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Clinical Trial
. 2018 Oct;24(10):2034-2039.
doi: 10.1016/j.bbmt.2018.06.007. Epub 2018 Jun 14.

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide/Bendamustine in Pediatric and Young Adult Patients with Hematologic Malignancies

Emmanuel Katsanis  1 , Lauren N Sapp  2 , Nicole Varner  3 , Shannon Koza  4 , Baldassarre Stea  5 , Yi Zeng  6
Affiliations
Clinical Trial

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide/Bendamustine in Pediatric and Young Adult Patients with Hematologic Malignancies

Emmanuel Katsanis et al. Biol Blood Marrow Transplant. 2018 Oct.

Abstract

More than half of patients undergoing hematopoietic cell transplantation at our institution are ethnic or racial minorities, making the search for matched unrelated donors more challenging. Since the introduction of haploidentical bone marrow transplant (haplo-BMT) into our pediatric BMT program in 2015, 69.2% of recipients have been minorities. Herein, we describe our experience with the first 13 pediatric and young adult patients with hematologic malignancies who have undergone T cell-replete haplo-BMT after myeloablative conditioning (MAC) at our institution. We have previously documented that in experimental haplo-BMT, post-transplant bendamustine (PT-BEN) is at least as effective as post-transplant cyclophosphamide (PT-CY) against graft-versus-host disease (GVHD) and elicits superior graft-versus-leukemia (GVL) effects. We report on, for the first time in humans, 4 patients treated with PT-CY and PT-BEN after haplo-BMT as part of our ongoing institutional phase I/II study (NCT02996773). The remaining 9 patients reviewed in this report received PT-CY. Our findings indicate that MAC haplo-BMT is well tolerated by children and young adults with advanced hematologic malignancies with no observed nonrelapse mortality or grades III to IV GVHD. All patients who underwent haplo-BMT remain alive and disease-free with a median follow-up of 15.6 months (range, 1.5 to 31.2). Preliminary findings from our ongoing clinical trial demonstrate that partial substitution of PT-BEN for PT-CY is feasible and safe after haplo-BMT as an immune modulatory strategy to alleviate GVHD and potentially more effectively preserve GVL.

Keywords: Haploidentical BMT; PT-bendamustine; PT-cyclophosphamide.

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Conflict of interest statement

Conflict of interest disclosure

There are no conflicts of interest, financial or otherwise, involving any of the authors regarding the submission or publication of this manuscript.

Figures

Figure. 1
Figure. 1
Time to an absolute neutrophil count (ANC) of 500. Time in days from haplo-BMT to achieving an ANC of at least 0.5 × 109/L. Defined as the first of three consecutive days with an ANC of 0.5 × 109/L. PT-CY vs PT-BEN P=ns
Figure. 2
Figure. 2
Time to a platelet count of 20,000. Time in days from haplo-BMT to achieving a platelet count of at least 20 × 109/L. Defined as the first of three consecutive days with platelet counts of ≥20 × 109/L with no platelet transfusions administered in the previous 7 days. PT-CY vs PT-BEN P=ns
Figure. 3
Figure. 3
Cumulative incidences of grades II to IV and grades III to IV acute GVHD
Figure. 4
Figure. 4
Two-year probability estimates of all chronic GVHD and of extensive cGVHD
Figure. 5
Figure. 5
Kaplan-Meier DFS of all patients receiving haplo-BMT
See this image and copyright information in PMC

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