Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia

Reinhold Munker; Ruta Brazauskas; Hai Lin Wang; Marcos de Lima; Hanna J. Khoury; Robert Peter Gale; Richard T. Maziarz; Brenda M. Sandmaier; Daniel Weisdorf; Wael Saber

doi:10.1016/j.bbmt.2016.02.013

Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia

Reinhold Munker
, Ruta Brazauskas
, Hai Lin Wang
, Marcos de Lima
, Hanna J. Khoury
, Robert Peter Gale
, Richard T. Maziarz
, Brenda M. Sandmaier
, Daniel Weisdorf
, Wael Saber

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67% (95% confidence interval [CI], 57 to 76), leukemia-free survival of 56% (95% CI, 46 to 66), relapse incidence of 29% (95% CI, 20 to 38), and nonrelapse mortality of 15% (95% CI, 9 to 23) were encouraging. OS was best in younger patients (<20 years), but no significant differences were observed between those 20 to 40 years of age and those who were 40 years or older. A matched-pair analysis showed similar outcomes comparing MPAL cases to 375 acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft-versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival.

Original language	English
Pages (from-to)	1024-1029
Number of pages	6
Journal	Biology of Blood and Marrow Transplantation
Volume	22
Issue number	6
DOIs	https://doi.org/10.1016/j.bbmt.2016.02.013
State	Published - Jun 1 2016

Bibliographical note

Publisher Copyright:
© 2016 The American Society for Blood and Marrow Transplantation.

Funding

The CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID) ; a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI ; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS) ; 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research ; and grants from * Actinium Pharmaceuticals ; Allos Therapeutics, Inc. ; * Amgen, Inc. ; anonymous donation to the Medical College of Wisconsin ; Ariad ; Be the Match Foundation ; * Blue Cross and Blue Shield Association ; * Celgene Corporation ; Chimerix, Inc. ; Fred Hutchinson Cancer Research Center ; Fresenius-Biotech North America, Inc. ; * Gamida Cell Teva Joint Venture Ltd. ; Genentech, Inc. ; * Gentium SpA ; Genzyme Corporation ; GlaxoSmithKline ; Health Research, Inc. ; Roswell Park Cancer Institute ; HistoGenetics, Inc. ; Incyte Corporation ; Jeff Gordon Children's Foundation ; Kiadis Pharma ; The Leukemia & Lymphoma Society ; Medac GmbH ; The Medical College of Wisconsin ; Merck & Co, Inc. ; Millennium: The Takeda Oncology Co. ; * Milliman USA, Inc. ; * Miltenyi Biotec, Inc. ; National Marrow Donor Program ; Onyx Pharmaceuticals ; Optum Healthcare Solutions, Inc. ; Osiris Therapeutics, Inc. ; Otsuka America Pharmaceutical, Inc. ; Perkin Elmer, Inc. ; * Remedy Informatics ; * Sanofi US ; Seattle Genetics ; Sigma-Tau Pharmaceuticals ; Soligenix, Inc. ; St. Baldrick's Foundation ; StemCyte , A Global Cord Blood Therapeutics Co. ; Stemsoft Software, Inc. ; Swedish Orphan Biovitrum ; * Tarix Pharmaceuticals ; * TerumoBCT ; * Teva Neuroscience, Inc. ; * THERAKOS, Inc. ; University of Minnesota ; University of Utah ; and * Wellpoint, Inc. . The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the US Government.

Funders	Funder number
Allos Therapeutics, Inc.
Teva Neuroscience, Inc.
Office of Naval Research Naval Academy
U.S. Department of Health and Human Services	N00014-13-1-0039, N00014-14-1-0028
National Heart, Lung, and Blood Institute (NHLBI)	U01HL069294
National Childhood Cancer Registry – National Cancer Institute
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	HHSH250201200016C
Health Resources and Services Administration
AMGen
University of Utah
Actinium Pharmaceuticals Incorporated
Kiadis Pharma

Keywords

Acute biphenotypic leukemia
Allogeneic transplantation
Mixed phenotype leukemia

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2016.02.013

Cite this

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title = "Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia",

abstract = "Acute biphenotypic leukemias or mixed phenotype acute leukemias (MPAL) are rare and considered high risk. The optimal treatment and the role of allogeneic hematopoietic stem cell transplantation (alloHCT) are unclear. Most prior case series include only modest numbers of patients who underwent transplantation. We analyzed the outcome of 95 carefully characterized alloHCT patients with MPAL reported to the Center for International Blood and Marrow Transplant Research between 1996 and 2012. The median age was 20 years (range, 1 to 68). Among the 95 patients, 78 were in first complete remission (CR1) and 17 were in second complete remission (CR2). Three-year overall survival (OS) of 67\% (95\% confidence interval [CI], 57 to 76), leukemia-free survival of 56\% (95\% CI, 46 to 66), relapse incidence of 29\% (95\% CI, 20 to 38), and nonrelapse mortality of 15\% (95\% CI, 9 to 23) were encouraging. OS was best in younger patients (<20 years), but no significant differences were observed between those 20 to 40 years of age and those who were 40 years or older. A matched-pair analysis showed similar outcomes comparing MPAL cases to 375 acute myelogenous leukemia or 359 acute lymphoblastic leukemia cases. MPAL patients had more acute and a trend for more chronic graft-versus-host disease. No difference was observed between patients who underwent transplantation in CR1 versus those who underwent transplantation in CR2. AlloHCT is a promising treatment option for pediatric and adult patients with MPAL with encouraging long-term survival.",

keywords = "Acute biphenotypic leukemia, Allogeneic transplantation, Mixed phenotype leukemia",

author = "Reinhold Munker and Ruta Brazauskas and Wang, \{Hai Lin\} and \{de Lima\}, Marcos and Khoury, \{Hanna J.\} and Gale, \{Robert Peter\} and Maziarz, \{Richard T.\} and Sandmaier, \{Brenda M.\} and Daniel Weisdorf and Wael Saber",

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AU - Brazauskas, Ruta

AU - Wang, Hai Lin

AU - de Lima, Marcos

AU - Khoury, Hanna J.

AU - Gale, Robert Peter

AU - Maziarz, Richard T.

AU - Sandmaier, Brenda M.

AU - Weisdorf, Daniel

AU - Saber, Wael

PY - 2016/6/1

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Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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