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1.
Lancet Haematol ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704263
2.
Blood Adv ; 3(19): 2836-2844, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31582392

RESUMO

In the absence of prospective studies that examine the effect of conditioning regimen intensity after T-cell-replete haploidentical transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS), a retrospective cohort analysis was performed. Of the 1325 eligible patients (AML, n = 818; ALL, n = 286; and MDS, n = 221), 526 patients received a myeloablative regimen and 799 received a reduced-intensity regimen. Graft-versus-host disease prophylaxis was uniform with posttransplant cyclophosphamide, a calcineurin inhibitor, and mycophenolate mofetil. The primary end point was disease-free survival. Cox regression models were built to study the effect of conditioning regimen intensity on transplant outcomes. For patients aged 18 to 54 years, disease-free survival was lower (hazard ratio [HR], 1.34; 42% vs 51%; P = .007) and relapse was higher (HR, 1.51; 44% vs 33%; P = .001) with a reduced-intensity regimen compared with a myeloablative regimen. Nonrelapse mortality did not differ according to regimen intensity. For patients aged 55 to 70 years, disease-free survival (HR, 0.97; 37% vs 43%; P = .83) and relapse (HR, 1.32; 42% vs 31%; P = .11) did not differ according to regimen intensity. Nonrelapse mortality was lower with reduced-intensity regimens (HR, 0.64; 20% vs 31%; P = .02). Myeloablative regimens are preferred for AML, ALL, and MDS; reduced-intensity regimens should be reserved for those unable to tolerate myeloablation.

3.
Blood Adv ; 3(20): 3123-3131, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31648332

RESUMO

Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.

4.
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.

5.
Lancet Haematol ; 6(11): e585-e596, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495699

RESUMO

BACKGROUND: Donors other than matched siblings and low-intensity conditioning regimens are increasingly used in haematopoietic stem cell transplantation. We aimed to compare the relative risk of donor type and conditioning regimen intensity on the transplantation outcomes of in patients with sickle cell disease. METHODS: For this retrospective cohort study, we collected data from 90 US centres reported to the Center for International Blood and Marrow Transplant Research. Eligible patients were younger than 50 years, had genetically confirmed sickle cell disease (Hb SS) or sickle beta thalassemia (Hb Sß), and underwent allogeneic haematopoietic cell transplantation between Jan 15, 2008, and Dec 28, 2017. We considered transplants from donor-recipient pairs matched at the allele-level (HLA-A, HLA-B, HLA-C, and HLA-DRB1), including HLA-matched sibling donors, haploidentical related donors, matched unrelated donors, or mismatched unrelated donors. The main outcome was event-free survival. The effect of donor type, conditioning regimen intensity (myeloablative, non-myeloablative, and reduced-intensity regimens), age (≤12 or 13-49 years), sex, performance score, comorbidity index, recipient cytomegalovirus serostatus, graft type (bone marrow, peripheral blood, or umbilical cord blood), and transplantation period (2008-12 and 2013-17) on outcomes was studied using Cox regression models. FINDINGS: Of 996 patients with sickle cell disease and who underwent transplantation in 2008-17, 910 (91%) were included (558 [61%] patients had HLA-matched sibling donors, 137 [15%] haploidentical related donors, 111 [12%] matched unrelated donors, and 104 [11%] mismatched unrelated donors). The median follow-up was 36 months (IQR 18-60) after transplantation from HLA-matched siblings, 25 months (12-48) after transplantation from haploidentical related donors, 37 months (23-60) after transplantation from HLA-matched unrelated donors, and 47 months (24-72) after transplantation from mismatched unrelated donors. Event-free survival was worse in recipients aged 13 years or older than in those younger than 13 years (hazard ratio 1·74, 95% CI 1·24-2·45; p=0·0014) and in those who received a transplant from haploidentical related donors (5·30, 3·17-8·86; p<0·0001), matched unrelated donors (3·71, 2·39-5·75; p<0·0001), and mismatched unrelated donors (4·34, 2·58-7·32; p<0·0001) than in patients who received a transplant from matched siblings. There was no significant difference in event-free survival between recipients of transplants from non-sibling donors: haploidentical related donors (1·43, 0·81-2·50; p=0·21) or mismatched unrelated donors (1·17, 0·67-2·05; p=0·58) versus HLA-matched unrelated donors, or mismatched unrelated donors versus haploidentical related donors (1·22, 0·65-2·27; p=0·98). Event-free survival was also worse in patients conditioned with reduced-intensity regimens (1·97, 1·15-3·36; p=0·013) than in those conditioned with non-myeloablative regimens, but did not differ between those who received myeloablative compared with non-myeloablative regimens (1·57, 0·95-2·61; p=0·079). Interpretation Our data suggest that event-free survival is improved in patients with sickle cell disease who receive an allogenic transplantation at age 12 years or younger and those with an HLA-matched sibling donor. For patients without a matched sibling available for transplantation, our data do not favour one alternative donor type over another in this setting. FUNDING: National Institutes of Health and US Health Services Research Administration, Department of Health and Human Services.


Assuntos
Anemia Falciforme/terapia , Transplante de Medula Óssea , Sangue Fetal/transplante , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Anemia Falciforme/mortalidade , Anemia Falciforme/patologia , Doadores de Sangue , Transplante de Medula Óssea/efeitos adversos , Criança , Feminino , Doença Enxerto-Hospedeiro/etiologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
6.
Blood ; 134(12): 924-934, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31292117

RESUMO

Allogeneic hematopoietic cell transplantation involves consideration of both donor and recipient characteristics to guide the selection of a suitable graft. Sufficient high-resolution donor-recipient HLA match is of primary importance in transplantation with adult unrelated donors, using conventional graft-versus-host disease prophylaxis. In cord blood transplantation, optimal unit selection requires consideration of unit quality, cell dose and HLA-match. In this summary, the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research, jointly with the NMDP Histocompatibility Advisory Group, provide evidence-based guidelines for optimal selection of unrelated donors and cord blood units.

7.
Haematologica ; 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101756

RESUMO

We sought to study whether survival after haplo-identical transplantation is comparable to that after matched unrelated donor transplantation for 822 patients aged 50-75 years with acute myeloid leukemia in first or second complete remission. One hundred and ninety-two patients received grafts from haplo-identical donors (sibling 25%; offspring 75%) and 631 patients from matched unrelated donors aged 18-40 years. Patient and disease characteristics of the two groups were similar except recipients of matched unrelated donor transplantation were more likely to have poor risk cytogenetics and more likely to receive myeloablative conditioning regimens. Time from documented remission to transplant did not differ by donor type. Five-year overall survival was 32% and 42% after haplo-identical and matched unrelated donor transplant, respectively (p-value=0.1). Multivariable analysis showed higher mortality (hazard ratio 1.27, p-value=0.04) and relapse (hazard ratio 1.32, p-value=0.04) after haplo-identical transplantation, with similar non-relapse mortality risks. Chronic graft-versus-host disease was higher after matched unrelated donor compared to haplo-identical transplantation when bone marrow was the graft (hazard ratio 3.12, p-value<0.001), but when the graft was peripheral blood the risk of chronic graft-versus-host disease did not differ by donor type. These data support matched unrelated donor transplant with donors younger than 40 years is preferred.

8.
Blood Adv ; 3(3): 360-369, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30723110

RESUMO

This study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD-) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)-based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD-, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD-. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD-. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.

10.
Biol Blood Marrow Transplant ; 25(5): e174-e178, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30639825

RESUMO

Stroke and cognitive decline are hallmarks of sickle cell disease (SCD). The natural history of SCD predicts progressive loss of 1 IQ point per year attributable to disease-related pathology. Hematopoietic cell transplantation (HCT) is curative by reverting to donor-derived erythropoiesis, but evidence that HCT can positively influence disease-induced cognitive decline is lacking. The Sickle Cell Unrelated Transplant Trial prospectively evaluated cognition and brain magnetic resonance imaging (MRI) findings at 2 years after reduced-intensity conditioning followed by unrelated donor HCT. Thirteen study participants completed pre-HCT and post-HCT assessments of intelligence. The mean age of participants was 12.5 ± 3.3 years (range, 6.7 to 17.4 years). Eleven of the 13 recipients completed imaging studies at baseline and post-HCT. Seven had overt stroke pre-HCT, and 1 had an elevated transcranial Doppler velocity with abnormal MRI. The mean Full-Scale IQ was stable: 90.9 ± 13 at baseline and 91.2 ± 13 post-HCT. The mean Performance IQ was 89.9 ± 13 at baseline versus 90.9 ± 13 post-HCT, and mean Verbal IQ was 93.4 ± 13 at baseline versus 93.2 ± 13 post-HCT, respectively. Six recipients had stable MRI; 2 showed resolution of all areas of infarction. Three had additional infarcts post-HCT noted at the 2-year time point. This is the first report describing stabilization of IQ and central nervous system outcomes after unrelated donor HCT despite previous central nervous system morbidity and post-HCT posterior reversible encephalopathy syndrome. These preliminary results post-HCT suggest that HCT may stabilize the cognitive decline of SCD and should continue to be followed over the long term.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30244103

RESUMO

Children with acute leukemia who relapse after hematopoietic cell transplantation (HCT) have few therapeutic options. We studied 251 children and young adults with acute myelogenous or lymphoblastic leukemia who underwent a second HCT for relapse after their first HCT. The median age at second HCT was 11 years, and the median interval between first and second HCT was 17 months. Most of the patients (n = 187; 75%) were in remission, received a myeloablative conditioning regimen (n = 157; 63%), and underwent unrelated donor HCT (n = 230; 92%). The 2-year probability of leukemia-free survival (LFS) was 33% after transplantation in patients in remission, compared with 19% after transplantation in patients not in remission (P = .02). The corresponding 8-year probabilities were 24% and 10% (P = .003). A higher rate of relapse contributed to the difference in LFS. The 2-year probability of relapse after transplantation was 42% in patients in remission and 56% in those in relapse (P = .05). The corresponding 8-year probabilities were 49% and 64% (P = .04). These data extend the findings of others showing that patients with a low disease burden are more likely to benefit from a second transplantation. Late relapse led to a 10% decrement in LFS beyond the second year after second HCT. This differs from first HCT, in which most relapses occur within 2 years after HCT.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30194027

RESUMO

We report on 499 patients with severe aplastic anemia aged ≥ 50years who underwent hematopoietic cell transplantation (HCT) from HLA-matched sibling (n = 275, 55%) or HLA-matched (8/8) unrelated donors (n = 187, 37%) between 2005 and 2016. The median age at HCT was 57.8 years; 16% of patients were 65 to 77years old. Multivariable analysis confirmed higher mortality risks for patients with performance score less than 90% (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.03 to 1.92; P = .03) and after unrelated donor transplantation (HR, 1.47; 95% CI, 1 to 2.16; P = .05). The 3-year probabilities of survival for patients with performance scores of 90 to 100 and less than 90 after HLA-matched sibling transplant were 66% (range, 57% to 75%) and 57% (range, 47% to 76%), respectively. The corresponding probabilities after HLA-matched unrelated donor transplantation were 57% (range, 48% to 67%) and 48% (range, 36% to 59%). Age at transplantation was not associated with survival, but grades II to IV acute graft-versus-host disease (GVHD) risks were higher for patients aged 65years or older (subdistribution HR [sHR], 1.7; 95% confidence interval, 1.07 to 2.72; P = .026). Chronic GVHD was lower with the GVHD prophylaxis regimens calcineurin inhibitor (CNI) + methotrexate (sHR, .52; 95% CI, .33 to .81; P = .004) and CNI alone or with other agents (sHR, .27; 95% CI, .14 to .53; P < .001) compared with CNI + mycophenolate. Although donor availability is modifiable only to a limited extent, choice of GVHD prophylaxis and selection of patients with good performance scores are key for improved outcomes.

14.
Biol Blood Marrow Transplant ; 24(12): 2487-2492, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30142417

RESUMO

Graft-versus-host disease (GVHD) rates are higher after unrelated donor transplantation; thus, we examined whether there would be differences in transplant outcomes by graft type in children and adolescents with acute leukemia. The primary endpoint was overall survival. We studied 872 patients <18 years old who were transplanted with bone marrow (n = 650) or peripheral blood (n = 222) from unrelated donors. The characteristics of the 2 groups were comparable, except recipients of bone marrow were younger than recipients of peripheral blood (median age, 10 versus 12 years). Grades 2 to 4 (hazard ratio [HR], 1.48; P < .001) and grades 3 and 4 acute (HR, 1.69; P < .001) and chronic GVHD (HR, 1.92; P < .001) were higher with transplantation of peripheral blood than with bone marrow. Although relapse risks were lower after peripheral blood transplants (HR, 0.76; P = .05), transplant-related mortality (HR, 1.91; P = .003) and overall mortality (HR, 1.34; P = .032) were higher than with bone marrow transplants. The 8-year probability of overall survival after transplantation of bone marrow was 47% compared with 42% after peripheral blood. The 8-year probability of leukemia-free survival was 40% after transplantation of bone marrow and peripheral blood. Lower relapse after transplantation of peripheral blood negated the survival advantage after transplantation of bone marrow. The observed higher acute and chronic GVHD seen with peripheral blood suggest cautious use of this graft in children and adolescents with acute leukemia.

15.
Haematologica ; 103(8): 1251-1252, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30065017
16.
Blood Adv ; 2(16): 2095-2103, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30135184

RESUMO

In this study, we sought to identify specific individual high-intensity or reduced-intensity conditioning regimens with the best relapse-free survival (RFS) rather than the global high- vs reduced-intensity regimen comparison. Patients (median age, 58 years) with acute myeloid leukemia (AML; n = 1258), who were in first or subsequent remission, or with MDS (n = 951) who had refractory anemia with unilineage or multilineage dysplasia, 5q- syndrome, or refractory anemia with excess blasts received nonirradiation-containing regimens and were transplanted between 2009 and 2014 in the United States. Three-year RFS with high-intensity busulfan/cyclophosphamide (Bu4/Cy; 44%) was comparable to conditioning with high-intensity fludarabine/busulfan (Flu/Bu4; 44%), reduced-intensity fludarabine/melphalan (Flu/Mel; 52%; P = .53), and Flu/Mel + anti-thymocyte globulin (ATG; 44%; P = .38). RFS was lower with reduced-intensity Flu/Bu2 + ATG (31%; P = .0006). RFS was also lower with high-intensity Flu/Bu4 + ATG (38%; P = .05) and reduced-intensity Flu/Bu2 (38%; P = .02), although the difference did not reach the level of significance set for these analysis. RFS with Flu/Mel was superior to RFS with Flu/Bu2 (P = .01) and Flu/Bu2 + ATG (P = .0006). The 3-year incidence of relapse was 22% with Flu/Mel compared with 46% with Flu/Bu2 and 56% with Flu/Bu2 + ATG. With only a modest reduction in nonrelapse mortality with the Flu/Bu2 regimens, the higher relapse incidence resulted in lower RFS. The data support optimal RFS with Bu4/Cy, Flu/Bu4, and Flu/Mel regimens for AML in remission or MDS. The low relapse rate with reduced-intensity Flu/Mel resulted in RFS comparable to that after the higher-intensity regimens.

17.
Blood ; 132(13): 1438-1451, 2018 Sep 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).

18.
Blood ; 131(24): 2603-2604, 2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29903869
19.
Blood Adv ; 2(11): 1180-1186, 2018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-29794073

RESUMO

We sought to identify whether posttransplantation cyclophosphamide (PT-Cy) reduces or eliminates the detrimental impact of HLA mismatching on outcomes of HLA-haploidentical related donor transplantation for acute leukemia. Data from 2143 donor-recipient pairs (n = 218 haploidentical sibling; n = 218 offspring; n = 1707 HLA-matched sibling) with acute myeloid or lymphoblastic leukemia were studied. All received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis while high-dose PT-Cy was also given to recipients of haploidentical transplant. Patient age correlated with donor-recipient relationship: haploidentical siblings donated to patients aged 18 to 54 years whereas offspring donated to patients aged 55 to 76 years. Therefore, transplant outcomes were examined separately in the 2 patient age groups. In patients aged 18 to 54 years, there were no significant differences in outcomes except chronic GVHD, which was lower after haploidentical sibling compared to HLA-matched sibling transplant (hazard ratio [HR], 0.63; P < .001). In patients aged 55 to 76 years, despite lower chronic GVHD (HR, 0.42; P < .001), graft failure (14% vs 6%; P = .003), nonrelapse mortality (HR, 1.48; P = .02), and overall mortality (HR, 1.32; P = .003) were higher after transplant from offspring compared with an HLA-matched sibling. These data demonstrate a superior outcome in older recipients when using an HLA-matched sibling instead of offspring, although there were differences in transplant platforms (GVHD prophylaxis and graft type) between the 2 groups. Validation of these findings requires a prospective randomized trial wherein the transplant platforms can be closely matched.

20.
Blood Adv ; 2(3): 299-307, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29440002

RESUMO

We studied the association between non-HLA donor characteristics (age, sex, donor-recipient relationship, blood group [ABO] match, and cytomegalovirus [CMV] serostatus) and transplant outcomes after T-cell-replete HLA-haploidentical transplantation using posttransplantation cyclophosphamide (PT-Cy) in 928 adults with hematologic malignancy transplanted between 2008 and 2015. Siblings (n = 358) and offspring (n = 450) were the predominant donors, with only 120 patients having received grafts from parents. Although mortality risks were higher with donors aged 30 years or older (hazard ratio, 1.39; P < .0001), the introduction of patient age to the Cox regression model negated the effect of donor age. Two-year survival adjusted for CMV seropositivity, disease, and disease risk index was lower in patients aged 55 to 78 years after transplantation of grafts from donors younger than 30 years (53%) or aged at least 30 years (46%) compared with younger patients who received grafts from donors younger than 30 years (61%) and at least 30 years (60%; P < .0001). Similarly, 2-year survival in patients aged 55 to 78 years was lower after transplantation of grafts from siblings (45%) or offspring (48%) compared with patients aged 18 to 54 years after transplantation of grafts from siblings (62%), offspring (58%), and parents (61%; P < .0001). Graft failure was higher after transplantation of grafts from parents (14%) compared with siblings (6%) or offspring (7%; P = .02). Other non-HLA donor characteristics were not associated with survival or graft failure. The current analyses suggest patient and disease, rather than non-HLA donor characteristics, predominantly influence survival in adults.

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