Development of Donor Cell Derived Leukemia After Allogeneic Stem Cell Transplant

Abstract

BackgroundDonor cell derived leukemia (DCL) is a rare event after allogeneic stem cell transplantation. First described in 1971, several cases of acute myeloid leukemia (AML) or myelodysplasia (MDS) arising from donor cells have been reported. The true incidence of DCL is difficult to ascertain, however the European Group for Blood and Marrow Transplantation survey reported in 2005 an estimated rate of 124 cases per 100,000 transplants (Hernstein et al., Hematologica 2005;90:969-975). The aim of our study was to determine the incidence and natural history of DCL after allogeneic stem cell transplantation (allo-HCT). MethodsWe retrospectively reviewed patients that received an allo-HCT at MD Anderson from 1/1997 to 6/2012 for hematologic malignancy (n=2148) and chose to study two groups: (1) patients who had a sex mismatched allo-HCT for AML /MDS (n=433) and (2) those who received an allo-HCT for non-hodgkins lymphoma (NHL) (n=773) – subsequently these cases were reviewed for a diagnosis of AML/MDS post transplant. Donor origin of leukemic cells was confirmed by presence of donor specific sex chromosomes on conventional cytogenetic analysis or FISH studies and by donor specific microsatellite polymorphic markers on DNA analysis (chimerism studies). Demographic and disease-related data are presented in table 1.Primary dxTime to DCL (mo)Age at transplantSex of recipient vs donorRelated (y/n)InitialcytogeneticsDemonstration of donor cell origin (cyto,fish, chimerism)OutcomeAML4 mo25 yoR=MaleD=FemaleRelated=no48-57,XY,+Y,+8,+9,9q+,+10,12p,+14,+15,+19,+21,+1-5Cyto = 46,XXFISH=XXChimerism= 97% donorDeadTreatment: HyperCVADOS from diagnosis = 6 moAML5 mo49 yoR=FemaleD=MaleRelated=no46,XX,t(1;18)(p36.1;q23),del(2)(q31q37) del(8)(q22q24.1), add(11)(p15)Cyto = 46,XYFISH=XYChimerism= 100% donorDeadTreatment: SorafenibOS from diagnosis = 3 moAML6 mo59 yoR=FemaleD=MaleRelated=no46,XX,t(1;10;6;11)(p34;q24;q27;q23)Cyto = 46,XYFISH=XYNo MLL seenChimerism= 92% donorDeadTreatment:Fludarabine/ cytarabineOS after diagnosis = 2 moAML6 mo39 yoR=MaleD=FemaleRelated=noDiploid male karyotype 46,XYCyto = 46,XXChimerism= 100% donorDeadTreatment: Fludarabine/ cytarabine/idarubicinOS from diagnosis = 6 moFL103 mo49 yoR=FemaleD=FemaleRelated=yesDiploid female karyotype 46,XXCyto = 46,XX+8Chimerism= 93% donorAliveTreatment: 2nd allo transplant using fludarabine/melphalanOS from diagnosis = 89 moMCL19 mo66 yoR=MaleD=MaleRelated=yesDiploid male karyotype 46,XYCyto =51-56,XY complex with -7Chimerism= 100% donorDeadTreatment:Cytarabine/clofarabineOS from diagnosis = 5moMCL36 mo62 yoR=FemaleD=FemaleRelated=yesDiploid female karyotype 46,XXCyto = 45,XX,t(3;8),-7Chimerism= 100% donorDeadTreatment: noneOS from diagnosis = 1 moFL50 mo63 yoR=FemaleD=MaleRelated=yesDiploid female karyotype 46,XXCyto = 46,XY,-7Chimerism= 100% donorDeadTreatment:Cytarabine/idarubicinOS from diagnosis = 5 moLCL from FL43 mo59 yoR=FemaleD=MaleRelated=yesDiploid female karyotype 46,XXCyto= 45,XY,-7,del(12)(p13)FISH=XYChimerism=100%AliveTreatment:5azacitidine/lenalidomideOS from diagnosis = 4 mo Results9 cases of DCL were identified out of 1206 allo-HCTs done (0.7%) from 1997-2012. 4 cases were patients who received sex mismatched allo-HCTs for AML/MDS while the other 5 were patients after allo-HCT for NHL. Median age at transplant was 59 years (range 25-66 years) and median time to diagnosis of DCL was 19 months (range 4-103 months). Only 1 patient was actively treated for GVHD with corticosteroids at diagnosis of DCL. Four of 9 had monosomy 7, 1 of 9 had trisomy 8 while the remainder of patients had diploid cytogenetics. The outcome of DCL was poor with a median survival from diagnosis of 5 months (range 1-89 months). ConclusionsOur analysis suggests that DCL occurs in no less than 0.7% of patients receiving allogeneic stem cell transplants for AML/MDS or NHL. While the mechanism of leukemogenesis is unclear, monosomy 7 was demonstrated in 45% of these cases. Although the number of cases analyzed is low, the overall prognosis for DCL seems poor.Cytogenetics (cyto) Recipient (R) Donor (D) Follicular lymphoma (FL) Mantle cell lymphoma(MCL) Large cell lymphoma(LCL) Overall survival (OS) Disclosures:No relevant conflicts of interest to declare.