Donor Cell Leukemia: A Prospective Study of Its Identification and Treatment

Leukemia relapses occurring in donor cells, so called donor cell leukemias (DCL) after allogeneic hematopoietic stem cell transplantation have been reported in several cases and still are considered as rare diseases. Cytogenetic analysis, flow cytometry and molecular testing have been used to confirm this event in the cases so far reported. The etiology of DCL is unclear, and the reported literature does not suggest a common mechanism. The incidence of this condition is largely unknown, as well as the results of its treatment. We have prospectively searched for DCL in a 12-year period, in a single institution. In a group of 106 consecutive patients allografted because of leukemia; we have identified 7 cases of DCL; six of them were allografted because of relapsed acute lymphoblastic leukemia (ALL) and one because of paroxysmal nocturnal hemoglobinuria / aplastic anemia; these figures suggest that the real incidence of DCL has been underestimated in previous studies. All the patients were allografted from HLA-identical siblings, employing a reduced-intensity conditioning regimen. The cases of DCL appeared one to 40 months (median 10) after the allograft; the number of blast cells when the leukemic activity ensued was above 50% in all cases, whereas the chimerism studies revealed more than 90% cells of donor origin. The origin of the leukemia cells was shown by microsatellites in all cases and in three with a sex mismatch it was confirmed by the enumeration of XX / XY cells in the leukemic cells. The six patients with lymphoblastic DCL were treated prospectively with a pediatric-inspired combined chemotherapy schedule designed for “de novo” ALL patients. A complete response was obtained in 3/6 patients with lymphoblastic DCL these patients being alive in a complete remission at 11, 12 and 98 months after the diagnosis of DCL. The patient with hairy cell DCL has had a benign course, not needing any treatment. In the whole group the median survival (SV) has not been reached, the overall SV being 57% at 98 months. The long-term DCL survivors remain full chimeras and did not need a second transplant. It is concluded that the prevalence of DCL may be higher if it is prospectively looked for, and that acceptable therapeutic results are obtained if patients are treated as “de novo” leukemias employing combined chemotherapy.