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Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT
Battipaglia, G., Galimard, J. E., Labopin, M., Raiola, A. M., Blaise, D., Ruggeri, A., Koc, Y., Gülbas, Z., Vitek, A., Sica, S., et al
Bone marrow transplantation. 2022
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Editor's Choice
Abstract
Whether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24, p < 0.01; HR 2.65, 95% CI 1.46-4.81, p < 0.01, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14, p = 0.02; Haplo-PB: 1.47, 95% CI 1.05-2.05, p = 0.02); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21, p = 0.04; Haplo-PB: HR 1.51, 95% CI 1.05-2.19, p = 0.03). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81; p < 0.01), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD. Use of PTCy in 1Ag-MMUD-HCT is a valid alternative to consider when using alternative donors. Larger analysis of 1Ag-MMUD versus Haplo-HCT are warranted.
PICO Summary
Population
Adults with acute myeloid leukaemia, undergoing allo-HCT with post-transplant cyclophosphamide in first or second complete remission, identified from the EBMT database (n=1751)
Intervention
Haploidentical transplantation: Haplo using bone marrow (Haplo-BM, n = 647) or using peripheral blood (Haplo-PB, n = 949))
Comparison
One-antigen mismatched unrelated donor transplantation (1Ag-MMUD-PB, n = 155)
Outcome
Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.28, 95% CI 1.23-4.24; HR 2.65, 95% CI 1.46-4.81, respectively). Haplo groups experienced a lower leukemia-free survival (LFS) compared to 1Ag-MMUD-PB (Haplo-BM: HR 1.51, 95% CI 1.06-2.14; Haplo-PB: 1.47, 95% CI 1.05-2.05); overall survival (OS) was also lower in Haplo-HCT (Haplo-BM: HR 1.50, 95% CI 1.02-2.21; Haplo-PB: HR 1.51, 95% CI 1.05-2.19). No differences were observed for graft-versus-host/relapse-free survival (GRFS) and relapse incidence (RI). Haplo-BM was associated with a lower risk of grade III-IV acute graft-versus-host disease (GVHD) (HR 0.44, 95% CI 0.24-0.81), while no statistical differences were observed between groups for grade II-IV aGVHD and for cGVHD.
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[The impact of donor-to-recipient gender compatibility on outcomes of haploid hematopoietic stem cell transplantation in patients with hematological malignancies]
Hu, S. S., Wu, Y. B., Zhu, P. P., Shi, J. M., Yu, J., Zhao, Y. M., Lai, X. Y., Liu, L. Z., Fu, H. R., Huang, H., et al
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi. 2022;43(12):992-1002
Abstract
Objective: To investigate how gender differences between the donor and the recipient affect the effectiveness of antithymocyte globulin (ATG) and pure peripheral blood stem cell (PBSC) hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematological diseases. Methods: From February 2015 to September 2020, 648 hematological malignancies patients underwent myeloablative condition regimen haplo-HSCT treatment at the Bone Marrow Transplant Center of the First Affiliated Hospital of Zhejiang University. The median age was 32 (14-62) years, with 363 males (56.0% ) and 285 females (44.0% ) present. 242 cases of acute lymphoblastic leukemia (ALL) (37.3% ) , 293 cases of acute myeloid leukemia (AML) (45.2% ) , 56 cases of myelodysplastic syndrome (MDS) (8.7% ) , 27 cases of non-Hodgkin's lymphoma (NHL) (4.2% ) , and 30 cases of other hematological malignancies (4.6% ) . Results: ① The 3-year overall survival (OS) , DFS, the incidence of Ⅱ-Ⅳ grade acute graft-versus-host disease (aGVHD) , the incidence of Ⅲ-Ⅳ grade aGVHD, the 3-year incidence of moderate & severe chronic GVHD (cGVHD) , severe cGVHD, the 3-year incidence of relapse, and NRM of the whole group were (73.10±1.90) % , (70.80±1.90) % , (33.96±1.87) % , (13.08±1.33) % , (35.10±2.14) % , (10.66±1.38) % , (19.43±1.67) % , and (9.80±1.24) % , respectively. ②There was no statistically significant difference between the donor-recipient gender match and donor-recipient gender mismatch groups in the 28-day cumulative neutrophil engraftment rate, 28-day cumulative platelet engraftment rate, the incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, the cumulative incidence of relapse, NRM, and incidence of moderate & severe cGVHD, severe cGVHD. ③The 28-day cumulative neutrophil engraftment rate did not differ statistically between the male-female, female-female, male-male, and female-male groups (P=0.148) . The incidence of Ⅱ-Ⅳ grade aGVHD, the incidence of Ⅲ-Ⅳ grade aGVHD, 3-year OS, 3-year DFS, cumulative relapse rate, and NRM, and the incidence of cGVHD were not statistically different among the four groups (P>0.05) . The 28-day cumulative platelet engraftment rate of the female-male group was significantly lower than male-female group, and the female-female group [ (91.45±2.63) % vs. (94.77±1.75) % , P=0.004; (91.45±2.63) % vs. (95.54±2.05) % , P=0.005]. No significant difference existed in the 28-day cumulative platelet engraftment rate between the female-male group and the male-male group [ (91.45±2.63) % vs. (95.08±1.41) % , P=0.284]. ④Among patients ≤35 years old, the 3-year incidence of severe cGVHD patients receiving sister donors and sibling donors were (26.71±5.90) % and (10.33±4.43) % , respectively (P=0.054) . Patients accepting daughter donors and son donors had a 3-year incidence of moderate and severe cGVHD that was 40.07% vs. 27.41% , respectively, among those over 35 (40.07±6.65) % vs. (27.41±4.54) % (P=0.084) . ⑤Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate compared to the other groups [ (91.45±2.63) % vs. (95.08±0.95) % , P=0.037]. ⑥ Female donors to male recipients had a significantly lower 28-day cumulative platelet engraftment rate than the other groups in the ATG-Fresenius (ATG-F) 10 mg/kg group [ (89.29±4.29) % vs. (94.49±1.45) % , P=0.037]. But when compared to the other groups in the Rabbit Antihuman Thymocyte Immunoglobulin (rATG-T) 6 mg/kg group, the 28-day cumulative platelet implantation rate between female donors and male recipients was not significantly different [ (93.44±3.38) % vs. (95.62±1.26) % , P=0.404]. Conclusion: The main clinical outcomes of patients with malignant blood diseases following transplantation are unaffected by the gender combination of the donor and patient in the haplo-HSCT mode based on ATG and PBSC sources. Female donors to male recipients have a lower 28-day cumulative platelet engraftment rate and longer platelet engraftment times.
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HLA-Matching with PTCy: A Reanalysis of a CIBMTR Dataset with Propensity Score Matching and Donor Age
Ambinder, A. J., Jain, T., Tsai, H. L., Horowitz, M. M., Jones, R. J., Varadhan, R.
Blood advances. 2022
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Editor's Choice
Abstract
Blood or marrow transplantation (BMT) outcomes using haploidentical donors (Haplo) and post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GVHD) prophylaxis compare favorably to using HLA-matched donors with calcineurin inhibitor-based GVHD prophylaxis. A recent CIBMTR analysis of patients receiving homogenous PTCy-based prophylaxis found that, with reduced intensity conditioning, Haplo BMTs had worse outcomes than matched unrelated donor (MUD) BMTs. Due to significant differences in characteristics between the groups, we reanalyzed the dataset using propensity score matching and, additionally, added a donor age variable. MUD BMTs were matched to Haplo BMTs in a 1:5 ratio. After matching, no significant differences were found between groups across all measured baseline characteristics. Outcomes analyses demonstrated no significant differences in overall survival (HR of mortality with MUD vs Haplo [95% CI], 0.95[0.65-1.16], P=0.75), disease free survival (HR of relapse or death, 0.98[0.73-1.18], P=0.89), relapse rate (HR, 1.06[0.77-1.38], P=0.69), or non-relapse mortality (HR, 0.85[0.42-1.13], P=0.49) between the two groups. After stratification by conditioning intensity, MUD BMTs in the RIC cohort had a lower risk of NRM (HR, 0.56 [0.14-0.99], P=0.05), with no significant difference in other clinical outcomes. These results suggest that the effect of HLA matching on BMT outcomes with PTCy is less meaningful than previously reported and observed differences resulted in part from differences in donor age. Timely identification of a young, at least half-matched (related or unrelated) donor may be more important than finding a matched donor, if the latter leads to a substantial delay in BMT or use of an older donor.
PICO Summary
Population
Adults with acute myeloid leukaemia, acute lymphoblastic leukaemia in first or second complete remission, or myelodysplastic syndromes attending 111 bone marrow transplantation (BMT) centres across the USA and reported to the CIBMTR registry (n=837)
Intervention
BMT from haploidentical donors (Haplo, n=637, subset receiving reduced-intensity conditioning (RIC) n=341)
Comparison
BMT from matched unrelated donors (MUD, n=200, subset receiving RIC n=114)
Outcome
After matching, no significant differences were found between groups across all measured baseline characteristics. Outcomes analyses demonstrated no significant differences in overall survival (HR of mortality with MUD vs Haplo [95% CI], 0.95[0.65-1.16]), disease free survival (HR of relapse or death, 0.98[0.73-1.18]), relapse rate (HR, 1.06[0.77-1.38]), or non-relapse mortality (HR, 0.85[0.42-1.13]) between the two groups. After stratification by conditioning intensity, MUD BMTs in the RIC cohort had a lower risk of non-relapse mortality (HR, 0.56 [0.14-0.99]), with no significant difference in other clinical outcomes.
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A phase II study of post-transplant cyclophosphamide combined with tacrolimus for GVHD prophylaxis after HLA-matched related/unrelated allogeneic hematopoietic stem cell transplantation
Nakamae, H., Nakane, T., Okamura, H., Koh, H., Nakashima, Y., Hirose, A., Nakamae, M., Nishimoto, M., Kuno, M., Makuuchi, Y., et al
International journal of hematology. 2021
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Editor's Choice
Abstract
A combination of three post-transplant drugs, cyclophosphamide (PTCy), a calcineurin inhibitor, and mycophenolate mofetil, has long been used for prophylaxis of graft-versus-host-disease (GVHD) after HLA-haploidentical allogeneic hematopoietic cell transplantation (allo-HCT). Recently, this combination has been used following HLA-matched allo-HCT as well, but the optimal combination of drugs for GVHD prophylaxis in an HLA-matched setting remains unclear. This prospective phase II study evaluated the safety and efficacy of PTCy plus tacrolimus (TAC) for GVHD prophylaxis after allo-HCT from HLA-matched related donors (MRD) or HLA-matched unrelated donors (MUD). The cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days post-transplantation were 18% and 5.9%, respectively, in the MRD group, and 18% and 9.1%, respectively, in the MUD group. The cumulative incidences of moderate to severe chronic GVHD at 1 year were 12% and 9.1% in the MRD and MUD groups, respectively. The 1-year overall survival rates in the MRD and MUD groups were 88% and 64%, respectively, and the 1-year GVHD-free, relapse free survival rates were 59% and 50%, respectively. These results suggest that GVHD prophylaxis with a less intensive double drug combination (PT/Cy and TAC) might be feasible after HLA-matched allo-HCT.Clinical Trial Notation This trial was a prospective single-center trial registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; identification number: UMIN000023890) and the Japan Registry of Clinical Trials (jRCTs051180143).
PICO Summary
Population
Patients undergoing allogeneic transplant at a single centre in Japan, with post-Transplant cyclophosphamide (PTCy) plus tacrolimus (TAC) for GVHD prophylaxis (n=39)
Intervention
Matched related donor (MRD) transplantation (n=17)
Comparison
Matched unrelated donor (MUD) transplantation (n=22)
Outcome
The cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days post-transplantation were 18% and 5.9%, respectively, in the MRD group, and 18% and 9.1%, respectively, in the MUD group. The cumulative incidences of moderate to severe chronic GVHD at 1 year were 12% and 9.1% in the MRD and MUD groups, respectively. The 1-year overall survival rates in the MRD and MUD groups were 88% and 64%, respectively, and the 1-year GVHD-free, relapse free survival rates were 59% and 50%, respectively.
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HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis
Gooptu, M., Romee, R., St Martin, A., Arora, M., Al Malki, M., Antin, J. H., Bredeson, C. N., Brunstein, C. G., Chhabra, S., Fuchs, E. J., et al
Blood. 2021;138(3):273-282
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Editor's Choice
Abstract
Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced-intensity regimens were analyzed separately. Among recipients of reduced-intensity regimens, 2-year graft failure (3% vs 11%), acute grades 2 to 4 GVHD (hazards ratio [HR], 0.70; P = .022), acute grades 3 and 4 GVHD (HR, 0.41; P = .016), and nonrelapse mortality (HR, 0.43; P = .0008) were lower after MUD than with Haplo donor transplantation. Consequently, disease-free (HR, 0.74; P = .008; 55% vs 41%) and overall (HR, 0.65; P = .001; 67% vs 54%) survival were higher with MUD than with Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% vs 88%) was higher and grades 3 and 4 acute (HR, 0.39; P = .07) and chronic GVHD (HR, 0.66; P = .05) were lower after MUD than with Haplo donor transplantation. There were no differences in graft failure, relapse, nonrelapse mortality, and disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced-intensity conditioning regimens.
PICO Summary
Population
Patients reported to the CIBMTR registry, undergoing transplantation for acute leukaemia or myelodysplastic syndrome (n=2320)
Intervention
Haploidentical transplantation with post-transplant cyclophosphamide (PTCy) (Haplo, n=2036)
Comparison
Matched unrelated donor transplantation with PTCy prophylaxis (MUD, n=284)
Outcome
Recipients of myeloablative and reduced-intensity regimens were analysed separately. Among recipients of reduced-intensity regimens, 2-year graft failure (3% vs 11%), acute grades 2 to 4 GVHD (hazard ratio [HR], 0.70), acute grades 3 and 4 GVHD (HR, 0.41), and nonrelapse mortality (HR, 0.43) were lower after MUD than with Haplo donor transplantation. Consequently, disease-free (HR, 0.74; 55% vs 41%) and overall (HR, 0.65; 67% vs 54%) survival were higher with MUD than with Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% vs 88%) was higher and grades 3 and 4 acute (HR, 0.39) and chronic GVHD (HR, 0.66) were lower after MUD than with Haplo donor transplantation. There were no differences in graft failure, relapse, nonrelapse mortality, and disease-free and overall survival between donor types with myeloablative conditioning regimens.
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Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching
Irene, G. C., Albert, E., Anna, B. V., Rahinatu, A., Silvana, N., Silvana, S., Ana, G., Jordi, L., Carolina, C. A., Miquel, G., et al
Bone marrow transplantation. 2020;:1-10
Abstract
Post-transplant cyclophosphamide (PTCy) has become a promising option after allo-SCT, but infections may be more common than in traditional protocols. We herein report 117 consecutive adults who received PTCy-based alloSCT in our hospital: HaploSCT (34%), MRD (19%), and VUD (47%), respectively. The 18-month incidence of severe bacterial, viral, and IFI was 56%, 69%, and 8.7%, without differences between donor type, except for CMV infection and viral hemorrhagic cystitis, which had a higher incidence in the haploSCT cohort (58% vs. 43% and 30% vs. 8% on day +90, p < 0.05). Late infections by conventional respiratory viruses were common in all groups [33/87 (38%)]. The 2-year survival was 72% and did not differ by donor type. IRM at day 30, day 100, and 18 months was 1.7%, 4.4%, and 12%, without differences by donor type (p = 0.7). The primary cause of IRM was bacterial infection (42%). Grade 2-4 acute GvHD was the only independent predictor of IRM. Donor type had no impact on IRM or on survival. In our study, severe infections were common in all donor types using PTCy, with higher rates of early post-engraftment CMV-I and viral HC in haploSCT recipients, although lethal infections were uncommon and similar in all donor types.
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Single-Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide is a Suitable Alternative for Patients Lacking HLA-Matched Donors
Jorge, A. S., Suarez-Lledo, M., Pereira, A., Gutierrez, G., Fernandez-Aviles, F., Rosinol, L., Llobet, N., Solano, T., Urbano-Ispizua, A., Rovira, M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
The optimal prophylaxis regimen for graft-versus-host disease (GVHD) in the setting of mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation (alloSCT) is not defined. The use of high-dose post-transplant cyclophosphamide (PTCy) in haploidentical transplantation has proven feasible and effective in overcoming the negative impact of HLA-disparity on survival. We hypothesized that PTCy could also be effective in the setting of MMUD transplantation. We retrospectively analyzed 86 consecutive adult recipients of alloHSCT in our institution, comparing two contemporaneous groups: PTCyMMUD (n=26) vs. matched unrelated donor (MUD) (n=60). Graft source was primarily peripheral blood (92%). All PTCyMMUD were HLA 7/8 (differences in HLA-class I loci in 92% of patients), and received PTCy plus tacrolimus + mofetil mycophenolate as GVHD prophylaxis. No differences were observed between PTCyMMUD and MUD in the 100-day cumulative incidence of acute GVHD grades II-IV (31% vs. 22%, respectively, P=0.59) and III-IV (8% vs. 10%, P=0.67). There was a trend for a lower incidence of moderate/severe chronic GVHD at 1-year after PTCyMMUD in comparison with MUD (22% vs. 41%, P=0.098). No differences between PTCyMMUD and MUD were found regarding non-relapse mortality (25% vs. 18%; P=0.52) or relapse rate (11% vs. 19%, P=0.18). Progression-free survival and overall survival at 2-year were similar in both cohorts (67% vs. 54%, HR 0.84, 95% CI 0.38-1.88; P= 0.68; and 72% vs. 57%, HR 0.71; 95% CI 0.31-1.67; P=0.44, respectively). The 2-year cumulative incidence of survival free of moderate-severe chronic GVHD and relapse tended to be higher in the PTCyMMUD group (47% vs. 24%; HR 0.60, 95% CI 0.31-1.14, P=0.12). We conclude that HLA 7/8 MMUD transplantation using PTCy plus tacrolimus is a suitable alternative for those patients who lack a MUD.
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Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch?
Robinson, T. M., Fuchs, E. J., Zhang, M. J., St Martin, A., Labopin, M., Keesler, D. A., Blaise, D., Bashey, A., Bourhis, J. H., Ciceri, F., et al
Blood advances. 2018;2(11):1180-1186
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Abstract
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.
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Effect of donor characteristics on haploidentical transplantation with posttransplantation cyclophosphamide
McCurdy, S. R., Zhang, M. J., St Martin, A., Al Malki, M. M., Bashey, A., Gaballa, S., Keesler, D. A., Hamadani, M., Norkin, M., Perales, M. A., et al
Blood advances. 2018;2(3):299-307
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Abstract
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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10.
Similar outcomes after haploidentical transplantation with post-transplant cyclophosphamide versus HLA-matched transplantation: a meta-analysis of case-control studies
Gu, Z., Wang, L., Yuan, L., Huang, W., Li, M., Guan, L., Wang, Q., Gao, Z., Zhao, S., Luo, L., et al
Oncotarget. 2017;8(38):63574-63586
Abstract
BACKGROUND Outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PT-Cy) have greatly improved. It remains unknown whether haplo-HCT with PT-Cy was associated with poor outcomes when compared with HLA-matched HCT. To address this issue, we performed a meta-analysis to compare outcomes of haplo-HCT with PT-Cy with those of HLA-matched HCT. METHODS A systematic search for case-control studies were performed in PubMed, Embase and Cochrane Library databases. Using a random model, the risk ratios (RRs) and 95% confidence intervals (95% CI) were pooled for the final analysis. RESULTS Nine case-control studies including 2258 patients (827 patients in the haplo-HCT with PT-Cy group, 748 controls from HLA-matched related donors (MRD), and 683 controls from HLA-matched unrelated donors (MUD)) met the inclusion criteria. No differences were found between haplo-HCT with PT-Cy and HLA-matched HCT with regard to acute graft-versus-host-disease (GVHD), non-relapse mortality, relapse, progression free survival and overall survival. However, haplo-HCT with PT-Cy was found to be associated with a lower incidence of moderate to severe chronic GVHD (Haplo vs MRD: RR=0.54; 95% CI=0.39-0.75; Haplo vs MUD: RR=0.70; 95% CI=0.56-0.88). CONCLUSIONS The results of this meta-analysis suggest that haplo-HCT with PT-Cy can achieve comparable outcomes with those of HLA-matched HCT. Haploidentical donors can be a feasible and valid alternative when conventional HLA-matched donors are unavailable.