Abstract
Donor 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).
We 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 dx . | Time to DCL (mo) . | Age at transplant . | Sex of recipient vs donor Related (y/n) . | Initial cytogenetics . | Demonstration of donor cell origin (cyto,fish, chimerism) . | Outcome . |
|---|---|---|---|---|---|---|
| AML | 4 mo | 25 yo | R=Male D=Female Related=no | 48-57,XY,+Y,+8,+9,9q+,+10, 12p,+14,+15,+19,+21,+1-5 | Cyto = 46,XX FISH=XX Chimerism= 97% donor | Dead Treatment: HyperCVAD OS from diagnosis = 6 mo |
| AML | 5 mo | 49 yo | R=Female D=Male Related=no | 46,XX,t(1;18)(p36.1;q23),del(2) (q31q37) del(8)(q22q24.1), add(11)(p15) | Cyto = 46,XY FISH=XY Chimerism= 100% donor | Dead Treatment: Sorafenib OS from diagnosis = 3 mo |
| AML | 6 mo | 59 yo | R=Female D=Male Related=no | 46,XX,t(1;10;6;11) (p34;q24;q27;q23) | Cyto = 46,XY FISH=XY No MLL seen Chimerism= 92% donor | Dead Treatment: Fludarabine/ cytarabine OS after diagnosis = 2 mo |
| AML | 6 mo | 39 yo | R=Male D=Female Related=no | Diploid male karyotype 46,XY | Cyto = 46,XX Chimerism= 100% donor | Dead Treatment: Fludarabine/ cytarabine/idarubicin OS from diagnosis = 6 mo |
| FL | 103 mo | 49 yo | R=Female D=Female Related=yes | Diploid female karyotype 46,XX | Cyto = 46,XX+8 Chimerism= 93% donor | Alive Treatment: 2nd allo transplant using fludarabine/melphalan OS from diagnosis = 89 mo |
| MCL | 19 mo | 66 yo | R=Male D=Male Related=yes | Diploid male karyotype 46,XY | Cyto =51-56,XY complex with -7 Chimerism= 100% donor | Dead Treatment: Cytarabine/clofarabine OS from diagnosis = 5mo |
| MCL | 36 mo | 62 yo | R=Female D=Female Related=yes | Diploid female karyotype 46,XX | Cyto = 45,XX,t(3;8),-7 Chimerism= 100% donor | Dead Treatment: none OS from diagnosis = 1 mo |
| FL | 50 mo | 63 yo | R=Female D=Male Related=yes | Diploid female karyotype 46,XX | Cyto = 46,XY,-7 Chimerism= 100% donor | Dead Treatment: Cytarabine/idarubicin OS from diagnosis = 5 mo |
| LCL from FL | 43 mo | 59 yo | R=Female D=Male Related=yes | Diploid female karyotype 46,XX | Cyto= 45,XY,-7,del(12)(p13) FISH=XY Chimerism=100% | Alive Treatment:5azacitidine /lenalidomide OS from diagnosis = 4 mo |
| Primary dx . | Time to DCL (mo) . | Age at transplant . | Sex of recipient vs donor Related (y/n) . | Initial cytogenetics . | Demonstration of donor cell origin (cyto,fish, chimerism) . | Outcome . |
|---|---|---|---|---|---|---|
| AML | 4 mo | 25 yo | R=Male D=Female Related=no | 48-57,XY,+Y,+8,+9,9q+,+10, 12p,+14,+15,+19,+21,+1-5 | Cyto = 46,XX FISH=XX Chimerism= 97% donor | Dead Treatment: HyperCVAD OS from diagnosis = 6 mo |
| AML | 5 mo | 49 yo | R=Female D=Male Related=no | 46,XX,t(1;18)(p36.1;q23),del(2) (q31q37) del(8)(q22q24.1), add(11)(p15) | Cyto = 46,XY FISH=XY Chimerism= 100% donor | Dead Treatment: Sorafenib OS from diagnosis = 3 mo |
| AML | 6 mo | 59 yo | R=Female D=Male Related=no | 46,XX,t(1;10;6;11) (p34;q24;q27;q23) | Cyto = 46,XY FISH=XY No MLL seen Chimerism= 92% donor | Dead Treatment: Fludarabine/ cytarabine OS after diagnosis = 2 mo |
| AML | 6 mo | 39 yo | R=Male D=Female Related=no | Diploid male karyotype 46,XY | Cyto = 46,XX Chimerism= 100% donor | Dead Treatment: Fludarabine/ cytarabine/idarubicin OS from diagnosis = 6 mo |
| FL | 103 mo | 49 yo | R=Female D=Female Related=yes | Diploid female karyotype 46,XX | Cyto = 46,XX+8 Chimerism= 93% donor | Alive Treatment: 2nd allo transplant using fludarabine/melphalan OS from diagnosis = 89 mo |
| MCL | 19 mo | 66 yo | R=Male D=Male Related=yes | Diploid male karyotype 46,XY | Cyto =51-56,XY complex with -7 Chimerism= 100% donor | Dead Treatment: Cytarabine/clofarabine OS from diagnosis = 5mo |
| MCL | 36 mo | 62 yo | R=Female D=Female Related=yes | Diploid female karyotype 46,XX | Cyto = 45,XX,t(3;8),-7 Chimerism= 100% donor | Dead Treatment: none OS from diagnosis = 1 mo |
| FL | 50 mo | 63 yo | R=Female D=Male Related=yes | Diploid female karyotype 46,XX | Cyto = 46,XY,-7 Chimerism= 100% donor | Dead Treatment: Cytarabine/idarubicin OS from diagnosis = 5 mo |
| LCL from FL | 43 mo | 59 yo | R=Female D=Male Related=yes | Diploid female karyotype 46,XX | Cyto= 45,XY,-7,del(12)(p13) FISH=XY Chimerism=100% | Alive Treatment:5azacitidine /lenalidomide OS from diagnosis = 4 mo |
9 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).
Our 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)
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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