Haploidentical Transplantation Using T Cell Replete Peripheral Blood Stem Cells and Myeloablative Conditioning in Patients with High-Risk Hematologic Malignancies Who Lack Conventional Donors is Well Tolerated and Produces Excellent Relapse-Free Survival: Results of a Prospective Phase II Trial

Abstract

Haploidentical hematopoietic stem cell transplant (HSCT) provides an opportunity for nearly all patients to benefit from HSCT. We conducted a trial of haploidentical T cell replete allografting using a busulfan-based myeloablative preparative regimen, peripheral blood stem cells (PBSCs) as the graft source, and posttransplantation cyclophosphamide (Cy). Eligibility was limited to patients at high risk of relapse after nonmyeloablative haploidentical bone marrow transplant (BMT). Twenty patients were enrolled in the study (11 with relapsed/refractory disease and 9 who underwent transplantation while in remission and considered standard risk). Donor engraftment occurred in all 20 patients with full donor T cell and myeloid chimerism by day +30. The cumulative incidence of grades II-IV and III-IV acute graft-versus-host disease (aGVHD) was 30% and 10%, respectively. The cumulative incidence of chronic GVHD (cGVHD) was 35%. Nonrelapse mortality (NRM) at 100 days and 1 year was 10% for all patients and 0% for standard-risk patients. With a median follow-up of 20 months, the estimated 1-year overall survival (OS) and disease-free survival (DFS) was 69% and 50%, respectively, for all patients, and 88% and 67% for standard-risk patients. Myeloablative haploidentical HSCT is associated with excellent rates of engraftment, GVHD, NRM, and DFS, and is a valid option in patients with high-risk malignancies who lack timely access to a conventional donor.

Second haploidentical peripheral blood stem cell transplantation for treatment of acute leukemia with relapse after first allogeneic peripheral blood stem cell transplantation

“…The incidence and severity of GVHD in our patients were actually lower than expected, despite the use of PBSC as a stem cell source, as there was no grade 3/4 acute GVHD and only one extensive chronic GVHD. A similar result was reported in the study by Solomon et al, 8 showing that the incidence of acute and chronic GVHD in haploidentical PBSCT using a PTCy strategy was comparable, if not slightly less than expected with allogeneic PBSCT from HLA-matched donors.…”

T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor

“…However, until that study is completed, the evidence hitherto available suggests that Haplo-post-HCT-CY may be associated with superior rates of platelet recovery, NRM, severe acute and chronic GVHD and infection-related mortality than DUCBT. 20,23,[27][28][29][33][34][35] In the parallel phase II studies conducted by the BMT-CTN, DUCBT was associated with a somewhat lower incidence of relapse than Haplo-post-HCT-CY (31% vs 45%). However, relapse risk is very subject to selection bias (for example, the Haplo-post-HCT-CY study included more patients with advanced leukemias) and can only be adequately assessed in the context of a large randomized phase III comparison.…”

Unrelated cord blood compared with haploidentical grafts in patients with hematological malignancies

“…Because of the lack of randomized comparisons, many aspects need to be considered when selecting the most suitable donor, including patient's age, disease status, performance status, and time to transplant. 11,14,[24][25][26][27][28] Currently, we use of several alternatives to HLAidentical donors, such as UCB, mMUD, and haplo transplants. The criteria to select one alternative donor over others are lacking; this creates confusion and introduces high levels of subjectivity into the selection process.…”

“…In addition, haplo-HSCT can be a valid option for patients with a relatively large body weight, for whom an optimal cell dose from UCB is rarely found. [11][12][13][14][15][16] Transplants from a related donor presenting with only a common haplotype with the patient have been the focus of regular but eventually unsuccessful attempts for years. However, severe GVHD and a high incidence of rejection (host-vs-graft effect) have been the major problems encountered when haplo donors, without T-cell depletion, have been initially used after a myeloablative regimen.…”