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Allogeneic Blood or Marrow Transplantation with Post-transplantation Cyclophosphamide for Peripheral T-cell Lymphoma: The Importance of Graft Source
Sterling, C. H., Hughes, M. S., Tsai, H. L., Yarkony, K., Fuchs, E. J., Swinnen, L. J., Paul, S., Bolaños-Meade, J., Luznik, L., Imus, P. H., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND The use of post-transplantation cyclophosphamide (PTCy) for graft-versus host-disease (GVHD) prophylaxis has revolutionized allogeneic blood or marrow transplantation (alloBMT), but there is limited published experience in peripheral T-cell lymphoma (PTCL). OBJECTIVES We sought to assess outcomes in patients with PTCL who underwent alloBMT with PTCy. STUDY DESIGN We reviewed the charts of all adult patients aged 18 years or older who underwent alloBMT with non-myeloablative conditioning and PTCy-based GVHD prophylaxis at the Sidney Kimmel Comprehensive Cancer Center between January 2004 and December 2020. RESULTS Sixty-five patients were identified. The median age was 59 years (range, 24-75 years). Lymphoma histology included PTCL-not otherwise specified (n=24), ALK-negative anaplastic large cell lymphoma (n=14), angioimmunoblastic T-cell lymphoma (n=7), enteropathy-associated T-cell lymphoma (n=6), hepatosplenic T-cell lymphoma (n=4), and other (n=10). Eleven patients were in first complete remission (CR1, 17%). The remaining patients were in first partial remission (PR1) or underwent salvage therapy to at least PR prior to transplant. Forty-eight patients received an alloBMT from a haploidentical related donor (74%), 10 from a fully matched donor (15%), and 7 from a mismatched unrelated donor (mMUD, 11%). All patients received fludarabine, cyclophosphamide, and total body irradiation (TBI). The graft source was bone marrow (BM) in 46 patients (71%) and peripheral blood (PB) in 19 patients (29%); all patients in the BM cohort received 200 cGy TBI, and most in the PB cohort (15/19) received 400 cGy TBI. GVHD prophylaxis was PTCy, mycophenolate mofetil, and a calcineurin inhibitor or sirolimus. With a median follow up of 2.8 years (range, 290 days-14.2 years), the 2-year PFS for the entire cohort was 49% (95% confidence interval [CI] 38-64%), and the 2-year OS was 55% (95% CI 44-69%). Outcomes were significantly improved in those receiving PB compared to BM, including 2-year PFS of 79% (95% CI 63-100%) vs. 39% (95% CI 27-56%), 2-year OS of 84% (95% CI 69-100%) vs. 46% (95% CI 33-63%), and 1-year cumulative incidence of (CuI) relapse of 5% (95% CI 0-16%) vs. 33% (95% CI 19-46%), with no difference in GVHD or non-relapse mortality (NRM). CONCLUSIONS AlloBMT with PTCy is safe and well-tolerated in patients with PTCL. Our data suggest increasing TBI dose to 400 cGy and using PB allografts may offer improved disease control and better survival outcomes, though additional studies are needed to confirm these findings.
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Impact of Center Experience with Donor Type on Outcomes: A Secondary Analysis BMT CTN 1101Open for Accrual June 2012Open for Accrual June 2012
Brunstein, C. G., O'Donnell, P. V., Logan, B., Dawson, P., Costa, L., Cutler, C., Craig, M., Hogan, W., M. Horowitz M, Horwitz, M. E., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND We reported on the results of Blood and Marrow Transplant (BMT) Clinical Trials Network (CTN) 1101, a randomized comparison between double umbilical cord blood (dUCB) and haploidentical (haplo) bone marrow (BM) with post-transplant cyclophosphamide (PTCy) in the nonmyeloablative setting that showed similar progression free survival (PFS) between the two treatment groups, but lower non-relapse mortality (NRM) and better of survival (OS) in the haplo arm. In this secondary analysis, we sought to investigate whether transplant center experience with haplo BM and/or dUCB hematopoietic cell transplant (HCT) had an impact on outcomes. PATIENTS AND METHODS All patients randomized in BMT CTN 1101 were included. Center experience was assigned based on the number transplants with each platform in the year prior to initiation of the study according to the Center for International Blood and Marrow Transplant Research (CIBMTR). Centers were then grouped as a dUCB-center (>10 dUCB, n=117, 10 centers), a haplo center (>10 haplo and ≤10 dUCB, n=110, 2 centers), or other-center (≤10 haplo and ≤10 dUCB HCTs, n=140, 21 centers). RESULTS After adjusting for age, Karnofsky performance score, and disease risk index, we found that haplo centers had lower overall mortality with this donor type, as compared to dUCB (HR 2.56, 95%CI, 1.44-4.56). In contrast, there were no differences in overall mortality between haplo and dUCB in centers that were experienced with dUCB (HR 1.02, 95%CI 0.59-1.79) or had limited-to-no experience with either dUCB or haplo (HR 1.36, 95%CI, 0.83-2.21). The higher risk of treatment failure and overall mortality in dUCB in haplo-experienced centers was driven by a significantly higher risk of relapse (HR 1.78, 95%CI, 1.07-2.97). CONCLUSION With the exception of worse outcomes among dUCB recipients in haplo-BM centers, the transplant center experience on the year prior to the initiation of BMT CTN 1101 had limited impact on the outcomes of this randomized clinical trial.
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Allogeneic Blood or Marrow Transplantation with High-Dose Post-transplantation Cyclophosphamide for Acute Lymphoblastic Leukemia in Patients Aged ≥55
Webster, J. A., Reed, M., Tsai, H. L., Ambinder, A., Jain, T., Dezern, A. E., Levis, M. J., Showel, M. M., Prince, G. T., Hourigan, C. S., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Patients ≥55 years-old with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy with 5-year overall survival of ∼20%. Tyrosine kinase inhibitors and novel B-cell targeted therapies improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (AlloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplants with low rates of non-relapse mortality (NRM) and graft-versus-host disease (GVHD). METHODS The transplant database at Johns Hopkins was queried for patients ≥ 55 years old who received alloBMT for ALL using PTCy. FINDINGS The database included 77 such patients. Most received reduced-intensity conditioning (RIC) (88.3%), were in first remission (CR1) (85.7%), and had B-lineage disease (90.9%). For the entire cohort, 5-year relapse-free survival (RFS) and overall survival (OS) were 46% (95% CI 34-57) and 49% (95% CI 37-60). Grade 3-4 acute GVHD occurred in only 3% of patients and chronic GVHD in 13%. In multivariable analysis, myeloablative conditioning led to worse RFS (HR 4.65, p=0.001); while transplant in CR1 (HR 0.30, p=0.004), and transplant for Ph+ ALL vs. T ALL (HR 0.29, p=0.03) improved RFS. Of the 54 patients who received RIC alloBMT in CR1 for B ALL, 5-year RFS and OS were 62% (95% CI 47-74) and 65% (95% CI 51-77), respectively, with a 5-year relapse incidence of 16% (95% CI 7-27) and NRM of 24% (95% CI 13-36). INTERPRETATION RIC AlloBMT with PTCy in CR1 represents a promising consolidation strategy for B ALL patients ≥ 55 years old. FUNDING NIH grants P01 CA225618 and P30 CA06973.
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"Allogeneic blood or marrow transplant with non-myeloablative conditioning and high dose cyclophosphamide-based graft-versus-host disease prophylaxis for secondary central nervous system lymphoma"
Sterling, C. H., Tsai, H. L., Holdhoff, M., Bolaños-Meade, J., Luznik, L., Fuchs, E. J., Huff, C. A., Gocke, C. B., Ali, S. A., Borrello, I. M., et al
Transplantation and cellular therapy. 2021
Abstract
Secondary central nervous system (CNS) lymphoma is a rare and often fatal complication of non-Hodgkin lymphoma (NHL). Treatment options include radiation therapy, high-dose systemic chemotherapy, intrathecal chemotherapy, and high-dose chemotherapy with autologous stem cell rescue, but outcomes remain poor. Allogeneic blood or marrow transplant (alloBMT) is widely used in relapsed/refractory systemic NHL. We sought to understand whether a graft-versus-lymphoma effect could maintain remission in CNS disease. Here we review outcomes in 20 consecutive patients with secondary CNS lymphoma who underwent alloBMT with non-myeloablative conditioning using fludarabine, cyclophosphamide, and 200cGy total-body irradiation. For graft-versus-host disease (GVHD) prophylaxis, all patients received post-transplant cyclophosphamide (PTCy), mycophenolate mofetil, and a calcineurin inhibitor. With a median follow up of 4.1 years, the median overall survival for the entire cohort was not reached. Median progression-free survival was 3.8 years (95% confidence interval [CI] 5.3 months - not reached). The cumulative incidence of relapse was 25% (95% CI 5-45%), and non-relapse mortality was 30% (95% CI 5-54%) at 4 years. Of the 5 patients who relapsed, 2 were CNS only, 1 was systemic only, and 2 were combined CNS / systemic. The use of alloBMT in CNS lymphoma deserves further investigation.
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Umbilical cord blood or HLA-haploidentical transplantation: Real world outcomes vs randomized trial outcomes
O'Donnell, P. V., Brunstein, C. G., Fuchs, E. J., Zhang, M. J., Allbee-Johnson, M., Antin, J. H., Leifer, E. S., Elmariah, H., Grunwald, M. R., Hashmi, H., et al
Transplantation and cellular therapy. 2021
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Editor's Choice
Abstract
BACKGROUND Randomized clinical trials offer the highest quality data for modifying clinical practice. Results of a phase III randomized trial of non-myeloablative transplantation for adults with high- risk hematologic malignancies with two umbilical cord blood (UCB) units (n=183) or HLA-haploidentical relative bone marrow (Haplo-BM) (n=154) revealed 2-year progression-free survival (PFS) of 41% and 35% after Haplo-BM and two-unit UCB transplantation, respectively (p=0.41); overall survival was 57% and 46%, respectively (p=0.04), BMT CTN 1101; NCT01597778. OBJECTIVES We sought to examine the generalizability of BMT CTN 1101 to a contemporaneous cohort beyond the trial's pre-specified 2-year outcomes. All transplantation occurred between June 2012 and June 2018 in the United States. We hypothesized that the results of a rigorous phase III randomized trial will be generalizable. Changes in graft selection for HLA-haploidentical relative transplantation during the trial period allowed comparison of outcomes after transplantation with Haplo-BM to those after haploidentical peripheral blood (Haplo-PB). STUDY DESIGN The trial's broad eligibility criteria were applied to the data source of the Center for International Blood and Marrow Transplant Research to select non-trial subjects. Extended follow up of trial subjects was obtained from this data source. Three separate analyses were performed: 1) trial subjects beyond the trial's 2-year endpoint 2) comparison of trial subjects to a contemporaneous cohort of non-trial subjects (195 two-unit UCB, 358 Haplo-BM, 403 Haplo-PB) and 3) comparison of non-trial subjects by donor and graft type. Multivariate analyses were performed using Cox proportional hazards models for comparison of outcomes by treatment groups. RESULTS With longer follow up of the trial cohorts, 5-year PFS (37% versus 29%, p=0.08) and overall survival (42% versus 36%, p=0.06) were not significantly different between treatment groups. We then compared the trial results to comparable real-world transplantations. Five-year overall survival after trial and non-trial two-unit UCB (36% versus 41%, p=0.48) and trial and non-trial Haplo-BM (42% versus 47%, p=0.80) transplantation were not different confirming generalizability. The randomized trial did not accrue as planned and therefore lacked the statistical power to detect a 15% difference in progression-free survival. With substantially larger numbers of non-trial Haplo-BM transplantations, 5-year survival was higher after non-trial Haplo-BM compared to trial two-unit UCB (47% versus 36%, p=0.012). Non-trial patients who received Haplo-PB transplantation had higher 5-year survival (54%) compared to trial (HR 0.76, p=0.044) and non-trial (HR 0.78, p=0.026) Haplo-BM. Similarly, survival was higher after Haplo-PB compared to trial (HR 0.57, p<0.0001) and non-trial UCB (HR 0.63, p=0.0002). CONCLUSION When considering alternative donor low intensity conditioning regimen transplantation, a haploidentical relative is preferred. Further, PB is the preferred graft.
PICO Summary
Population
Patients enrolled on the BMT CTN 1101 trial (n=337), and non-trial patients identified from the CIBMTR database (n=956), who met the criteria for BMT CTN 11001 but were not enrolled (total n=1293)
Intervention
two umbilical cord blood (UCB) units (trial: n=183, non-trial: n=195; total n=378)
Comparison
HLA-haploidentical relative bone marrow (Haplo-BM, trial: n=154, non-trial: n=358; total n=512); Non-trial cohort undergoing peripheral blood haploidentical transplant (Haplo-PB, n=403)
Outcome
With longer follow up of the trial cohorts, 5-year PFS (37% versus 29%, p=0.08) and overall survival (42% versus 36%) were not significantly different between treatment groups. We then compared the trial results to comparable real-world transplantations. Five-year overall survival after trial and non-trial two-unit UCB (36% versus 41%) and trial and non-trial Haplo-BM (42% versus 47%) transplantation were not different confirming generalizability. The randomized trial did not accrue as planned and therefore lacked the statistical power to detect a 15% difference in progression-free survival. With substantially larger numbers of non-trial Haplo-BM transplantations, 5-year survival was higher after non-trial Haplo-BM compared to trial two-unit UCB (47% versus 36%). Non-trial patients who received Haplo-PB transplantation had higher 5-year survival (54%) compared to trial (HR 0.76) and non-trial (HR 0.78) Haplo-BM. Similarly, survival was higher after Haplo-PB compared to trial (HR 0.57) and non-trial UCB (HR 0.63).
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HLA Informs Risk Predictions after Haploidentical Stem Cell Transplantation with Post-transplantation Cyclophosphamide
Fuchs, E. J., McCurdy, S. R., Solomon, S. R., Wang, T., Herr, M. M., Modi, D., Grunwald, M. R., Nishihori, T., Kuxhausen, M., Fingerson, S., et al
Blood. 2021
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Editor's Choice
Abstract
Hematopoietic cell transplantation from HLA-haploidentical related donors is increasingly used to treat hematologic cancers; however, characteristics of the optimal haploidentical donor have not been established. We studied the role of donor HLA mismatching in graft-versus-host disease (GVHD), disease recurrence and survival after haploidentical donor transplantation with post-transplantation cyclophosphamide (PTCy) for 1434 acute leukemia or myelodysplastic syndrome patients reported to the Center for International Blood and Marrow Transplant Research. The impact of mismatching in the graft-versus-host vector for HLA-A, -B, -C, -DRB1, and -DQB1 alleles, the HLA-B leader, and HLA-DPB1 T-cell epitope (TCE) were studied using multivariable regression methods. Outcome was associated with HLA (mis)matches at individual loci rather than the total number of HLA mismatches. HLA-DRB1 mismatches were associated with lower risk of disease recurrence. HLA-DRB1-mismatching with HLA-DQB1-matching correlated with improved disease-free survival. HLA-B leader matching and HLA-DPB1 TCE-non-permissive mismatching were each associated with improved overall survival. HLA-C matching lowered chronic GVHD risk, and the level of HLA-C expression correlated with transplant-related mortality. Matching status at the HLA-B leader and HLA-DRB1, -DQB1 and -DPB1 predicted disease-free survival, as did patient and donor CMV serostatus, patient age and co-morbidity index. A web-based tool was developed to facilitate selection of the best haploidentical related donor by calculating disease-free survival based on these characteristics. In conclusion, HLA factors influence the success of haploidentical transplantation with PTCy. HLA-DRB1 and -DPB1 mismatching and HLA-C, -B leader, and -DQB1 matching are favorable. Consideration of HLA factors may help to optimize the selection of haploidentical related donors.
PICO Summary
Population
Patients undergoing transplant for acute leukaemia or myelodysplastic syndrome at centres reporting to the CIBMTR (n=1434)
Intervention
The impact of mismatching in the graft-versus-host vector for HLA-A, -B, -C, -DRB1, and -DQB1 alleles, the HLA-B leader, and HLA-DPB1 T-cell epitope (TCE) were studied using multivariable regression methods.
Comparison
None
Outcome
Outcome was associated with HLA (mis)matches at individual loci rather than the total number of HLA mismatches. HLA-DRB1 mismatches were associated with lower risk of disease recurrence. HLA-DRB1-mismatching with HLA-DQB1-matching correlated with improved disease-free survival. HLA-B leader matching and HLA-DPB1 TCE-non-permissive mismatching were each associated with improved overall survival. HLA-C matching lowered chronic GVHD risk, and the level of HLA-C expression correlated with transplant-related mortality. Matching status at the HLA-B leader and HLA-DRB1, -DQB1 and -DPB1 predicted disease-free survival, as did patient and donor CMV serostatus, patient age and co-morbidity index. A web-based tool was developed to facilitate selection of the best haploidentical related donor by calculating disease-free survival based on these characteristics.
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Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial
Fuchs, E. J., O'Donnell, P. V., Eapen, M., Logan, B., Antin, J. H., Dawson, P., Devine, S., Horowitz, M. M., Horwitz, M. E., Karanes, C., et al
Blood. 2021;137(3):420-428
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Editor's Choice
Abstract
Results of 2 parallel phase 2 trials of transplantation of unrelated umbilical cord blood (UCB) or bone marrow (BM) from HLA-haploidentical relatives provided equipoise for direct comparison of these donor sources. Between June 2012 and June 2018, 368 patients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were randomly assigned to undergo UCB (n = 186) or haploidentical (n = 182) transplant. Reduced-intensity conditioning comprised total-body irradiation with cyclophosphamide and fludarabine for both donor types. Graft-versus-host disease prophylaxis for UCB transplantation was cyclosporine and mycophenolate mofetil (MMF) and for haploidentical transplantation, posttransplant cyclophosphamide, tacrolimus, and MMF. The primary end point was 2-year progression-free survival (PFS). Treatment groups had similar age, sex, self-reported ethnic origin, performance status, disease, and disease status at randomization. Two-year PFS was 35% (95% confidence interval [CI], 28% to 42%) compared with 41% (95% CI, 34% to 48%) after UCB and haploidentical transplants, respectively (P = .41). Prespecified analysis of secondary end points recorded higher 2-year nonrelapse mortality after UCB, 18% (95% CI, 13% to 24%), compared with haploidentical transplantation, 11% (95% CI, 6% to 16%), P = .04. This led to lower 2-year overall survival (OS) after UCB compared with haploidentical transplantation, 46% (95% CI, 38-53) and 57% (95% CI 49% to 64%), respectively (P = .04). The trial did not demonstrate a statistically significant difference in the primary end point, 2-year PFS, between the donor sources. Although both donor sources extend access to reduced-intensity transplantation, analyses of secondary end points, including OS, favor haploidentical BM donors. This trial was registered at www.clinicaltrials.gov as #NCT01597778.
PICO Summary
Population
Patients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukaemia in remission (n=368)
Intervention
Cord blood transplantation (UCB, n=186)
Comparison
Haploidentical transplantation (n=182)
Outcome
Two-year PFS was 35% after UCB compared with 41% haploidentical transplant. Prespecified analysis of secondary end points recorded higher 2-year nonrelapse mortality after UCB: 18%, compared with 11% for haploidentical transplantation. This led to lower 2-year overall survival (OS) after UCB compared with haploidentical transplantation, 46% and 57%, respectively. The trial did not demonstrate a statistically significant difference in the primary end point, 2-year PFS, between the donor sources.
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Post-Transplant Cyclophosphamide (PTCy) is Associated with Increased Cytomegalovirus Infection: A CIBMTR Analysis
Goldsmith, S. R., Abid, M. B., Auletta, J. J., Bashey, A., Beitinjaneh, A., Castillo, P., Chemaly, R. F., Chen, M., Ciurea, S. O., Dandoy, C. E., et al
Blood. 2021
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Editor's Choice
Abstract
Prior studies suggest increased CMV infection following haploidentical donor transplantation with post-transplant cyclophosphamide (HaploCy). The role of allograft source and PTCy in CMV infection and disease is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection as well as transplant outcomes as it relates to CMV serostatus and occurrence of CMV infection by d180. We examined patients reported to CIBMTR between 2012-2017 who had received HaploCy (n = 757), Sib with PTCy (SibCy, n=403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n=1605) for AML/ALL/MDS. Cumulative incidences of CMV infection by d180 were 42% (99% CI, 37-46), 37% (31 - 43), and 23% (20 - 26), respectively [p<0.001]. CMV end-organ disease was statistically comparable. CMV infection risk was highest for CMV-Seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor [HaploCy (n=545): HR 50.3 (14.4 - 175.2); SibCy (n=279): HR 47.7 (13.3 - 171.4); SibCNI (n=1065): HR 24.4 (7.2 - 83.1); p<0.001]. D+/R- patients also had increased risk for CMV infection. Among seropositive recipients or those developing CMV infection, HaploCy had worse OS and NRM. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic GVHD overall, but CMV infection in PTCy recipients was associated with higher cGVHD (p=0.006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally CMV infection may negate the cGVHD protection of PTCy. This study supports aggressive prevention strategies in all patients receiving PTCy.
PICO Summary
Population
Patients with acute myeloid leukaemia, acute lymphoblastic leukaemia or myelodysplastic synrome (n=2765)
Intervention
Haploidentical transplantation with post-transplant cyclophosphamide (HaploCy, n=757),
Comparison
Sibling donor with post-transplant cyclophosphamide (SibCy, n=403), or Sibling donor with calcineurin inhibitor-based prophylaxis (SibCNI, n=1605)
Outcome
Cumulative incidences of CMV infection by day 180 were 42% (HaploCy), 37% (SibCy), and 23% (SibCNI), respectively. CMV end-organ disease was statistically comparable. CMV infection risk was highest for CMV-Seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor [HaploCy (n=545): HR 50.3; SibCy (n=279): HR 47.7; SibCNI (n=1065): HR 24.4. D+/R- patients also had increased risk for CMV infection. Among seropositive recipients or those developing CMV infection, HaploCy had worse OS and NRM. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic GVHD overall, but CMV infection in PTCy recipients was associated with higher cGVHD. PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally CMV infection may negate the cGVHD protection of PTCy.
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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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10.
Engraftment of Double Cord Blood Transplantation after Nonmyeloablative Conditioning with Escalated Total Body Irradiation Dosing to Facilitate Engraftment in Immunocompetent Patients
Brunstein, C. G., DeFor, T. E., Fuchs, E. J., Karanes, C., McGuirk, J. P., Rezvani, A. R., Eapen, M., O'Donnell, P. V., Weisdorf, D. J.
Transplantation and cellular therapy. 2021;27(10):879.e1-879.e3
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Editor's Choice
Abstract
To improve accrual to a randomized clinical trial of double unrelated cord blood (dUCB) versus HLA-haploidentical bone marrow (haplo-BM) transplantation, patients with less previous therapy and potentially greater immunocompetence were enrolled. To reduce the risk of graft rejection, patients randomized to receive dUCB received a higher dose of total body irradiation (TBI) (300 cGy versus 200 cGy). In this study, we investigated whether the inclusion of recipients of 300 cGy TBI influenced the trial outcomes. This was a secondary analysis of dUCB recipients, 161 who received TBI 200 cGy and 18 who received TBI 300 cGy. Fine and Gray regression was used to evaluate the effect of TBI dose on relapse and nonrelapse mortality (NRM). Cox regression was used for evaluation of neutrophil engraftment and overall survival. Patient characteristics were similar in the 2 TBI dose subgroups. The probability of neutrophil engraftment was 100% for patients who received TBI 300 cGy versus 91% (95% confidence interval, 86% to 95%) for those who received TBI 200 cGy (P = .64), which was similar after regression analysis adjusting for age, total infused nucleated cell dose, HLA matching to the patient, and comorbidity score. We also investigated whether the lower survival probability and higher cumulative incidence of NRM observed in the dUCB arm of BMT CTN 1101 could be influenced by the TBI 300 cGy patient subset. There was no significant difference in the 1-year incidences of NRM and relapse or in 1-year survival, even after adjustment in multivariate analysis. Patients in BMT CTN 1101 who received TBI 300 cGy and 200 cGy had similar engraftment and early mortality. We conclude that inclusion of a modified regimen for dUCB transplantation had no demonstrable influence on this large randomized trial.
PICO Summary
Population
Adults aged up to 70 years with acute leukaemia or lymphoma, enrolled in BMT CTN 1101 trial, and who received a double cord blood (dUCB) graft (n=179)
Intervention
Total body irradiation (TBI) conditioning 200 cGy (n=161)
Comparison
Total body irradiation (TBI) conditioning 300 cGy (n=18)
Outcome
The probability of neutrophil engraftment was 100% for patients who received TBI 300 cGy versus 91% (95% confidence interval, 86% to 95%) for those who received TBI 200 cGy, which was similar after regression analysis adjusting for age, total infused nucleated cell dose, HLA matching to the patient, and comorbidity score. We also investigated whether the lower survival probability and higher cumulative incidence of NRM observed in the dUCB arm of BMT CTN 1101 could be influenced by the TBI 300 cGy patient subset. There was no significant difference in the 1-year incidences of NRM and relapse or in 1-year survival, even after adjustment in multivariate analysis. Patients in BMT CTN 1101 who received TBI 300 cGy and 200 cGy had similar engraftment and early mortality.