ABSTRACT

Purpose: The purpose of this research was to evaluate the feasibility of reduced-intensity unrelated cord-blood transplantation (RI-UCBT) in adult patients with advanced hematological diseases.Experimental Design: Thirty patients (median age, 58.5 years; range, 20 -70 years) with advanced hematological diseases underwent RI-UCBT at Toranomon Hospital between September 2002 and August 2003. Preparative regimen composed of fludarabine 25 mg/m 2 on days ؊7 to ؊3, melphalan 80 mg/m 2 on day ؊2, and 4 Gy total body irradiation on day ؊1. Graft-versus-host disease prophylaxis was composed of cyclosporin alone.Results: Twenty-six patients achieved primary neutrophil engraftment after a median of 17.5 days. Median infused total cell dose was 3.1 ؋ 10 7 /kg (range, 2.0 -4.3 ؋ 10 7 /kg). Two transplant-related mortalities occurred within 28 days of transplant, and another 2 patients displayed primary graft failure. Cumulative incidence of complete donor chimerism at day 60 was 93%. Grade II-IV acute graft-versus-host disease occurred in 27% of patients, with median onset 36 days. Primary disease recurred in 3 patients, and transplant-related mortality within 100 days was 27%. Estimated 1-year overall survival was 32.7%. Excluding 7 patients with documented infection, 19 patients displayed noninfectious fever before engraftment (median onset, day 9). Manifestations included high-grade fever, eruption, and diarrhea. The symptoms responded well to corticosteroid treatments in 7 of 13 treated patients.Conclusion: This study demonstrated the feasibility of RI-UCBT in adults.

In this small preliminary study, we found that donor age is the most important factor in predicting G-CSF-induced PBSC yields. Old age and low platelet counts before mobilization might be useful indicators for identifying poor mobilizers. Further validation of these findings in a larger number of donors are needed to establish whether these findings apply to other populations.

The online version of this article has a Supplementary Appendix. BackgroundPatients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse. Design and MethodsClinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy. ResultsAmong the 1,535 patients who were treated with chemotherapy alone, 1,015 relapsed. Half of them subsequently achieved a second complete remission. The overall survival was 30% at 3 years after relapse. Multivariate analysis showed that achievement of second complete remission, salvage allogeneic hematopoietic cell transplantation, and a relapse-free interval of 1 year or longer were independent prognostic factors. The outcome after allogeneic transplantation in second complete remission was comparable to that after transplantation in first complete remission. Patients with acute myeloid leukemia and cytogenetic risk factors other than inv(16) or t(8;21) had a significantly worse outcome when they did not undergo salvage transplantation even when they achieved second complete remission. ConclusionsWe found that both the achievement of second complete remission and the application of salvage transplantation were crucial for improving the prognosis of patients with acute myeloid leukemia in first relapse. Our results indicate that the optimal treatment strategy after first relapse may differ according to the cytogenetic risk.Key words: acute myeloid leukemia, allogeneic hematopoietic cell transplantation, first relapse, second remission, cytogenetic risk. 2010;95(11):1857-1864. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Kurosawa S, Yamaguchi T, Miyawaki S, Uchida N, Sakura T, Kanamori H, Usuki K, Yamashita T, Okoshi Y, Shibayama H, Nakamae H, Mawatari M, Hatanaka K, Sunami K, Shimoyama M, Fujishima N, Maeda Y, Miura I, Takaue Y, and Fukuda T. Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse. Haematologica Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse

Summary:From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre-emptive approach for CMV disease was evaluated in 77 adult patients who received allogeneic hematopoietic stem cell transplantation at the National Cancer Center Hospital. A CMV antigenemia assay was performed at least once a week after engraftment. High-level antigenemia was defined as a positive result with 10 or more positive cells per 50 000 cells and low-level antigenemia was defined as less than 10 positive cells. Among the 74 patients with initial engraftment, 51 developed positive antigenemia. Transplantation from alternative donors and the development of grade II-IV GVHD were independent risk factors for positive antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients in a risk-adapted manner. None of the nine low-risk patients with low-level antigenemia as their initial positive result developed high-level antigenemia even though ganciclovir was withheld. Only one patient developed early CMV disease (hepatitis) during the study period. CMV antigenemia resolved in all but two cases, in whom ganciclovir was replaced with foscarnet. In eight patients, however, the neutrophil count decreased to 0.5 × 10 9 /l or less after starting ganciclovir, including three with documented infections and two with subsequent secondary graft failure. The total amount of ganciclovir and possibly the duration of high-dose ganciclovir might affect the incidence of neutropenia. We concluded that antigenemia-guided pre-emptive therapy with a decreased dose of ganciclovir and response-oriented dose adjustment might be appropriate to decrease the toxicity of ganciclovir without increasing the risk of CMV disease. Bone Marrow Transplantation (2001) 27, 437-444.

Summary:To evaluate the efficacy of long-term administration of acyclovir as prophylaxis against varicella-zoster virus (VZV) reactivation, we analyzed the medical records of 86 consecutive adult patients who obtained engraftment after allogeneic hematopoietic stem cell transplantation from January 1996 to March 2000. We started longterm low-dose (400 mg/day) oral administration of acyclovir in June 1999, and this was continued until the end of immunosuppressive therapy after transplantation. There was no breakthrough reactivation of VZV in patients receiving acyclovir. Five patients who were receiving cyclosporine or prednisolone developed VZV reactivation after discontinuing acyclovir. With this prophylaxis, the cumulative incidence of VZV reactivation at 1 year after transplantation decreased from 33% to 10% (P = 0.025). On multivariate analysis, the use of long-term acyclovir was identified as a significant independent parameter for the development of VZV reactivation. These findings suggest the efficacy of longterm prophylaxis with low-dose acyclovir. Resumption of acyclovir upon restarting immunosuppressive therapy might be important for the further prevention of VZV reactivation. The benefit of long-term low-dose acyclovir should be confirmed prospectively. Bone Marrow Transplantation (2001) 28, 689-692.

While the results suggested an association between the degree of hyperglycemia during neutropenia and an increased risk of posttransplant complications and NRM, the possibility that intensive glucose control improves the outcome after HSCT can only be confirmed in a prospective randomized trial.

Summary. The feasibility of allogeneic haematopoietic stemcell transplantation (allo-HSCT) in 11 patients with adult T-cell leukaemia/lymphoma (ATL) (6 acute, 4 lymphoma, 1 chronic type) was evaluated. The preparative regimens (9 conventional, 2 reduced-intensity) were tolerable. Five patients developed acute graft-versus-host disease (GVHD), and three, extensive chronic GVHD. All 10 patients who survived > 30 d achieved complete remission. Estimated 1-year overall and disease-free survival rates were 53 ± 30% and 45 ± 29% respectively. Four patients remain alive and disease-free at a median follow-up of 25 months. The others died of transplantation-related complications. This pilot study suggests that allo-HSCT in ATL should be evaluated further.