T-Cell–Depleted Allogeneic Bone Marrow Transplantation as Postremission Therapy for Acute Myelogenous Leukemia: Freedom From Relapse in the Absence of Graft-Versus-Host Disease

Abstract

Thirty-one consecutive patients with acute myelogenous leukemia (AML) in first complete remission and 8 with AML in second complete remission received T cell–depleted allogeneic bone marrow transplants from HLA-identical sibling donors. Patients received myeloablative cytoreduction consisting of hyperfractionated total body irradiation, thiotepa, and cyclophosphamide. Those patients at risk for immune-mediated graft rejection received additional immune suppression with antithymocyte globulin and methylprednisolone in the early peritransplant period. Patients with AML who underwent allogeneic T-cell–depleted bone marrow transplantations (BMT) in first or second remission have achieved respective disease-free survival (DFS) probabilities of 77% (median follow-up at approximately 56 months) and 50% (median follow-up at approximately 48 months). Ten of 31 patients transplanted in first remission were ≥ 40 years old and have attained a DFS at 4 years of 70%. For patients with AML transplanted in first or second remission, the respective cause-specific probabilities of relapse were 3.2% or 12.5%, and those of nonleukemic mortality were 19.4% or 37.5%. There were no cases of immune-mediated graft rejection and no cases of grade II to IV acute graft-versus-host disease (GVHD). All survivors enjoy Karnofsky performance scores (KPS) of 100%, except 2 patients with KPS of 80% to 90%. T-cell–depleted allogeneic BMT can provide durable DFS together with an excellent performance status in the majority of patients with de novo AML. In addition, GVHD is not an obligatory correlate of the graft-versus-leukemia benefit or freedom from relapse afforded by allogeneic BMT administered as postremission therapy for AML. This study provides a basis for prospective comparison with other postremission therapies considered standard in the management of patients with this disease.

Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Patients with Treatment-Related Myelodysplastic Syndrome or Acute Myelogenous Leukemia

“…The concern for increased relapse rates in patients with MDS/AML treated with TCD transplantations has been raised in the medical literature. As described previously, however, the results of TCD transplantations from our institution for MDS or AML have been associated with a relapse rate comparable to that of unmodified transplantations [28]. Moreover, in this high-risk population, we found an incidence of relapse of 19%, which is lower than that previously described in the literature [10,13,14].…”

Pre‐ and post‐engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients

“…Supportive care and standard prophylaxis against opportunistic infections for HSCT recipients at MSKCC have been previously described (19). Prophylaxis for Pneumocystis included trimethoprim (TMP)/sulfamethoxazole (SMZ) (TMP 10 mg/kg/day) from day − 7 through day − 3.…”

Checkpoint inhibitors in AML: are we there yet?

“…Since the greatest concern in the use of immune checkpoints is development of uncontrollable GVHD, alloHCT platforms with low GVHD potential could be used. In vivo and in vitro T cell depleted alloHCT are associated with lower incidence of acute and chronic GVHD (Papadopoulos et al , ; Jakubowski et al , ; Jakubowski et al , ; Barba et al , ; Malard et al , ; Cho & Perales, ) (Papadopoulos et al , ; Jakubowski et al , ; Jakubowski et al , ). Further studies will be required to identify the optimal treatment combinations with checkpoint inhibitors in AML as well as their use in the context of alloHCT.…”