Abstract
Leukemia relapse occurring in donor cells, so called donor cell leukemia (DCL) after allogeneic hematopoietic stem cell transplantation has been previously reported in the literature. Some authors have suggested that the development of DCL is perhaps a more common occurrence than traditionally thought. Donor cell myeloma (DCM) seems to be less frequent than DCL. This 46-year old male when first seen in 2000 was diagnosed with stage IIIa multiple myeloma. A monoclonal IgA kappa spike was recorded at diagnosis. Treatment with melphalan and prednisone was delivered every four to six weeks for a total of 22 courses. Fourty months after the initial diagnosis, an M2 acute myelogenous leukemia was identified. Treatment with chemotherapy resulted in complete remission. Matched UCB cells were localized at the London Cord Blood Bank. The UCB belonged to a male product of a white western European mother and a black Nigerian father who was a carrier of hemoglobin S. Hemoglobins A, F and S were detected in the UCB, consonant with sickle cell trait. The patient was allografted employing the "Mexican" NST conditioning regimen, granulocyte count recovered to more than 0.5 x 109/L on day 14, with the platelet count never dropping below 20 x 109/L. On day +40, the polymorphic microsatellite markers revealed mixed chimerism. The hemoglobin S gene was identified on day +20 and on day +60, full chimerism was shown. Cyclosporine A was stopped on day +350. The patient returned 170 months after the transplant with low back pain and the bone marrow aspiration disclosed 80% abnormal plasma cells, an IgA kappa monoclonal spike of 3.1 gr/dl, and complete chimerism. Malignant plasma cells were sorted by means of flow cytometry before genetic fingerprinting; cells were stained with an admixture of fluorescent monoclonal antibodies and cells co-expressing dim CD45, bright CD38 and CD56 were sorted out to ≥99% purity. Sorted cells were shown to have donor origin (Figure 1). The patient was treated with thalidomide, dexamethasone and bortezomib and the monoclonal spike disappeared; an autologous stem cell transplant is planned. Most people consider that the development of a malignancy in the cells of the donor is a rare event and very few prospective studies have analyzed the real prevalence of this phenomenon. Prospectively, we have found that 7% (95% CI 2.9 to 13.6%) of patients with leukemic activity after an allogeneic graft do have a donor cell-derived leukemia; this figure contrasts with those described elsewhere in non-prospective studies. A major problem in the analysis of donor cell derived malignancies is that demonstration of the donor cell origin of malignant activity. In this case, the demonstration of DNA of the donor in the fluorescence-activated sorted malignant plasma cells is indicative of the origin of the myeloma cells. Interestingly, the immunoglobulin type produced by the initial myeloma cells is the same as that of the donor-cell myeloma; Despite being two myelomas producing the same immunoglobulin subtype, both should be considered as de novomalignancies and as such, treated; we have previously shown that donor cell leukemias do have a response when treated as de novo, non-secondary leukemias. To our best knowledge, this is the second report of DCM following allogeneic HSCT. Prior to this case, Kim et al reported a DCM after an allogeneic transplant in a patient with refractory anemia with ringed sideroblasts. Previously, two cases have been reported of donor-origin MM, but they occurred in patients who underwent solid organ transplantation of the kidney and heart-lung. Kumar et alreported a case of DCM developing after unrelated allogeneic HSCT in the both donor and recipient but they did not conducted a comprehensive molecular cytogenetic study. In the case published by Maestas et al, an abnormal proliferation of plasma cells was identified in the donor, thus making possible that a malignant plasma cell clone was already present in the donor stem cells. In summary, we have clearly shown that this patient has had three different malignancies: 1) De novomultiple myeloma, 2) Secondary acute myelogenous leukemia and 3) De novodonor cell-derived multiple myeloma. The mechanisms involved in these episodes could be useful to better understand tumorigenesis.
No relevant conflicts of interest to declare.
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