Partially mismatched related donor bone marrow transplantation as salvage for patients with AML who failed autologous stem cell transplant.

Treatment options for patients who relapse are limited and the outcome is dismal. Between August 1993 and January 1999, 17 patients, median age 26 (4-44) years, underwent T cell depleted bone marrow transplant from partially mismatched related donors (PMRD), as a salvage for AML relapsing after an autograft. The median time from auto-transplant to relapse was 7 months (1.5-24) and the interval between transplants was 10 months (3-30). All patients had active leukemia at time of transplant. Donors were siblings (n = 8), parents (n = 2), daughters (n = 4) and others (n = 3), and 82% were > or = 2 major HLA antigen mismatched with the recipient. The conditioning therapy included total body irradiation in 14 patients and was busulfan-based in three. Graft-versus-host disease (GVHD) prophylaxis consisted of partial T cell depletion along with post-transplant immunosuppression. Median day to engraftment was 16 days (12-20). Acute GVHD was seen in six patients, and chronic GVHD in four of 13 surviving beyond 100 days. Ten patients died of non-relapse causes, at 1-588 (median 77) days. Two patients relapsed at 3 and 4 months. Five patients (29%) are surviving leukemia-free 42-84 months post transplant (median 68 months). A short interval between transplants was predictive of early relapse but not mortality. Age <18 and <2 organ toxicities were marginally predictive of better survival. We conclude that BMT from PMRD is a reasonable option for patients with refractory AML post autograft.

Candida glabrata and Candida krusei fungemia after high-risk allogeneic marrow transplantation: no adverse effect of low-dose fluconazole prophylaxis on incidence and outcome.

Candidemia is a serious complication in patients following allogeneic blood, marrow, and organ transplantation. Fourteen patients developed nosocomial fungemia among 204 allogeneic marrow transplants performed during 1997-1999. Incidence of hematogenous candidiasis was 6.8 per 100 allogeneic BMT. All 14 had an indwelling central venous catheter (CVC) and fluconazole (100-200 mg daily) was given prophylactically. In 11 (78.5%) neutropenic patients, duration between agranulocytosis and diagnosis of fungemia was (median, +/- s.d.) 10 +/- 8 days. Candida glabrata (53.3%) was the most common yeast species, followed by C. krusei (33.3%), and C. parapsilosis (13.3%). Candida albicans was conspicuously absent. Ten patients (71.4%) had primary transplant-related complication (>2 days) including hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) (n = 5), severe hemorrhagic cystitis (n = 3), and bacteremia (n = 2). Seven (50.0%) patients expired and in three (21.4%) deaths were attributed to fungemia. The impact of a primary transplant-related complication on short-term survival in this setting was not significant (P = 0.07) (HUS/TTP (P > 0.5); neutropenia (P > 0.5); GVHD (P = 0.35)). Removal of CVC did not alter outcome in our group (P > or = 0.5) although in patients with persistent fungemia (>72 h), and those with preceding bacteremia, mortality was significantly higher (P = 0.002). Conventional prognosticators of poor outcome did not adversely effect short-term survival in our transplant recipients with hematogenous candidiasis. The predominance of C. glabrata and C. krusei breakthrough infections was similar to what is seen with high-dose fluconazole (400 mg) prophylaxis, and no adverse effects of low-dose fluconazole in terms of increased incidence of non-susceptible Candida species was seen.

Cytogenetic correlation with disease status and treatment outcome in advanced stage leukemia post bone marrow transplantation: a Southwest Oncology Group study (SWOG-8612).

A retrospective cytogenetic study was performed to determine whether non-random chromosome aberrations were related to the outcome of marrow transplantation for advanced stage acute leukemia (AL) and chronic myelogenous leukemia (CML). The patients were registered on SWOG-8612, a randomized comparison of busulphan and cyclophosphamide (BU/CY) to fractionated total body irradiation and etoposide (FTBI/VP16) as preparatory regimens for allogeneic bone marrow transplant (BMT). Blume K. G., Kopecky K. J., Henslee-Downey J. P., Forman S. J., Stiff P. J., Le Maistre C. F. & Appelbaum F. R. (1987) Blood 81, 2187. Pretreatment cytogenetic studies were available for 90 (78%) of the 115 patients who proceeded to BMT. Patients were categorized by diagnosis (ALL/AML/CML), disease status ['good' risk = second complete remission (CR2) or CML-accelerated phase (AP); 'poor' risk = third complete remission (CR3), induction failure, florid relapse or CML-blast phase (BP)] and cytogenetic status (favorable = normal cytogenetics in AL or Philadelphia chromosome positive (Ph+) standard or variant translocation as the sole findings in CML; unfavorable = all other cytogenetic aberrations). Chromosomal aberrations observed in the unfavorable category included -7, t(9;22) in AL, t(8;21) in association with complex karyotypes, t(6;9), del(9q), t/del(11q), t(1;19), hypotetraploidy, and complex karyotypes (> 3 cytogenetic anomalies). Unfavorable cytogenetic status was significantly more frequent among patients with 'poor' risk clinical disease status (P < 0.0001). In multivariate analysis, disease-free survival (DFS) was significantly poorer for patients with unfavorable cytogenetic status (P = 0.002) but not significantly related to disease status (P = 0.43). These data indicate that certain secondary chromosome aberrations [+8,i(17q), duplication of Ph] should be reclassified as relatively favorable predictors of successful BMT in CML and, therefore, be separated from the unfavorable cytogenetic aberrations characteristic of drug resistant disease [-7, inv(3), complex karyotypes]. The limited number of patients precluded definitive assessment of the prognostic significance of specific cytogenetic aberrations for any single diagnosis. Nevertheless, these findings suggest that cytogenetic status may be an important and independent factor in predicting outcome following allogeneic bone marrow transplantation.

A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study.

Two novel preparatory regimens for conditioning of patients with leukemia for allogeneic bone marrow transplantation (BMT) from histocompatible sibling donors have been tested in a phase III trial under the auspices of the Southwest Oncology Group (SWOG 8612). These two regimens consisted either of fractionated total body irradiation and etoposide (FTBI/VP-16) or high-dose busulfan with cyclophosphamide (BU/CY). Only patients who had failed prior conventional management at least once were study eligible, ie, no patients with acute leukemia in first remission (CR) or in first chronic phase (CP) of chronic myelogenous leukemia (CML) participated. Patients were stratified according to the following risk criteria: "good-risk" patients were those who were in second CR of their acute leukemia or in accelerated phase (AP) of CML; "poor-risk" patients had further advanced stages of leukemia. During a 52-month period, 131 patients were registered of whom 122 (93%) were study eligible. Sixty-one eligible patients were randomized to the FTBI/VP-16 arm and 61 to the BU/CY regimen. Of these 122 patients, 114 (93%) proceeded to BMT according to protocol. Posttransplant immunosuppression to prevent graft-versus-host disease (GVHD) consisted of cyclosporine and prednisone (CSA/PSE). Neither overall survival nor disease-free survival (DFS) differed significantly between the two treatment groups (P = .89 and .69, respectively). Estimated DFS for "good-risk" patients who had been prepared with the FTBI/VP-16 regimen was 55% +/- 11%, as compared with patients treated with BU/CY whose DFS figure was 34% +/- 10% (P = .30). For "poor-risk" candidates, the DFS rates at 24 months were 17% +/- 6% (for FTBI/VP-16) and 24% +/- 8% (for BU/CY), respectively (P = .81). These figures do not differ significantly, especially in view of the fact that the "good-risk" patients prepared with the FTBI/VP-16 regimen were younger than those treated with BU/CY. Both regimens were well tolerated with no regimen-related deaths encountered during the 6-week period after BMT. This study also confirmed the efficacy of the CSA/PSE combination in the prevention of GVHD with 23 of 113 (20%) of BMT recipients developing moderate to severe acute GVHD. The leading cause for treatment failure was leukemic relapse (45 of the 114 BMT recipients suffered a recurrence of their leukemia), whereas 38 patients died without evidence of relapse. Thirty-one patients are alive and in continued CR after marrow transplantation; four are alive in relapse.(ABSTRACT TRUNCATED AT 400 WORDS)