Summary:Between 1985 and 1998, 161 patients with primary acute myeloid leukemia (AML) received T-replete bone marrow transplantation (BMT) from unrelated donors in Seattle. Median age was 30 (range 1-55) years. Conditioning for BMT consisted of cyclophosphamide and total body irradiation in 154 (96%) cases and graftversus-host disease prophylaxis was the standard methotrexate and cyclosporine combination in 134 (83%) cases. Median post-transplant follow-up was 2.9 years. Leukemia-free survival (LFS) at 5 years was 50 ؎ 12% for transplants during first complete remission (n = 16), 28 ؎ 8% during second CR (n = 40), 27 ؎ 17% during subsequent CR (n = 8), 7 ؎ 3% during relapse (n = 81) and 19 ؎ 10% during primary induction failure (n = 16). The cumulative incidences of relapse were 19%, 23%, 25%, 44% and 63%, for the five groups, respectively. Transplantation during remission, a marrow cell dose above 3.5 ؋ 10 8 /kg, and cytomegalovirus seronegative status before BMT in both patient and donor were favorable prognostic factors. Adults in any CR who received a marrow cell dose above 3.5 ؋ 10 8 /mg had a LFS of 54 ؎ 9% at 5 years. These data extend our previous findings on the association between a high marrow cell dose and improved survival and support the use of unrelated donor BMT for treatment of patients with high risk AML when a family match is not available. Bone Marrow Transplantation (2000) 26, 397-404.

Therapeutic, II.(Figure is included in full-text article.).

Four patients with refractory malignant B cell lymphomas were treated with continuous intravenous (IV) infusions of murine monoclonal antibody (MoAb) 1F5 (anti-CD20) over five to ten days. Dose-dependent levels of free serum 1F5 were detected in all patients. Two patients had circulating tumor cells and in both cases 90% of malignant cells were eliminated from the blood stream within four hours of initiation of serotherapy. Antigenic modulation did not occur, and sustained reduction of circulating tumor cells was observed throughout the duration of the infusions. Serial bone marrow aspirations and lymph node biopsies were examined by immunoperoxidase and immunofluorescence techniques to ascertain MoAb penetration into extravascular sites. High doses (100 to 800 mg/m2/d and high serum 1F5 levels (13 to 190 micrograms/mL) were required to coat tumor cells in these compartments in contrast to the low doses that were adequate for depletion of circulating cells. Clinical response appeared to correlate with dose of MoAb administered with progressive disease (52 mg), stable disease (104 mg), minor response (1,032 mg), and partial response (2,380 mg) observed in consecutive patients. The patient treated with the highest 1F5 dose achieved a 90% reduction in evaluable lymph node disease, but the duration of this remission was brief (six weeks). This study demonstrates that high doses of 1F5 can be administered to patients with negligible toxicity by continuous infusion and that clinical responses can be obtained in patients given greater than 1 g of unmodified antibody over a ten-day period.

This HIFU device exhibited an AE profile similar to that of sham treatment. There were no significant changes from baseline in laboratory values, including lipid levels.

These data indicate that approximately 60% of patients transplanted early after failure of initial therapy for malignant lymphoma are projected to be disease-free more than 2 years after treatment with fractionated TBI, etoposide, and Cy and infusion of autologous hematopoietic stem cells. The transplant-related mortality rate is low and relapse is the main cause of treatment failure in patients with less advanced disease. For patients with more advanced disease, the K-M estimates of both transplant-related deaths (25%) and relapse (53%) remain major problems.

© Ferrata Storti Foundation P.S. Martin et al. 500haematologica | 2016; 101(4) nificant impact on transplant outcomes in the RIC setting. However, relatively few studies have reported on productrelated outcome data in RIC transplants. These studies have primarily focused on CD34 + cell dose, most reporting that higher CD34 + cell doses are associated with more rapid engraftment with a variable effect on the incidence of graft-versus-host disease (GVHD) and survival outcomes. [1][2][3][4][5] Gomez-Almaguer and colleagues reported on 138 recipients of RIC hematopoietic stem cell transplants, showing that higher CD34 + doses correlated with improved overall survival. 6 A CIBMTR registry analysis of 1054 RIC hematopoietic stem cell transplant recipients found that lower CD34 + doses correlated with increased transplant-related mortality and decreased overall survival. 7 In contrast, Remberger and colleagues reported that higher CD34 + doses were actually associated with higher relapse rates and lower overall survival. 8 Relative to CD34 + cell dose, total nucleated cell (TNC) dose has been less frequently studied. However, in the limited number of studies that have examined TNC, a trend toward improved survival outcomes with higher TNC dose, independently of CD34 + dose, has been found. 9,10 The current study examines the impact of both TNC and CD34 + cell dose on major transplant outcomes in a cohort of 705 consecutive patients undergoing RIC allogeneic peripheral blood hematopoietic stem cell transplantation. MethodsWe analyzed data from 705 consecutive patients with hematologic malignancies undergoing RIC utilizing granulocyte colonystimulating factor-mobilized donor peripheral blood mononuclear cells as a graft source. Patients who underwent either in vivo T-cell depletion with antithymocyte globulin or ex-vivo T-cell depletion were excluded from the study. All patients had at least 3 years of follow-up after their transplant. All patients provided consent to the use of protected health data for research, as approved by a common institutional review board of the Dana-Farber/Harvard Cancer Center. Definitions and end-pointsNeutrophil engraftment was defined as the first day of an absolute neutrophil count >500/mL on three consecutive measurements. Platelet recovery was defined as the first day of two consecutive measurements of >20,000/mL (unsupported). Acute and chronic GVHD were graded by consensus grading criteria and their cumulative incidence was calculated through day +200 after hematopoietic stem cell transplantation. Chronic GVHD was defined clinically by treating physicians utilizing standard criteria ultimately supplanted by NIH Consensus Conference recommendations.11 Relapse was defined as disease recurrence documented by morphological, histological or radiographic means. Treatmentrelated mortality was defined as death while in continuous remission. Progression-free survival was defined as the time from transplantation to relapse or death from any cause, and overall survival was defined as ...

Allo BMT following a high-dose CBV regimen resulted in long-term disease-free survival in 17% of patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. A high incidence of transplant-related complications, especially fatal idiopathic pneumonia syndrome (IPS) and a high relapse rate limited success. Morbidity and mortality associated with carmustine 600 mg/m2 were high and were not associated with a decrease in relapse. The number of patients in this study eligible for either allo or auto BMT was limited and precluded meaningful analysis of relative effectiveness.

These results suggest that ABMT may produce long-term leukemia-free survival in approximately one third of patients with AML in REL1 or in REM2. There is no apparent clinical advantage in attempting to obtain second remissions in relapsed patients before ABMT if marrow has been cryopreserved during REM1. Although a strategy of transplantation in REL1 has advantages for the patient, such an approach involves the storage of marrow, which may not be used, and is impractical without the coordinated support of the treating physician, the patient, and the marrow transplant center.