Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).     

Management Strategies for Relapsed Multiple Myeloma

Multiple myeloma is the second most common hematologic malignancy after non-Hodgkin lymphoma. Numerous treatments for this disease are available, but despite high overall response rates, relapse occurs in almost all patients, and survival has typically been no more than 5 years. Treatment options for relapsed patients include pulsed dexamethasone; cyclophosphamide-based therapy; doxorubicin-based regimens; melphalan and prednisone; thalidomide with or without dexamethasone; bortezomib; and high-dose chemotherapy supported by autologous or allogeneic stem cell transplantation. Relapsed disease is more difficult to treat, and patients characteristically become resistant to therapy. As a result of the numerous potential complications of multiple myeloma, including fatigue, bone pain, renal dysfunction, increased susceptibility to infection, and spinal cord compression, quality of life has a significant role in the choice of therapy. New strategies in the treatment of relapsed disease are focusing on therapy that is targeted to various cell-signaling pathways and microenvironmental interactions involved in the pathogenesis of multiple myeloma. As they become available, these strategies are showing promise in the treatment of both relapsed and refractory disease, the most recent being the potent thalidomide analog lenalidomide. Research efforts are also concentrated on improving front-line therapy to reduce the rate of relapse so that, ultimately, survival may be extended and patient outcome improved.     

Acute lower respiratory infections: a major cause of death in children in Bangladesh

The importance of acute lower respiratory infections (ALRI) as a cause of death in children was estimated using systematically collected demographic data on the population of the Teknaf area of southern Bangladesh. Of 1349 children aged 1-59 months who died between 1 January 1982 and 31 December 1985, ALRI was diagnosed by verbal autopsy in 390 (29%) and was the leading cause of death. ALRI mortality rates were highest in the youngest age groups (136/1000 for those less than or equal to 5 months) and decreased in older children (16/1000 for those 3-4 years old). Half of all fatal ALRI cases occurred in children less than 6 months old. In older children, ALRI-associated deaths tended to occur during the months October to January, while deaths in infants tended to follow the seasonal birth pattern. Significant predisposing factors for fatal ALRI were malnutrition and measles, detected, respectively, in 18% and 8% of children who died from ALRI. This study emphasizes the importance of ALRI as a major cause of death in developing countries and suggests that interventions to reduce childhood mortality are needed and should be targeted to specific age groups at risk.