High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.
Summary:Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study.
Summary:The purpose of the study was to determine the toxicities and effectiveness of a novel preparative regimen of busulfan (Bu) 14 mg/kg, etoposide 50 or 60 mg/kg, and cyclophosphamide (Cy) 120 mg/kg in non-Hodgkin's lymphoma (NHL) and to analyze results using doses based on different body weight parameters and the two different etoposide doses. Three hundred and eightytwo patients aged 16 to 72 underwent first autologous transplantation with mobilized peripheral blood progenitor cells between August 1992 and December 1998 at either of two transplant centers. Mucositis was the most common toxicity. Hepatic toxicity was the most common life-threatening toxicity; severe hepatic VOD occurred in 11 patients (2.9%). Ten patients (2.6%) died from treatment-related toxicity. The 3-year progressionfree survival (PFS) for the entire group was 46.9% (95% CI, 40.5-53.3%). Elevated LDH, resistance to chemotherapy, and intermediate/aggressive histology were significant adverse prognostic factors. For patients in sensitive first relapse PFS was 47.0% (95% CI, 37-57%). Neither etoposide dose nor body weight parameter utilized significantly affected outcome. In conclusion, the novel preparative regimen of Bu, etoposide and Cy results in a low incidence of treatment-related mortality and is effective in the treatment of patients with NHL. Bone Marrow Transplantation (2000) 25, 1243-1248. Keywords: autotransplantation; non-Hodgkin's lymphoma; busulfan High-dose chemotherapy followed by autologous transplantation of hematopoietic progenitor cells is curative in many patients with NHL who fail primary therapy. [1][2][3][4] The superiority of this approach over standard chemotherapy has been proven in patients with chemotherapy-sensitive, relapsed intermediate and high-grade NHL. 5 Autotransplantation is also commonly performed in patients with more advanced
G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.
More than 410,000 people participated in the National Marrow Donor Program (NMDP) as of October 1, 1991, and more than 850 volunteers had donated marrow. While the incidence of serious morbidity as a result of bone marrow donation is rare, the incidence of lesser complications and the long-term consequences of marrow donation are not known. To determine the incidence of donor complications and measure the recovery time of volunteer, unrelated marrow donors, we analyzed the results of surveys of the first 493 persons who donated marrow through the NMDP. The marrows were collected at 42 centers. The median age of the donors was 37.9 years (range 19.1 to 55.6 years). The median volume of marrow collected was 1,050 mL (range 180 to 2,983 mL). Autologous red blood cells were transfused to 89.8% (439) of donors but only 0.6% (3) of donors received allogeneic blood. Acute complications related to the collection procedure occurred in 5.9% of donors; but a serious complication, apnea during anesthesia, occurred in only one donor. When donors were questioned approximately 2 days following discharge from their hospitalization, most donors described symptoms related to the collection; 74.8% experienced tiredness, 67.8% experienced pain at the marrow collection site, and 51.6% of the donors experienced low back pain. Donors were surveyed repeatedly until they felt that they had recovered completely. Mean recovery time was 15.8 days; however, 42 (10%) donors felt that it took them > or = 30 days to recover fully. The duration of the marrow collection procedure and duration of anesthesia both positively correlated with donor pain and/or fatigue following the collection; but the duration of the collection procedure had the highest correlation with post-collection pain and fatigue. The volume of marrow collected per unit of donor weight was more weakly correlated with donor pain and/or fatigue than the anesthesia and collection times. When multivariate analysis was used to analyze the correlation between donor recovery time and these variables, only the duration of the collection was found to correlate significantly with donor recovery time (P = .001). This analysis demonstrates that marrow donation is well tolerated with few complications. To decrease further the incidence of donor discomfort and recovery time following donation, the duration of the collection procedure, and probably the duration of anesthesia, and the volume of marrow collected, should be kept to a minimum.
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