Background

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).

Methods

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 dxTime to DCL (mo)Age at transplantSex 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 dxTime to DCL (mo)Age at transplantSex 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 
Results

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).

Conclusions

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)

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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