Safe early discharge for patients undergoing high dose chemotherapy with or without stem cell transplantation: a prospective analysis of clinical variables predictive for complications after treatment.

AIM: To identify which patient groups can be safely discharged early after high dose chemotherapy. BACKGROUND: Until recently, the standard of care for patients with haematological malignancies who have been treated with high dose chemotherapy has been to hospitalise them until neutrophil recovery and clinical improvement. Over the past years, a more liberal approach has resulted in a tendency to discharge patients earlier. However, currently it is unclear which clinical variables are important and which patient groups are most suitable to be discharged early. DESIGN: Prospective cohort study. METHODS: The study group of 55 patients underwent 82 admission periods for a total of 2269 patient days, which could be classified into four categories: induction treatment, consolidation treatment and autologous or allogeneic stem cell transplantation. Different clinical variables potentially interfering with early discharge were subsequently analysed for their association with each treatment group. RESULTS: The median duration of admission was 27 days. The incidence of fever (82.9%) and use of intravenous antibiotics (79.3%) was high in all treatment groups. The only statistically significant differences between groups were found for performance status and mucositis. In the patient group undergoing consolidation chemotherapy for acute myeloid leukaemia, the performance status was better and mucositis was less severe. The decline in performance status and the severity of mucositis were as expected most obvious 10-14 days after the start of chemotherapy. CONCLUSION: Patients undergoing consolidation chemotherapy appear to be the most suitable candidates for early discharge, especially in the first-week postchemotherapy treatment. Early discharge can also be considered in patients with a good performance status in the autologous stem cell transplantation group, directly after transplantation. RELEVANCE TO CLINICAL PRACTICE: An important factor in developing an early discharge programme is a good infrastructure, both at home and in the hospital.

Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers.

PURPOSE: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. METHODS AND MATERIALS: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia and non-Hodgkin's lymphoma. The TBI regimens were normalized by using the biological effective dose (BED) concept. The BED values were divided into three dose groups. Study end points were relapse incidence (RI), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). Multivariate analysis was performed, stratified by disease. RESULTS: In the highest TBI dose group, RI was significantly lower and NRM was higher vs. the lower dose groups. However, a significant influence on RFS and OS was not found. Relapses in the eye region were found only after shielding to very low doses. Age was of significant influence on OS, RFS, and NRM in favor of younger patients. The NRM of patients older than 40 years significantly increased, and OS decreased. There was no influence of age on RI. Men had better OS and RFS and lower NRM. Type of transplantation significantly influenced RI and NRM for patients with acute leukemia and non-Hodgkin's lymphoma. There was no influence on RFS and OS. CONCLUSIONS: Both RI and NRM were significantly influenced by the size of the BED of single-dose or two-fraction TBI regimens; OS and RFS were not. Age was of highly significant influence on NRM, but there was no influence of age on RI. Hyperfractionated TBI with a high BED might be useful, assuming NRM can be reduced.

Prognostic index for adult patients with acute myeloid leukemia in first relapse.

PURPOSE: The treatment of acute myeloid leukemia (AML) in first relapse is associated with unsatisfactory rates of complete responses that usually are short lived. Therefore, a clinically useful prognostic index can facilitate therapeutic decision making and evaluation of investigational treatment strategies at relapse of AML. PATIENTS AND METHODS: A prognostic score is presented based on the multivariate analysis of 667 AML patients in first relapse among 1,540 newly diagnosed non-M3 AML patients (age 15 to 60 years) entered onto three successive Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research Collaborative Group trials. RESULTS: Four clinically relevant parameters are included in this index (ie, length of relapse-free interval after first complete remission, cytogenetics at diagnosis, age at relapse, and whether previous stem-cell transplantation was performed). Using this stratification system, three risk groups were defined: a favorable prognostic group A (overall survival [OS] of 70% at 1 year and 46% at 5 years), an intermediate-risk group B (OS of 49% at 1 year and 18% at 5 years), and a poor-risk group C (OS of 16% at 1 year and 4% at 5 years). CONCLUSION: The prognostic index estimates the outcome of AML patients in first relapse using four commonly applied clinical parameters and might identify patients who are candidates for salvage and investigational therapy.

Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial.

The question as to whether autologous stem cell transplantation (SCT) after consolidation chemotherapy improves the probability of survival of patients with acute myeloid leukaemia (AML) in first remission has not been settled. Here, we present the results of a phase III study conducted in newly diagnosed adult AML patients aged <60 years. Patients who had reached a complete remission (CR) after two courses of induction chemotherapy and who were not eligible for a human leucocyte antigen-matched sibling SCT (n = 130), were randomized after a third consolidation cycle of chemotherapy between high-dose cytotoxic treatment and autologous bone marrow transplantation or no further treatment. No significant differences in disease-free survival and overall survival were observed between the two treatment arms. A slightly better overall survival in the no further treatment arm was because of fewer deaths in the first CR and a significantly better overall survival after the first relapse. The results are discussed in relation to the generic problems of applying autologous transplantation and in the perspective of the limited statistical power of this and other previously published studies.

Granulocyte colony-stimulating factor mobilized whole blood containing over 0.3 x 106/kg CD34+ cells is a sufficient graft in autologous transplantation for relapsed non-Hodgkin's lymphoma.

The feasibility of unprocessed, granulocyte colony-stimulating factor (G-CSF)-mobilized whole blood (WB) as an alternative stem cell source for autologous stem cell transplantation was studied. Forty-seven relapsed non-Hodgkin's lymphoma (NHL) patients entered the study. After two or three ifosfamide, methotrexate and etoposide (IMVP) courses, 1 l of G-CSF-mobilized WB was collected and stored refrigerated for 72 h. Meanwhile, BAM conditioning was given: BCNU (carmustine) 300 mg/m(2), high-dose cytarabine 6000 mg/m(2) and melphalan 140 mg/m(2). Toxicity, haematological recovery and survival were assessed and compared with peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) reference groups. High-dose G-CSF (2 x 12 microg/kg/d) gave the best mobilization results. Haematological recovery was related to the WB CD34+ content. A CD34+ threshold of >or= 0.3 10(6)/kg, obtained in 90% of patients using high-dose G-CSF, correlated with adequate recovery: absolute neutrophil count (ANC) > 0.5 x 10(9)/l: median 12 d (range 9-19). Platelet recovery > 20 and > 50 x 10(9)/l was 19 (11-59) and 30 d (14 not reached) respectively. Overall survival of patients < 60 years was 57% at 4 years and event-free survival was 32%. Survival was comparable with PBSCT and BMT after BEAM (BCNU, etoposide, cytarabine, melphalan). Remarkably, haematological recovery after BAM + WB was rapid and comparable (ANC) or slightly prolonged (platelets) in comparison with BEAM + PBSCT, despite a 10-20 times lower CD34+ cell dose in the WB graft. In conclusion, transplantation of WB containing >or= 0.3 x 10(6)/kg CD34+ cells after BAM conditioning is a safe procedure, and offers a fully equivalent and less costly alternative for PBSC.