Retrospective analysis of cord blood transplantation on 62 adult patients with advanced hematological malignancies.

The Japan Cord Blood Network was established in 1999 and 8 institutions from the Kyushu Hematology Organization Study Group had performed cord blood transplantation (CBT) 67 times on 62 patients with advanced hematological malignancies from 1999 to 2004, which included acute and chronic leukemias in 34 patients, non-Hodgkin's lymphoma in 14, adult T-cell leukemia in 11 and others in 3 patients. The median age was 44 and disease status was no remission on 50 patients prior to CBT. Myeloablative conditioning regimens were used in 27 patients while 35 patients received non-myeloablatives. Engraftment could not be determined in 25 patients and the median survival time was 70 days. Thirteen patients were alive from 288 to 1277 days and 49 had been expired. The causes of death were the underlying disease in 19 patients, severe infection in 14 and graft-versus-host disease in 3 and miscellaneous in the remaining patients. This retrospective study shows that some patients with far-advanced hematological malignances could be successfully treated with CBT at the expense of many early deaths due to early relapse and severe infection. It is of importance that the appropriate indication for CBT should be discussed between transplant experts and patients and their families in each case.

Phase II study of cladribine (2-chlorodeoxyadenosine) in relapsed or refractory adult T-cell leukemia-lymphoma.

Adult T-cell leukemia-lymphoma (ATL) is a retrovirus-associated T-cell malignancy with an extremely poor prognosis; the median survival time of ATL patients with the acute or lymphoma type is less than 1 year with various combination chemotherapies. Cladribine (2-chlorodeoxyadenosine; 2-CdA), a purine analog resistant to degradation by adenosine deaminase, has shown definitive clinical activity against various lymphoid malignancies, including hairy cell leukemia, indolent lymphoma, and cutaneous T-cell lymphoma. An in vitro study showed the sensitivity of T-lymphoblastoid cell lines to cladribine, and a preceding Japanese phase I study of cladribine showed that 1 refractory patient with ATL achieved an objective response. To evaluate the therapeutic efficacy of cladribine in treating ATL, we conducted a multicenter phase II study. The plan was to administer cladribine to 30 ATL patients as 0.09 mg/kg per day by 7-day continuous intravenous infusion every 4 weeks for up to 3 courses. Before the planned interim analysis, 16 patients with relapsed or refractory ATL were enrolled, 15 of whom were eligible. Only 1 of the 15 eligible patients showed an objective response (overall response rate, 7%; 90% confidence interval, 0% to 28%), and 11 patients (73%) showed progressive disease, mostly during the first course of treatment. Because the upper limit of the 90% confidence interval of the overall response rate did not reach 30% in the interim analysis, the Independent Monitoring Committee advised us to discontinue patient enrollment. In conclusion, cladribine is not worthy of further investigation for the treatment of ATL.

Use of foscarnet for cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation from a related donor.

Foscarnet is an active agent against cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT), as well as ganciclovir. We investigated the usefulness of foscarnet in patients who underwent related allogeneic HSCT. Foscarnet was used in 320 patients with a median age of 45 years (range 15-72). The purpose of administration was CMV disease in 65, preemptive use in 248 and prophylaxis in 7. Totally, 194 patients had a history of prior ganciclovir treatment. The reason for foscarnet use was insufficient therapeutic effect of prior ganciclovir in 99, and adverse event including myelosuppression in 95. The response rate in symptom was 52% for the CMV disease patients. Antigenemia disappeared in 77% of the preemptive treatment and improved in 13% of the patients. No outbreak of CMV disease was recognized. The total effectiveness of therapeutic and preemptive use was significantly higher for patients without prior ganciclovir (91 vs. 76%, P = 0.001). Adverse events of grade 3 or higher were recognized in 24%, including electrolyte abnormalities in 11%, neutropenia in 8%, and thrombocytopenia in 8%. Renal damage was only observed in 3% of patients. Foscarnet was concluded to be a safe and effective anti-CMV agent and to be a suitable alternative to ganciclovir.