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1.
Leuk Lymphoma ; 61(1): 18-26, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31452423

RESUMO

Adolescents and young adults (AYAs) with ALL represent a unique population in terms of their biology and treatment. Studies have demonstrated an improved outcome when these patients are treated with pediatric-inspired regimens. Novel antibody based therapies have demonstrated impressive results in relapsed/refractory B-ALL and are starting to be evaluated in the upfront setting. Immunotherapy with CAR T cells had great success in ALL and clinical trials are ongoing and further studies are being done to expand access to this therapy and decrease toxicities. Although our outcomes with this disease have improved significantly, transplant still plays a role for high risk patients in CR1 (based on MRD status) and for patients with relapsed/refractory ALL.

2.
Biol Blood Marrow Transplant ; 26(3): e65-e73, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31830528

RESUMO

Prolonged thrombocytopenia after hematopoietic stem cell transplantation (HSCT) is a strong risk factor for transplantation-related morbidity and mortality, and no standard treatment guideline exists. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, increases the platelet production, and are being increasingly used in various conditions with thrombocytopenia. In this review, we present an overview of these TPO-RAs and review their efficacy and safety in prolonged post-HSCT thrombocytopenia. Through a systematic literature search, we identified 25 reports describing their use for this indication. Thirteen reports (8 case series and 5 case reports) described the use of eltrombopag in 78 patients with prolonged isolated thrombocytopenia (PIT) and 43 patients with secondary failure of platelet recovery (SFPR). A consistent and durable response with a rise in platelet counts >50 × 10 9/L for 7 consecutive days without platelet transfusion was seen in 85 of 121 patients (overall response rate [ORR], 70%). The responders included 56 patients with PIT (ORR for PIT, 72%) and 29 patients with SFPR (ORR for SFPR, 67%). No serious grade 3 or 4 adverse effects were reported. Similarly, 12 reports (6 case series and 6 case reports) described the use of romiplostim in prolonged post-HSCT thrombocytopenia (in 17 patients with PIT and 32 patients with SFPR). Response with the increment of platelet count was described in 40 out of 49 patients (ORR, 82%). Among the responders, 10 patients had PIT (ORR for PIT, 59%) and 30 patients had SFPR (ORR for SFPR, 94%). Our data show that TPO-RAs have an overall favorable response rate for both PIT and SFPR with a reasonable safety profile. However, given the lack of control groups, study heterogeneity, and the potential publication bias, these results should be interpreted with caution.

3.
Hematol Oncol Stem Cell Ther ; 13(1): 32-39, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31881183

RESUMO

OBJECTIVE/BACKGROUND: Cytomegalovirus (CMV) infection and disease are common infectious complications after allogeneic hematopoietic cell transplantation (alloHCT). Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is a ligand of the natural killer (NKG2D) receptor on immune effector cells that helps mediate NK cell alloreactivity. We hypothesized that MICA polymorphisms may influence CMV infection and disease incidence after alloHCT. METHODS: We conducted a retrospective analysis of 423 adults at the Cleveland Clinic with hematologic malignancies treated with a matched related or unrelated donor alloHCT. CMV cases analyzed included a compositive of instances of viral copy replication above detection limits as well as any biopsy-proven tissue invasive disease episodes. Genotypes at the MICA-129 position have been categorized as weak (valine/valine; V/V), intermediate (methionine/valine; M/V), or strong (methionine/methionine; M/M) receptor affinity. RESULTS: In multivariable analysis, V/V donor MICA-129 genotype was associated with CMV infection and disease (hazard ratio [HR] = 1.40; 95% confidence interval [CI], 1.00-1.96; p = .05), but not MICA mismatch (HR = 1.38; 95% CI, 0.83-2.29; p = .22). There was no association of acute or chronic GVHD with MICA donor-recipient mismatch (HR = 1.05; 95% 95% CI, 0.66-1.68; p = .83 and HR = 0.94; 95% CI, 0.51-1.76; p = .85, respectively) or V/V donor MICA-129 genotypes (HR = 1.02; 95% CI, 0.79-1.31; p = .89 and HR = 0.89; 95% CI, 0.65-1.22; p = .47, respectively). CONCLUSION: These findings suggest that the donor MICA-129 V/V genotype with weak NKG2D receptor binding affinity is associated with an increased risk of CMV infection and disease after alloHCT.

4.
Br J Haematol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713857

RESUMO

Beginning early in childhood, patients with sickle cell disease [SCD; a group of genetic haemoglobin disorders characterized by the sickle or HbS mutation (HBB E7V)] are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, haematopoietic cell transplantation (HCT), a curative therapy for SCD, remains underutilized. A variety of factors, including the limited availability of suitable donors, play a role in this trend, but do not fully explain the low frequency with which this therapy is employed. The objective of this study was to identify paediatric haematologists' attitudes about HCT as a treatment option for SCD, and to describe the impact of these attitudes on their practices of discussing HCT with families of children affected by this disease. A nationwide survey of paediatric haematologists in the United States was conducted between February and May 2016. Two hundred and eighty-seven surveys were included in the final analysis (response rate 20%). On average, respondents reported informing 42% of families about HCT as a treatment option (N = 248, 95% confidence interval: 38-46). Clinician attitudes about the cost and safety of HCT were associated with practices of discussing this therapy with families. These findings suggest that clinician attitudes and referral practices may play a role in the underutilization of this therapy in the SCD population.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31628924

RESUMO

OBJECTIVE/BACKGROUND: Busulfan/cyclophosphamide (Bu/Cy) and busulfan/fludarabine (Bu/Flu) are both standard myeloablative conditioning (MAC) regimens for allogeneic hematopoietic cell transplantation (alloHCT). We compared the effectiveness of these regimens with a focus on quality of life (QOL). METHODS: This was a single center, retrospective analysis of adult acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients who underwent a first T-cell replete HLA-8/8 matched related or unrelated donor alloHCT. Patients received a myeloablative regimen of either parenteral Bu/Cy or Bu/Flu. Outcomes assessed included infections, graft-versus-host-disease (GVHD), relapse, relapse mortality (RM), relapse-free survival (RFS), nonrelapse mortality (NRM), overall survival (OS), and QOL. RESULTS: From 2008 to 2017, 126 AML and 84 MDS adult patients age ≥18 years were identified meeting inclusion criteria. In terms of QOL, there were no significant differences between Bu/Cy and Bu/Flu cohorts in the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) scores or mucositis severity for either AML or MDS patients. Amongst AML patients, those receiving Bu/Flu had more rapid neutrophil and platelet recovery and a shorter length of hospital stay (LOS); there were no differences in the other posttransplant outcomes. Similarly, amongst MDS patients, those receiving Bu/Flu had more rapid platelet recovery and a shorter LOS as well as more CMV infections, but less NRM and no differences in other outcomes. CONCLUSION: We confirmed that myeloablative Bu/Flu conditioning has comparable clinical and QOL outcomes to Bu/Cy.

6.
Blood Adv ; 3(18): 2732-2737, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31530545

RESUMO

Volatile organic compounds (VOCs) are generated during pathologic processes, and their assessment can be used to diagnose and monitor a variety of diseases. Given the role of the microbiome in graft-versus-host disease (GVHD), we hypothesized that microorganisms producing volatile metabolites may alter VOCs expelled in breath in patients with gastrointestinal (GI) GVHD. In this pilot study, exhaled breath samples were obtained from 19 patients with grade 2 to 4 acute GI GVHD, 10 patients with no GVHD at day 100, and 10 healthy control subjects; the samples were analyzed by using mass spectrometry. Overall, nine (47%) patients had grade 2 GVHD, eight (42%) patients had grade 3 GVHD, and two (11%) patients had grade 4 GVHD; 26% had upper GI, 21% had lower GI, and 53% had both upper and lower GI manifestations. Stepwise canonical discriminant analysis identified 5 VOCs distinguishing patients with and without GI GVHD: 2-propanol, acetaldehyde, dimethyl sulfide, isoprene, and 1-decene (Wilks' Λ, 0.43; F statistic, 6.08; P = .001). The model correctly classified 89% (17 of 19) and 90% (9 of 10) of patients with and without GI GVHD, respectively. Breath analysis is a feasible and promising noninvasive method to detect acute GI GVHD. Further study of serial breath analysis and the gut microbiome in a larger cohort are ongoing to validate these findings.

7.
Biol Blood Marrow Transplant ; 25(12): 2522-2526, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31525493

RESUMO

Autologous hematopoietic cell transplantation (AHCT) is standard therapy for patients with chemosensitive, relapsed, diffuse large B cell lymphoma (DLBCL). We performed a retrospective cohort study to delineate subsequent (conditional) and relative survival in 371 adult patients with DLBCL who underwent AHCT between 2000 and 2014 and had survived for 1, 2, 3, or 5 years after transplant. The probability of overall survival at 10 years after AHCT was 62%, 71%, 77%, and 86%, respectively, for the 4 cohorts, whereas that of progression-free survival (PFS) was 55%, 65%, 72%, and 81%, respectively. The respective cumulative incidence of nonrelapse mortality (NRM) at 10 years after transplantation was 13%, 12%, 11%, and 8%, respectively. In multivariable analysis, older age was associated with greater mortality risk among all but 5-year survivors; relapse within the landmark time was associated with greater mortality risk in all groups. Older age and relapse within the landmark time were associated with worse PFS in all groups. Standardized mortality ratio (SMR) was significantly higher than an age-, gender-, and race-matched general population, with the magnitude of SMR decreasing as the landmark time increased (4.0 for 1-year, 3.0 for 2-year, 2.4 for 3-year, and 1.8 for 5-year survivors). Our study provides information on long-term survival and prognosis that will assist in counseling patients with DLBCL who have received AHCT. Survival improves with longer time in remission post-transplant, although patients continue to remain at risk for NRM, underscoring the need for continued vigilance and prevention of late complications.

8.
Blood Adv ; 3(17): 2562-2570, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31471325

RESUMO

We studied 1110 patients with ß-thalassemia major aged ≤25 years who received transplants with grafts from HLA-matched related (n = 677; 61%), HLA-mismatched related (n = 78; 7%), HLA-matched unrelated (n = 252; 23%), and HLA-mismatched unrelated (n = 103; 9%) donors between 2000 and 2016. Ninety percent of transplants were performed in the last decade. Eight-five percent of patients received ≥20 transfusions and 88% were inadequately chelated. All patients received myeloablative-conditioning regimen. Overall and event-free survival were highest for patients aged ≤6 years and after HLA-matched related and HLA-matched unrelated donor transplantation. The 5-year probabilities of overall survival for patients aged ≤6 years, 7 to 15 years, and 16 to 25 years, adjusted for donor type and conditioning regimen were 90%, 84%, and 63%, respectively (P < .001). The corresponding probabilities for event-free survival were 86%, 80%, and 63% (P < .001). Overall and event-free survival did not differ between HLA-matched related and HLA-matched unrelated donor transplantation (89% vs 87% and 86% vs 82%, respectively). Corresponding probabilities after mismatched related and mismatched unrelated donor transplantation were 73% vs 83% and 70% vs 78%. In conclusion, if transplantation is considered as a treatment option it should be offered early (age ≤6 years). An HLA-matched unrelated donor is a suitable alternative if an HLA-matched relative is not available.

9.
Pediatr Transplant ; 23(6): e13520, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31209983

RESUMO

The outcome of allogeneic HCT in patients previously infected with HCV is a widely debated topic and rarely reported in the pediatric and young adult age group given the small population of affected patients. New medications directly targeting HCV have induced virologic cures for over 90% of patients, and their use in the pretransplant setting may improve outcomes for patients infected with HCV. We describe two patients with transfusion-dependent beta-thalassemia major who underwent matched sibling donor bone marrow transplantation, one with a myeloablative regimen and one with a reduced-intensity conditioning regimen. Allogeneic HCT appears feasible in patients with HCV infection that clear viremia prior to conditioning therapy and with a reduced-intensity conditioning regimen. Further investigation is warranted to better define transplant risks in this population.

10.
Haematologica ; 104(10): 1974-1983, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30948484

RESUMO

Quality of response to immunosuppressive therapy and long-term outcomes for pediatric severe aplastic anemia remain incompletely characterized. Contemporary evidence to inform treatment of relapsed or refractory severe aplastic anemia for pediatric patients is also limited. The clinical features and outcomes for 314 children treated from 2002 to 2014 with immunosuppressive therapy for acquired severe aplastic anemia were analyzed retrospectively from 25 institutions in the North American Pediatric Aplastic Anemia Consortium. The majority of subjects (n=264) received horse anti-thymocyte globulin (hATG) plus cyclosporine (CyA) with a median 61 months follow up. Following hATG/CyA, 71.2% (95%CI: 65.3,76.6) achieved an objective response. In contrast to adult studies, the quality of response achieved in pediatric patients was high, with 59.8% (95%CI: 53.7,65.8) complete response and 68.2% (95%CI: 62.2,73.8) achieving at least a very good partial response with a platelet count ≥50×109L. At five years post-hATG/CyA, overall survival was 93% (95%CI: 89,96), but event-free survival without subsequent treatment was only 64% (95%CI: 57,69) without a plateau. Twelve of 171 evaluable patients (7%) acquired clonal abnormalities after diagnosis after a median 25.2 months (range: 4.3-71 months) post treatment. Myelodysplastic syndrome or leukemia developed in 6 of 314 (1.9%). For relapsed/refractory disease, treatment with a hematopoietic stem cell transplant had a superior event-free survival compared to second immunosuppressive therapy treatment in a multivariate analysis (HR=0.19, 95%CI: 0.08,0.47; P=0.0003). This study highlights the need for improved therapies to achieve sustained high-quality remission for children with severe aplastic anemia.

11.
Br J Haematol ; 185(5): 935-939, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30891747

RESUMO

Compound heterozygous germline mutations in CTC1 gene have been found in patients with atypical dyskeratosis congenita (DC), whereas heterozygous carriers are unaffected. Through screening of a large cohort of adult patients with acquired bone marrow failure syndromes, in addition to a DC case, we have also found extremely rare or novel heterozygous deleterious germline variants of CTC1 in patients with aplastic anaemia (AA; n = 5), paroxysmal nocturnal haemoglobinuria (PNH; n = 3) and myelodysplastic syndrome (MDS; n = 2). A compound heterozygous case of AA showed clonal evolution. Our results suggest that some of the inherited CTC1 variants may represent predisposition factors for acquired bone marrow failure.

12.
Health Commun ; : 1-5, 2019 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-30907145

RESUMO

Time is quite possibly a physician's most valuable asset, yet the tendency of almost all physicians is to be overly committed. How do we slowdown and make a meaningful difference? Virtual visits provide a new way to share and care without sacrificing the important nuances of face-to-face communication. When the Cleveland Clinic expanded our Distance Health capabilities in 2017 using virtual visits, we began a successful journey which provides cancer patients and their caregivers a new type of expert, unrushed cancer care access. This essay describes our current process for providing virtual visit access, preparing prior to the visit, keeping the visit as informative a possible, and closing the visit with a "distance health encounter" in the electronic medical record coupled with a summary and additional information via email.

13.
J Pediatr Hematol Oncol ; 41(3): 187-193, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30789459

RESUMO

Beginning early in childhood, patients with sickle cell disease (SCD) are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, hematopoietic cell transplantation (HCT), a curative treatment for SCD, remains underutilized. In the literature there is a paucity of data concerning medical decision maker (MDM) awareness of HCT as a treatment option for SCD. The objective of this study was to estimate the proportion of parents/guardians of children with SCD who are aware of HCT as a treatment option, and to identify the demographic factors associated with knowledge of this therapy's curative potential. Between November 2015 and December 2016, 327 parents/guardians were surveyed across 4 clinical sites in 3 Midwestern US cities. Although 82% of parents/guardians had heard of HCT in the past and 78% were aware of the therapy's curative potential, nearly half indicated that they did not know whether HCT could specifically cure their child of the disease. Respondents who had discussed HCT with their child's physician had 5 times higher odds of being aware of HCT's curative potential than those who had not. These findings suggest that additional efforts to enhance MDM knowledge of HCT as well as shared decision making in the use of this therapy, is warranted.


Assuntos
Anemia Falciforme/terapia , Transplante de Células-Tronco Hematopoéticas , Conhecimento , Tutores Legais , Pais , Adulto , Criança , Feminino , Comunicação em Saúde , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Inquéritos e Questionários , Estados Unidos
14.
Bone Marrow Transplant ; 54(8): 1281-1286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30655603

RESUMO

Next generation sequencing (NGS) has become an important tool to inform disease risk for myeloid malignancies, however data remains conflicting regarding the significance of individual mutations. We performed targeted NGS on 112 patients with AML, and 80 with MDS, who underwent allogeneic hematopoietic cell transplantation. The most common mutations in AML were TET2 (14.7%), FLT3 (12.9%), DNMT3A (12.1%), and RUNX1 (7.8%). Complex cytogenetics (HR 2.82, P = .017) and disease status (33% were associated with poor RFS (HR 3.57, P = .017; and HR 6.57, P = .003; respectively). Molecular profiling is increasingly important in the care of patients with AML and MDS. Further studies are needed to understand the molecular complexities, including the significance of clonal burden, to better inform care decisions.

15.
Bone Marrow Transplant ; 54(5): 775-781, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30375493

RESUMO

Donor-derived T-cells mediate graft-versus-leukemia effect, immune reconstitution, and graft-versus-host-disease (GvHD) after allogeneic hematopoietic cell transplantation (HCT). We examined the association of donor cell subsets with outcomes in recipients of myeloablative allogeneic HCT using bone marrow (BM, N = 359) grafts from 2002 to 2014 with related or unrelated donors. Analysis considered pre-infusion graft total nucleated cell (TNC), CD34+ CD3+, CD4+, CD8+ doses. Most patients received busulfan-cyclophosphamide or etoposide-total body irradiation conditioning for acute leukemia or myelodysplastic syndrome. Calcineurin inhibitor-mycophenolate mofetil (CNI-MMF) (49%) or calcineurin inhibitor-methotrexate (CNI-MTX) (47%) were used for GvHD prophylaxis. In multivariable analysis, higher CD34+ dose was associated with platelet engraftment (P < 0.001) and lymphocyte recovery (P = 0.006). There was no association of donor cell subsets with donor chimerism or overall survival. In conclusion, BM graft composition is associated with myeloablative allogeneic HCT outcomes and future studies to evaluate optimal graft composition are needed.

16.
J Clin Oncol ; 37(5): 367-374, 2019 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-30523748

RESUMO

PURPOSE: Increasing the number of hematopoietic stem and progenitor cells within an umbilical cord blood (UCB) graft shortens the time to hematopoietic recovery after UCB transplantation. In this study, we assessed the safety and efficacy of a UCB graft that was expanded ex vivo in the presence of nicotinamide and transplanted after myeloablative conditioning as a stand-alone hematopoietic stem-cell graft. METHODS: Thirty-six patients with hematologic malignancies underwent transplantation at 11 sites. RESULTS: The cumulative incidence of neutrophil engraftment at day 42 was 94%. Two patients experienced secondary graft failure attributable to viral infections. Hematopoietic recovery was compared with that observed in recipients of standard UCB transplantation as reported to the Center for International Blood and Marrow Transplant Research (n = 146). The median time to neutrophil recovery was 11.5 days (95% CI, 9 to 14 days) for recipients of nicotinamide-expanded UCB and 21 days (95% CI, 20 to 23 days) for the comparator ( P < .001). The median time to platelet recovery was 34 days (95% CI, 32 to 42 days) and 46 days (95% CI, 42 to 50 days) for the expanded and the comparator cohorts, respectively ( P < .001). The cumulative incidence of grade 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 44%, and grade 3 and 4 acute GVHD at day 100 was 11%. The cumulative incidence at 2 years of all chronic GVHD was 40%, and moderate/severe chronic GVHD was 10%. The 2-year cumulative incidences of nonrelapse mortality and relapse were 24% and 33%, respectively. The 2-year probabilities of overall and disease-free survival were 51% and 43%, respectively. CONCLUSION: UCB expanded ex vivo with nicotinamide shortens median neutrophil recovery by 9.5 days (95% CI, 7 to 12 days) and median platelet recovery by 12 days (95% CI, 3 to 16.5 days). This trial establishes feasibility, safety, and efficacy of an ex vivo expanded UCB unit as a stand-alone graft.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Sangue Fetal/efeitos dos fármacos , Neoplasias Hematológicas/terapia , Niacinamida/farmacologia , Adolescente , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Intervalo Livre de Doença , Feminino , Sangue Fetal/citologia , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Neutrófilos/imunologia , Condicionamento Pré-Transplante/métodos , Adulto Jovem
18.
Blood ; 132(13): 1438-1451, 2018 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-29997222

RESUMO

Allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning for disorders associated with excessive inflammation such as hemophagocytic lymphohistiocytosis (HLH) is associated with early mortality. A multicenter prospective phase 2 trial of reduced-intensity conditioning with melphalan, fludarabine, and intermediate-timing alemtuzumab was conducted for HLA matched or single HLA locus mismatched related or unrelated donor HCT in a largely pediatric cohort. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine with methylprednisolone. The primary end point was 1-year overall survival (OS). Thirty-four patients with HLH and 12 with other primary immune deficiencies were transplanted. With a median follow-up of 20 months, the 1-year OS for transplanted patients was 80.4% (90% confidence interval [CI], 68.6%-88.2%). Five additional deaths by 16 months yielded an 18-month OS probability of 66.7% (90% CI, 52.9%-77.3%). Two patients experienced primary graft failure, and 18 patients either experienced a secondary graft failure or required a second intervention (mostly donor lymphocyte infusion [DLI]). At 1 year, the proportion of patients alive with sustained engraftment without DLI or second HCT was 39.1% (95% CI, 25.2%-54.6%), and that of being alive and engrafted (with or without DLI) was 60.9% (95% CI, 45.4 %-74.9%). The day 100 incidence of grade II to IV acute GVHD was 17.4% (95% CI, 8.1%-29.7%), and 1-year incidence of chronic GVHD was 26.7% (95% CI, 14.6%-40.4%). Although the trial demonstrated low early mortality, the majority of surviving patients required DLI or second HCT. These results demonstrate a need for future approaches that maintain low early mortality with improved sustained engraftment. The trial was registered at Clinical Trials.gov (NCT 01998633).


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfo-Histiocitose Hemofagocítica/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Alemtuzumab/uso terapêutico , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Masculino , Melfalan/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto Jovem
19.
Biol Blood Marrow Transplant ; 24(8): 1651-1656, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29753157

RESUMO

This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (range, 1 to 19) underwent allogeneic HCT for AML in first (n = 18), second (n = 11), and third or greater remission (n = 3) or MDS (n = 8) using bone marrow (n = 25), peripheral blood stem cells (n = 5), or cord blood (n = 9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2/day (BSA ≤ .5 m2), 12 g/m2/day (BSA > .5 to 1.0 m2), or 14 g/m2/day (BSA > 1.0 m2) on days -6 to -4; fludarabine 30 mg/m2/day on days -6 to -2; and a single fraction of 200 cGy total body irradiation on day -1. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and methotrexate for marrow and peripheral blood stem cell and cyclosporine/mycophenolate mofetil for cord blood. One-year overall survival, disease-free survival, and nonrelapse mortality were 80%, 73%, and 3%, respectively. One-year relapse was 38% for AML and 13% for MDS. No serious organ toxicities were observed. All 37 assessable patients engrafted. Cumulative incidences of grades II to IV acute GVHD and chronic GVHD were 22% and 40%, respectively. BSA-based treosulfan dosing resulted in predictable area under the curve and maximum concentration, which is required for dosing without measuring individual pharmacokinetic parameters. Observed differences in pharmacokinetics did not impact disease control or regimen toxicity. This BSA-based treosulfan regimen resulted in excellent engraftment and disease-free survival and minimal toxicity and transplant-related mortality (3%) in children and young adults with AML and MDS.


Assuntos
Bussulfano/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Irradiação Corporal Total , Adolescente , Bussulfano/administração & dosagem , Bussulfano/uso terapêutico , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Leucemia Mieloide Aguda/mortalidade , Masculino , Síndromes Mielodisplásicas/mortalidade , Análise de Sobrevida , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto Jovem
20.
Biol Blood Marrow Transplant ; 24(5): 1029-1034, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29369800

RESUMO

Although day +100 survival among allogeneic hematopoietic cell transplantation (HCT) recipients has improved over time, longer-term survival remains a challenge. The aim of this study was to identify prognostic factors for survival among patients surviving longer than 100 days using baseline characteristics and factors identified within the first 100 days after transplantation. Of 413 patients undergoing a first allogeneic HCT between 2006 and 2014, 335 survived >100 days post-transplantation. The majority underwent a myeloablative transplantation (75%) with a bone marrow (BM) (52%) graft source. One-year all-cause mortality (ACM) was 29%, with 16% relapse mortality (RM) and 12% nonrelapse mortality. In multivariable analysis, high-risk disease (hazard ratio [HR], 1.55; P = .003), non-cytomegalovirus infection (HR, 1.79; P = .003), more days hospitalized (HR, 1.16; P < .001), and relapse (HR, 4.38; P < .001) within the first 100 days were associated with increased risk of ACM. Patients with higher income (HR, .89; P = .024) and those who received BM (HR, .52; P < .001) or umbilical cord blood (HR, .40; P = .002) relative to peripheral blood stem cells had lower risk of ACM. Our study identifies risk factors for adverse long-term survival in 100-day survivors, a time point when patients frequently are discharged from transplantation centers. In addition to disease- and transplantation-related factors, low socioeconomic status was associated with worse long-term survival, highlighting the need for focused efforts to improve outcomes in vulnerable patient populations.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Prognóstico , Sobreviventes , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Recidiva , Classe Social , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Transplante Homólogo/mortalidade
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