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Rarity of Donor-Derived Malignancy after Allogeneic BMT with High-Dose Post-Transplantation Cyclophosphamide
Poster Abstracts
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Huzefa Mogri, BS
,
Johns Hopkins Medical Institution, Baltimore, MD
Jennifer A. Kanakry, MD
,
Oncology, Sidney Kimmel Cancer Center, Johns hopkins University, Baltimore, MD
Richard Ambinder, MD, PhD
,
Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
Leo Luznik, MD
,
Hematologic Malignancies/Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Ephraim Fuchs, MD
,
Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Richard J. Jones, MD
,
Department of Oncology, The Johns Hopkins University, Baltimore, MD
Yvette L. Kasamon, MD
,
Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD
Donor-derived malignancy (DDM) is a rare but often fatal complication
of alloBMT, with a reported incidence of 0.1-5%. AlloBMT utilizing high-dose
post-transplantation cyclophosphamide (PT/Cy) as GVHD prophylaxis produces
excellent rates of engraftment and low rates of acute and chronic GVHD. Because
exposing the allograft to
cytotoxic chemotherapy may theoretically
increase the risk of DDM, we evaluated the incidence of DDM after alloBMT with PT/Cy.
From 2000-2012, 790 patients (median age 51y, range 1-74y) received T-cell
replete alloBMT with high-dose PT/Cy at Johns Hopkins, including 313 (40%) who
received PT/Cy as sole GVHD prophylaxis. Of these transplants, 349 (44%) were HLA-
haploidentical and 346 (44%) were myeloablative. Median donor age was 41y (range 13-79y). With
a median follow-up of 3y (range, 0.8-9.4y) in patients without events, the 3
year PFS and OS probabilities were 42% and 56% respectively. Five cases (5/790=0.6%)
of DDM were identified as well as one case of
clonal,
donor-derived LGL leukemia that resolved without any therapy. By competing-risk
analysis, the probability of DDM was 0.6% at 1 y, 0.8% at 5 y, and 2% overall
(Figure). In the 5 identified cases of
DDM, the median patient age was 41y (range 18-65 y) at BMT and median donor age
was 41y (31-67y). These patients were
initially transplanted for ALL (1), NHL (3), or Hodgkin lymphoma (1). Two
patients received
myeloablative conditioning and 3
received additional GVHD prophylaxis with mycophenolate mofetil and tacrolimus.
The median time from BMT to the diagnosis of DDM was 1.3y (range 0.5-6.3y). DDMs consisted of MDS (1), AML (3), and CMML (1).
All of the patients received treatment for their DDM; 2 are long term survivors
and 3 died of their DDM. The incidence of developing a DDM after high-dose
PT/Cy is rare, and is within the range reported for other transplant platforms.
Disclosures:
H. J. Symons,
Otsuka Pharmaceuticals, none: Otsuka supports a clinical trial of mine that helps fund research nursing and data management only and Research Funding
R. J. Jones,
Aldagen, Hold patent on Aldefluor: Royalty
