In vivo alemtuzumab enables haploidentical human leukocyte antigen-mismatched hematopoietic stem-cell transplantation without ex vivo graft manipulation.

BACKGROUND: Alemtuzumab, a humanized monoclonal antibody directed against human CD52, has a strong lympholytic effect. This study evaluates the safety of unmanipulated peripheral blood stem-cell transplantation from two or three loci-mismatched related donors using alemtuzumab in vivo. METHODS: A total body irradiation-based regimen was used in young patients, whereas those 50 years or older received fludarabine-based conditioning. Alemtuzumab was added to these regimens by intravenous infusion at 0.2 mg/kg per day for 6 days (days -8 to -3). RESULTS: We treated 12 patients with a median age of 49.5 years. Eight patients demonstrated active disease, and four patients demonstrated acute leukemia in high-risk remission. All achieved neutrophil engraftment a median of 17.5 days after transplantation with complete donor-type chimerism. The cumulative incidence of grades III to IV acute graft-versus-host disease was only 9%. Infection-related deaths were not observed. CD3+/CD4+ and CD3+/CD8+ T cells were strongly suppressed within 2 months after transplantation, but recovered on day 90. Relapse was observed in five of eight patients who underwent transplantation for active disease, whereas none of the three patients who underwent transplantation in first remission had a relapse. CONCLUSIONS: We conclude that in vivo alemtuzumab enables haploidentical hematopoietic stem-cell transplantation without ex vivo graft manipulation.

Clinical significance of peripheral blood erythroblastosis after hematopoietic stem cell transplantation.

Erythroblasts (EBL) are normally not observed in peripheral blood, but may be found in patients suffering from a variety of severe diseases. The detection of EBL in peripheral blood has been shown to be associated with a poor prognosis. However, the clinical significance of peripheral erythroblastosis after hematopoietic stem cell transplantation (HSCT) has not been evaluated. We retrospectively analyzed the records of 161 patients who underwent HSCT at our hospital from June 1995 to October 2001. EBL at any level were detected in 94% of the patients. Forty-four and 11 patients experienced erythroblastosis exceeding 200 and 1,000/ul, respectively. The erythroblast count was higher in patients who died than in the survivors (geometric mean value 184 vs. 100/ul, P=0.01). High-level erythroblastosis ( >1,000/ul) within 180 days after HSCT was associated with an extremely poor prognosis (median survival 22.5 days). Among the possible confounding factors, the use of total body irradiation (RR 2.35, 95% CI 1.22 - 4.54, P=0.011) and the disease status before transplantation (RR 2.51, 95% CI 1.15 - 5.49, P=0.021) were independent significant factors for erythroblastosis after HSCT. As for post-transplant events, a high EBL concentration was frequently preceded by graft-vs.-host disease, thrombotic microangiopathy, hypoxia, and hematological relapse.

Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation.

Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by platelet aggregation and hemolytic anemia. In the setting of bone marrow transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate from acute graft-versus-host disease. We report a 32-year-old man who presented ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He suffered from treatment-resistant bloody diarrhea, and died of renal failure and Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries of arterioles and ischemic changes in the intestines and kidneys. Clinical and pathological characteristics of ischemic colitis due to BMT-associated TMA are described.

Rapid diagnosis of invasive pulmonary aspergillosis by quantitative polymerase chain reaction using bronchial lavage fluid.

Polymerase chain reaction (PCR) is a sensitive method for detection of Aspergillus DNA in bronchoalveolar lavage fluid, but it has not yet been able to distinguish infection from contamination. We have established a technique to quantify Aspergillus DNA using a real-time PCR method to resolve this problem, and we report herein a successful application of real-time PCR to diagnose invasive pulmonary aspergillosis by comparing the amount of Aspergillus DNA in bronchial lavage fluid from an affected area to that from an unaffected area. This novel tool will provide rapid, sensitive, and specific diagnosis of pulmonary aspergillosis.

Reduced-intensity bone marrow transplantation from an alternative unrelated donor for myelodysplastic syndrome of first-donor origin.

A male patient had a relapse of myelodysplastic syndrome (MDS) 2 years after BMT from a female matched unrelated donor. Conventional cytogenetics, FISH, and short-tandem repeat chimerism analysis proved a relapse of donor origin. He underwent reduced-intensity BMT after a conditioning with fludarabine and busulfan, since he had impaired renal, liver, and pulmonary functions. Chimerism analysis on day 28 after the second BMT showed mixed chimerism of the first and the second donors, which later turned to full second-donor chimerism on day 60. He developed grade II acute GVHD of the skin and cytomegalovirus reactivation, but both were improved with methylprednisolone and ganciclovir, respectively. He remains in complete remission 6 months after the second BMT. Reduced-intensity second BMT from an alternative donor appeared to be a tolerable treatment option for donor-derived leukemia/MDS after the first conventional transplantation.