T Cell-Replete Peripheral Blood Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide Results in Outcomes Similar to Transplantation from Traditionally Matched Donors in Active Disease Acute Myeloid Leukemia.
Outcomes for patients with acute myeloid leukemia (AML) who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there are little data comparing outcomes for AML patients with active disease who receive haploidentical versus traditionally matched HCT. We retrospectively analyzed data from 99 AML patients with active disease undergoing allogeneic HCT at a single institution. Forty-three patients received unrelated donor HCT, 32 patients received matched related donor HCT, and 24 patients received peripheral blood haploidentical HCT with post-transplantation cyclophosphamide. We found no significant differences between treatment groups in terms of overall survival (OS), event-free survival, transplantation-related mortality, cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GVHD). We performed univariate regression analysis of variables that modified OS in all patients and found only younger age at transplantation and development of chronic GVHD significantly improved outcome. Although limited by our relatively small sample size, these results indicate that haploidentical HCT in active AML patients have comparable outcomes to HCT with traditionally matched donors. Haploidentical HCT can be considered in this population of high-risk patients when matched donors are unavailable or when wait times for transplantation are unacceptably long.
How J
，Slade M
，Vu K
，DiPersio JF
，Westervelt P
，Uy GL
，Abboud CN
，Vij R
，Schroeder MA
，Fehniger TA
，Romee R
... -
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Comparison of Outcomes after Peripheral Blood Haploidentical versus Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Myeloid Leukemia: A Retrospective Single-Center Review.
Recent studies comparing allogeneic hematopoietic cell transplantation (HCT) using HLA-matched unrelated donors (MUD) versus HLA-haploidentical donors in patients with acute myeloid leukemia (AML) have suggested equivalent outcomes. The graft source used in most studies of haploidentical transplants has been bone marrow. Similar comparisons between MUD and haplo-HCT using peripheral blood as a graft source have not been adequately performed. We reviewed the records of all 52 AML patients who underwent haplo-HCT (using peripheral blood and post-transplantation high-dose cyclophosphamide) between January 2010 and August 2015 at our institution and compared their outcomes with 88 patients who had a MUD transplant in the same time frame and were frequency matched (preanalysis) to the haploidentical group for conditioning intensity. Multivariate analysis found no difference in outcomes between the 2 groups with the exception of slower count recovery after haploidentical allografts (HR, .48; 95% CI, .32 to .74 for platelets, and HR, .47; 95% CI, .32 to .71 for neutrophils; P < .001 for both comparisons). Our retrospective analysis, although limited by the small sample size, suggests largely similar outcomes with peripheral blood haploidentical versus MUD transplants for AML.
Rashidi A
，DiPersio JF
，Westervelt P
，Vij R
，Schroeder MA
，Cashen AF
，Fehniger TA
，Romee R
... -
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Single Cord Blood Transplantation Versus Unmanipulated Haploidentical Transplantation for Adults with Acute Myeloid Leukemia in Complete Remission.
Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative post-remission therapy for adult patients with acute myeloid leukemia (AML) in complete remission (CR). The availability of alternative human leukocyte antigen (HLA)-mismatched donors, such as cord blood and haploidentical related donors, could allow patients to receive allogeneic HCT who are without an HLA-matched sibling or unrelated donor. The use of these alternative donors is preferable for patients with advanced disease due to the rapid availability. However, comparative data for cord blood transplantation (CBT) and haploidentical related donor transplantation (haplo-HCT) are limited for adult patients with AML in CR. We sought to compare overall survival (OS); leukemia-free survival (LFS); graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS); and chronic GVHD-free, relapse-free survival (CRFS) between single-unit CBT (SCBT) and haplo-HCT recipients for adult patients with intermediate- or poor-risk AML in CR. We retrospectively analyzed and compared the results of allogeneic hematopoietic cell transplantation in 1313 adult patients with intermediate- or poor-risk AML in CR who received either SCBT (n = 1102) or unmanipulated haplo-HCT (n = 211) between 2007 and 2018 in Japan. Among the whole cohort, the cumulative incidences of neutrophil and platelet recovery were significantly lower in SCBT recipients compared with those in haplo-HCT recipients (P < .001 for neutrophil, P < .001 for platelet). SCBT was significantly associated with a higher incidence of grade II to IV acute GVHD and lower incidence of extensive chronic GVHD compared to haplo-HCT (P = .013 for grades II to IV acute GVHD; P = .006 for extensive chronic GVHD). Haplo-HCT recipients developed a higher incidence of cytomegalovirus (CMV) antigenemia compared to SCBT recipients (P = .004). In the multivariate analysis, there were no significant differences for grades III or IV acute GVHD (hazard ratio [HR], 1.17; 95% confidence interval [CI], .88 to 1.57; P = .26), relapse incidence (HR, 1.09; 95% CI, .76 to 1.58; P = .61), non-relapse mortality (HR, .83; 95% CI, .58 to 1.18; P = .32), OS (HR, .92; 95% CI, .70 to 1.20; P = .56), LFS (HR, .94; 95% CI, .73 to 1.21; P = .67), GRFS (HR, 1.12; 95% CI, .90 to 1.40; P = .27), or CRFS (HR, 1.15; 95% CI, .92 to 1.44; P = .19) between the two donor types. In the propensity score matching analysis, which identified 180 patients in each cohort, there were no significant differences in transplant outcomes between the two donor types, except for delayed neutrophil (P < .001) and platelet recovery (P < .001) and a higher incidence of grades II to IV acute GVHD (P = .052) in SCBT. SCBT and unmanipulated haplo-HCT had similar survival outcomes for adult patients with AML in CR despite the lower hematopoietic recovery and higher grade II to IV acute GVHD in SCBT recipients and the higher CMV antigenemia in haplo-HCT recipients.
Konuma T
，Kanda J
，Yamasaki S
，Harada K
，Shimomura Y
，Terakura S
，Mizuno S
，Uchida N
，Tanaka M
，Doki N
，Ozawa Y
，Nakamae H
，Sawa M
，Matsuoka KI
，Morishige S
，Maruyama Y
，Ikegame K
，Kimura T
，Kanda Y
，Ichinohe T
，Atsuta Y
，Yanada M
... -
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Haploidentical Hematopoietic Cell Transplant with Post-Transplant Cyclophosphamide and Peripheral Blood Stem Cell Grafts in Older Adults with Acute Myeloid Leukemia or Myelodysplastic Syndrome.
Many hematologic malignancies are diseases of aging, and the use of hematopoietic cell transplant (HCT) is growing rapidly among older adults. Modern post-transplant cyclophosphamide (PTCy) protocols with haploidentical (haplo) donors have dramatically expanded the donor pool for patients requiring HCT. Initial studies were performed with bone marrow grafts, which require the donor to undergo anesthesia during harvest. However, the use of mobilized peripheral blood stem cells (PBSCs) may be desirable, especially with older donors. However, data on PBSC haplo-HCT in older adults are lacking. To characterize the impact of age on outcomes in haplo-HCT, we identified all adult patients undergoing haplo-HCT with PTCy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) at our institution from January 2009 to June 2016. Patients were grouped into 3 cohorts: Age 1 (≤55), Age 2 (55 to 65), and Age 3 (≥65). To characterize the impact of donor type on outcomes in older patients, we identified age- and disease risk index (DRI)-matched patient age ≥ 65 undergoing HLA-matched unrelated donor (MUD) HCT for AML or MDS during the same time frame. Patients were scored for disease risk and underlying comorbidities using the DRI and HCT-specific comorbidity index. Overall survival (OS) was analyzed using 3 different Cox proportional hazards models. We identified 112 haplo-HCT patients, 95 with AML and 17 with MDS. There were 61 patients in Age 1, 29 patients in Age 2, and 22 in Age 3. Median OS was 448, 397, and 147 days in Age 1, Age 2, and Age 3 patients (log-rank, P = .04). After adjusting for other risk factors, age ≥ 65 was associated with significantly worse OS after haplo-HCT (aHR, 2.16; 95% CI, 1.15 to 4.07). There was a trend toward increased relapse among older patients at 2 years (56%; 95% CI, 32% to 79%) versus Age 1 (41%; 95% CI, 28% to 54%) and Age 2 (31%; 95% CI, 12% to 50%) (P = .08). Among patients age ≥ 65, donor type (MUD versus haplo) did not impact OS (aHR, 1.03; 95% CI, .56 to 1.88) after adjusting for other risk factors. Prior allo-HCT (aHR, 4.95; 95% CI, 1.82 to 13.49) and myeloablative conditioning (aHR, 1.97; 95% CI, 1.04 to 3.73) were associated with inferior survival. Although age ≥ 65 was associated with inferior OS in our haplo-HCT cohort, no difference was seen in survival between MUD and haplo-HCT. Therefore, the use of haploidentical donors in older patients is a reasonable treatment option, especially if there is concern for clinical deterioration. A careful pretransplant evaluation and analysis of risks and benefits is warranted when offering this transplant modality to older adults, especially in patients with previous transplant or poor performance status. Strategies to reduce the risk of relapse and decrease nonrelapse mortality in older adults are areas of ongoing research, and prospective studies are needed.
Slade M
，DiPersio JF
，Westervelt P
，Vij R
，Schroeder MA
，Romee R
... -
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