Theresa Donohue

Long-term persistence of nonpathogenic clonal chromosome abnormalities in donor hematopoietic cells after allogeneic stem cell transplantation.

We describe the cases of two unrelated patients who exhibited multiple chromosomal abnormalities in donor cells after allogeneic peripheral blood stem cell transplantation (PBSCT). The patients were diagnosed with chronic myeloid leukemia and chronic lymphocytic leukemia, respectively, and both underwent nonmyeloablative conditioning with cyclophosphamide and fludarabine followed by PBSCT from their HLA-matched opposite-sex siblings. Post-transplant bone marrow cytogenetics showed full engraftment, and the early post-transplant studies demonstrated only normal donor metaphases. Subsequent studies of both patients, however, revealed a population of metaphase cells with abnormal, but apparently balanced, donor karyotypes. Chromosome studies performed on peripheral blood cells collected from both donors after transplantation were normal. Both patients remained in clinical remission during follow-up of approximately 8 years in one case, and 6 years in the other case, despite the persistence of the abnormal clones. Chromosomal abnormalities in residual recipient cells after bone marrow or PBSCT are not unusual. In contrast, only rare reports of chromosome abnormalities in donor cells exist, all of which have been associated with post-bone marrow transplant myelodysplastic syndrome or acute leukemias. The present cases demonstrate the rare phenomenon of persistent clonal nonpathogenic chromosome aberrations in cells of donor origin.

Rapid donor T-cell engraftment increases the risk of chronic graft-versus-host disease following salvage allogeneic peripheral blood hematopoietic cell transplantation for bone marrow failure syndromes

The risk of graft‐rejection after allogeneic hematopoietic cell transplantation using conventional cyclophosphamide‐based conditioning is increased in patients with bone marrow failure syndromes (BMFS) who are heavily transfused and often HLA‐alloimmunized. Fifty‐six patients with BMFS underwent fludarabine‐based reduced‐intensity conditioning and allogeneic peripheral blood progenitor cell (PBPC) transplantation at a single institution. The conditioning regimen consisted of intravenous cyclophosphamide, fludarabine, and equine antithymocyte globulin. Graft‐versus‐host disease (GVHD) prophylaxis included cyclosporine A alone or in combination with either mycophenolate mofetil or methotrexate. To reduce the risk of graft‐rejection/failure, unmanipulated G‐CSF mobilized PBPCs obtained from an HLA‐identical or single HLA‐antigen mismatched relative were transplanted rather than donor bone marrow. Despite a high prevalence of pretransplant HLA‐alloimmunization (41%) and a heavy prior transfusion burden, graft‐failure did not occur with all patients having sustained donor lympho‐hematopoietic engraftment. The cumulative incidence of grade II–IV acute‐GVHD and chronic‐GVHD was 51.8% and 72%, respectively; with 87.1% surviving at a median follow‐up of 4.5 years. A multivariate analysis showed pretransplant alloimmunization and rapid donor T‐cell engraftment (≥95% donor by day 30) were both significantly (P < 0.05) associated with the development of chronic‐GVHD (adjusted HR 2.13 and 2.99, respectively). These data show fludarabine‐based PBPC transplantation overcomes the risk of graft‐failure in patients with BMFS, although rapid donor T‐cell engraftment associated with this approach appears to increase the risk of chronic‐GVHD. (Clinicaltrials.gov identifier: NCT00003838). Am. J. Hematol. 88:874–882, 2013.

Successful Use of Balloon Ablation to Treat Menorrhagia Complicating Aplastic Anemia

Background: Aplastic anemia (AA) complicated by menorrhagia is treated with transfusion and hormonal therapy. When bleeding is life-threatening, balloon endometrial ablation can safely be used to treat menorrhagia in selected patients. Case: A 56-year-old postmenopausal woman was diagnosed with AA after several weeks of menorrhagia and pancytopenia. She became heavily alloimmunized after extensive platelet transfusion. During treatment with antithymocyte globulin, vaginal bleeding increased and the platelet count fell to 1,000/µl on supportive measures. After bleeding stopped with use of intravenous Premarin, she was examined in the operating room. There, a clot was removed and appeared to be a uterine caste; hemostasis continued. Transvaginal ultrasound revealed a normal endometrial contour and thin endometrium; endometrial histology was benign. After she completed antithymocyte globulin and her platelet count could be maintained over 30,000/µl with matched platelets, endometrial ablation was performed without any complications. Conclusion: Thermal balloon endometrial ablation is an effective alternative to hysterectomy for women with persistent menorrhagia and AA when supportive measures fail. Prior to endometrial ablation, evaluation should ensure normal endometrial contour and histology, and that sufficient blood products are available to maintain platelet counts above 30,000/µl during the healing process.