High-dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia

Christopher J. Gamper, Clifford M. Takemoto, Allen R. Chen, Heather J. Symons, David M. Loeb, James F. Casella, Amy E. Dezern, Karen Eileen King, Andrea M. McGonigle, Richard J. Jones, Robert A. Brodsky

Research output: Contribution to journalArticle

Abstract

OBJECTIVE:: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression. STUDY DESIGN:: Children and adolescents with SAA who lacked an human leukocyte antigen–matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis. RESULTS:: Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28). CONCLUSIONS:: Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.

Original languageEnglish (US)
JournalJournal of Pediatric Hematology/Oncology
DOIs
StateAccepted/In press - Jul 27 2016

Fingerprint

Aplastic Anemia
Cyclophosphamide
Pediatrics
Antilymphocyte Serum
Cyclosporine
Clonal Evolution
Mycoses
Granulocyte Colony-Stimulating Factor
Therapeutics
Hematopoietic Stem Cells
Bacterial Infections
Immunosuppression
Siblings
Neutrophils
Leukocytes
Survival Rate
Tissue Donors
Transplants
Recurrence
Survival

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Oncology
  • Hematology

Cite this

@article{fdf84092d8f24645bf1d23f31c6cbdfa,
title = "High-dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia",
abstract = "OBJECTIVE:: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression. STUDY DESIGN:: Children and adolescents with SAA who lacked an human leukocyte antigen–matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis. RESULTS:: Overall survival was 85{\%}, with hematologic response of 79{\%} and complete response of 66{\%}. Cumulative incidences of bacterial infection (86{\%}) and fungal infection (62{\%}) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28). CONCLUSIONS:: Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.",
author = "Gamper, {Christopher J.} and Takemoto, {Clifford M.} and Chen, {Allen R.} and Symons, {Heather J.} and Loeb, {David M.} and Casella, {James F.} and Dezern, {Amy E.} and King, {Karen Eileen} and McGonigle, {Andrea M.} and Jones, {Richard J.} and Brodsky, {Robert A.}",
year = "2016",
month = "7",
day = "27",
doi = "10.1097/MPH.0000000000000647",
language = "English (US)",
journal = "Journal of Pediatric Hematology/Oncology",
issn = "1077-4114",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - High-dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia

AU - Gamper, Christopher J.

AU - Takemoto, Clifford M.

AU - Chen, Allen R.

AU - Symons, Heather J.

AU - Loeb, David M.

AU - Casella, James F.

AU - Dezern, Amy E.

AU - King, Karen Eileen

AU - McGonigle, Andrea M.

AU - Jones, Richard J.

AU - Brodsky, Robert A.

PY - 2016/7/27

Y1 - 2016/7/27

N2 - OBJECTIVE:: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression. STUDY DESIGN:: Children and adolescents with SAA who lacked an human leukocyte antigen–matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis. RESULTS:: Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28). CONCLUSIONS:: Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.

AB - OBJECTIVE:: Use of high-dose cyclophosphamide without hematopoietic stem cell transplant to treat severe aplastic anemia (SAA) has been controversial due to concern for increased infectious toxicity as compared with antithymocyte globulin and cyclosporine A. As children often tolerate dose-intensive therapy better than adults, we sought to perform a detailed retrospective analysis of both treatment response and toxicity in 28 patients younger than 22 years of age treated with 29 courses of high-dose cyclophosphamide as the sole form of immunosuppression. STUDY DESIGN:: Children and adolescents with SAA who lacked an human leukocyte antigen–matched sibling donor were treated with cyclophosphamide 50 mg/kg/d for 4 consecutive days then received daily granulocyte colony stimulating factor until neutrophil recovery, transfusion support, and antimicrobial prophylaxis. RESULTS:: Overall survival was 85%, with hematologic response of 79% and complete response of 66%. Cumulative incidences of bacterial infection (86%) and fungal infection (62%) were high but deaths due to infection were rare, as were clonal evolution (1/28), clinically relevant paroxysmal nocturnal (1/28), and relapse (2/28). CONCLUSIONS:: Response rates and survival following high-dose cyclophosphamide in pediatric patients with SAA exceed those seen in adults and compare favorably to antithymocyte globulin/cyclosporine A with manageable infectious toxicity.

UR - http://www.scopus.com/inward/record.url?scp=84979993781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979993781&partnerID=8YFLogxK

U2 - 10.1097/MPH.0000000000000647

DO - 10.1097/MPH.0000000000000647

M3 - Article

C2 - 27467367

AN - SCOPUS:84979993781

JO - Journal of Pediatric Hematology/Oncology

JF - Journal of Pediatric Hematology/Oncology

SN - 1077-4114

ER -