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Factors associated with improved outcomes after second allogeneic hematopoietic cell transplantation for relapsed pediatric leukemia

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Abstract

A second allogeneic (allo) hematopoietic cell transplant (HCT) is an important therapeutic consideration for patients relapsing after their first. We conducted a retrospective review of 41 pediatric patients with leukemia that underwent a second allo-HCT at our institution. Overall, 53.7 and 43.9 % of patients were alive and disease-free at 1 and 5 years, respectively, after the second allo-HCT. The factors affecting outcome by both univariate and multivariate analysis were interval between transplants and the use of a myeloablative conditioning (MAC) regimen prior to second transplant. Outcomes were inferior in patients who received their second transplant <6 months from their first HCT when compared to patients in whom the interval between HCTs was 6–12 or more than 12 months. Interval between HCTs was also significant when each type of leukemia (acute lymphoblastic leukemia (ALL) n = 21, acute myelogenous leukemia (AML) n = 11, and chronic myelogenous leukemia (CML) n = 7) was analyzed separately. In univariate analysis, use of the same donor and use of a matched sibling donor resulted in significant improved outcome. There was not a significant association between disease-free survival (DFS) and age, remission status, use of total body irradiation (TBI) before second HCT, or type of leukemia. Second allogeneic HCT can be a curative therapeutic option for leukemia patients relapsing after their first transplant. As more targeted therapies have become available, patients that relapse after first HCT are more likely to achieve remission. Therefore, it is anticipated that there will be more candidates for second HCT with improved performance and remission status, ultimately leading to a better outcome with the second HCT.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

Allo:

Allogeneic

AML:

Acute myelogenous leukemia

BM:

Bone marrow

BU:

Busulfan

CI:

Confidence interval

CML:

Chronic myelogenous leukemia

CR:

Complete remission

CY:

Cyclophosphamide

DFS:

Disease-free survival

DLI:

Donor lymphocyte infusions

GvHD:

Graft-versus-host disease

HCT:

Hematopoietic cell transplant

HR:

Hazard ratio

JMML:

Juvenile myelomonocytic leukemia

MAC:

Myeloablative conditioning

MSD:

Matched sibling donor

NRM:

Non-relapse mortality

PBSC:

Peripheral blood stem cells

RIC:

Reduced intensity conditioning

TBI:

Total body irradiation

UCB:

Umbilical cord blood

URD:

Unrelated donor

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Acknowledgments

This work was supported in part by P30 CA023074 from the National Cancer Institute grant and Angel Charity for Children.

Conflict of interest

The authors have no conflicts of interest to disclose.

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    Authors and Affiliations

    1. Department of Pediatrics, University of Arizona, PO Box 245073, 1501 N. Campbell Ave., Tucson, AZ, 85724-5073, USA

      Neethu N. Menon, Lydia M. Jenkins, Andrew M. Yeager & Emmanuel Katsanis

    2. Department of Immunobiology, University of Arizona, Tucson, AZ, USA

      Emmanuel Katsanis

    3. Department of Medicine, University of Arizona, Tucson, AZ, USA

      Craig Jenkins, Faiz Anwer, Andrew M. Yeager & Emmanuel Katsanis

    4. Department of Pathology, University of Arizona, Tucson, AZ, USA

      Emmanuel Katsanis

    5. University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA

      Haiyan Cui, Faiz Anwer, Andrew M. Yeager & Emmanuel Katsanis

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    1. Neethu N. Menon
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    2. Lydia M. Jenkins
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    4. Craig Jenkins
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    Correspondence to Emmanuel Katsanis.

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    Authors’ contributions

    Drs. Menon and LM Jenkins reviewed patient records, compiled the data, and wrote the manuscript. Dr. C Jenkins reviewed the data and co-wrote the manuscript. Dr. Cui reviewed the data, provided the statistical analysis, and wrote part of the paper. Drs. Faiz Anwer and Andrew M Yeager revised the manuscript and provided intellectual content. Dr. Emmanuel Katsanis designed and supervised the study, interpreted the data, and wrote and revised the manuscript. All authors have given final approval of the version to be published and agree to be accountable for all aspects of the work.

    Neethu N. Menon and Lydia M. Jenkins contributed equally to this work.

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    Menon, N.N., Jenkins, L.M., Cui, H. et al. Factors associated with improved outcomes after second allogeneic hematopoietic cell transplantation for relapsed pediatric leukemia. Ann Hematol 95, 637–644 (2016). https://doi.org/10.1007/s00277-016-2599-9

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    • DOI: https://doi.org/10.1007/s00277-016-2599-9

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