthermore, patients have been reluctant to attend for routine monitoring, and this may have had a negative impact in the management of patients affected with haematological disorders. Sudden blast crisis in chronic myeloid leukaemia is categorized as a rapid onset of blastic phase, after a documented 'optimal' response to tyrosine kinase inhibitor (TKI) therapy and within 3 months of a normal complete blood count. Herein, we describe a case of patient who developed sudden blast crisis after TKI while in treatment-free remission.

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