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 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 appeared with median of 10 months 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 and with sex mismatch. 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 long-term DCL survivors remain full chimeras and did not needed 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 "do novo" leukemias employing combined chemotherapy.