Alternative donor hematopoietic cell transplantation for Fanconi anemia

Margaret L MacMillan, Todd E DeFor, Jo-Anne H Young, Kathryn E Dusenbery, Bruce R Blazar, Arne Slungaard, Heather Zierhut, Daniel J Weisdorf, John E Wagner, Margaret L MacMillan, Todd E DeFor, Jo-Anne H Young, Kathryn E Dusenbery, Bruce R Blazar, Arne Slungaard, Heather Zierhut, Daniel J Weisdorf, John E Wagner

Abstract

Historically, alternative donor hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) patients resulted in excessive morbidity and mortality. To improve outcomes, we made sequential changes to the HCT conditioning regimen. A total of 130 FA patients (median age, 9.0 years; range, 1-48) underwent alternative donor HCT at the University of Minnesota between 1995 and 2012. All patients received cyclophosphamide (CY), single fraction total body irradiation (TBI), and antithymocyte globulin (ATG) with or without fludarabine (FLU), followed by T-cell-depleted bone marrow or unmanipulated umbilical cord blood transplantation. The addition of FLU enhanced engraftment 3-fold. The incidence of grades 2-4 acute and chronic graft-versus-host disease was 20% and 10%, respectively. Severe toxicity was highest in patients >10 years of age or those with a history of opportunistic infections or transfusions before HCT. Mortality was lowest in patients without a history of opportunistic infection or transfusions and who received conditioning with TBI 300 cGy, CY, FLU, and ATG. These patients had a probability of survival of 94% at 5 years. Alternative donor HCT is now associated with excellent survival for patients without prior opportunistic infections or transfusions and should be considered for all FA patients after the onset of marrow failure. These studies were registered at http://www.clinicaltrials.gov as NCT00005898, NCT00167206, and NCT00352976.

© 2015 by The American Society of Hematology.

Figures

Figure 1
Figure 1
Probability of survival after HCT by history of opportunistic infection before HCT.
Figure 2
Figure 2
Probability of survival after HCT by history of transfusions before HCT.
Figure 3
Figure 3
Probability of survival after HCT in patients without a prior history of opportunistic infection or transfusions who received conditioning with TBI 300 cGy and thymic shielding, CY, FLU, and ATG.
Figure 4
Figure 4
Probability of neutrophil recovery by use of fludarabine in the conditioning regimen.

Source: PubMed

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