High dose chemotherapy followed by autologous haemopoietic stem cell transplant in multiple myeloma.

BACKGROUND: High dose chemotherapy followed by autologous stem cell transplant is currently used for the treatment of patients with advanced multiple myeloma. However, there are no reports of the results of this treatment modality in Indian patients. METHODS: Fifty patients with advanced multiple myeloma underwent treatment with high dose melphalan followed by autologous stem cell transplant (bone marrow: 7; peripheral blood stem cells: 43). The patients' ages ranged from 26 to 65 years (median: 52 years) and 35 were men. All patients had received chemotherapy initially with a mean of 9.4 cycles (range: 1-36). Thirty patients had evidence of chemosensitive disease at the time of transplant. The mean interval from diagnosis to transplant was 17.5 months (range: 3-129 months) and the median number of mononuclear cells infused was 4.86 x 10(8) per kg (range: 2-10.48). RESULTS: Post-transplant, 43 of 50 patients engrafted. The median number of days to engraftment (absolute neutrophil count > 500/cmm) was 12 (range: 9-24) and to achieve platelet transfusion independence (> 20,000/cmm) was 13 (range: 8-36). Seven patients died prior to engraftment. Grade III-IV oral mucositis was the major non-haematological toxicity. Excluding the 4 patients who had complete response prior to the transplant and continued in the same status post-transplant, 31/46 patients (67%) responded; complete response was achieved in 25 (54%) and partial response in 6 (13%). Patients with chemosensitive disease had higher rates of complete response; 20 of 26 patients with partial response at transplant achieved complete response compared to 5 of 20 patients with persistent/refractory disease (p < 0.01). Currently, 34 of 50 (68%) patients are alive, 17 (34%) disease-free, 6 with disease are on salvage therapy, 11 (22%) with positive monoclonal protein but asymptomatic are under observation. Nine (18%) patients have died; 8 due to progressive disease and 1 of an unrelated cause. The median follow up for the entire group is 26 months (range: 1-144 months). The Kaplan-Meier probability of overall and progression-free survival for the whole group at 30 months is 62% +/- 8.11% (SE) and 42% +/- 9.54% (SE), respectively. A haemoglobin level < or = 10 g/dl (p < 0.003) affected the survival adversely. Chemosensitive disease (p < 0.008) at transplant and complete response post-transplant (p < 0.0001) were associated with significantly longer survival. CONCLUSION: High dose melphalan followed by autologous stem cell transplantation is an effective treatment for patients with advanced multiple myeloma and achievement of complete response is associated with improved survival.

Multiple organ dysfunction syndrome.

The simultaneous dysfunction of several organs represents a challenging task for the intensivist. Systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) are expressions of an inappropriate generalized inflammatory response of the host to a variety of infectious or non-infectious stimuli. In recent years, MODS is being encountered frequently in critically ill patients due to several causes. Experimental and clinical evidence suggests that the gut, endothelium and immune system interact to produce altered metabolic and cardiorespiratory patterns. It is thus possible that a target-oriented approach, including correction of intestinal hypoperfusion, supply of specific nutrients and downregulation of the inflammatory cascade, can act as either a preventive measure for subjects as risk or as the treatment for patients with full-blown MODS.

Brain death and organ donation.

Brain death is the irreversible cessation of all brain functions. Brainstem death is the 'physiological core' of brain death. The Indian Parliament has given legal recognition to brain death though it applies only in the context of performance of organ transplantation. Brain death is diagnosed if there is irreversible loss of consciousness, absence of brainstem reflexes and apnoea. Care and diligence in the application of the criteria for brain death provide important safeguards for Individual patients and the community in general. These criteria also allow death to be diagnosed with certainty prior to the occurrence of circulatory arrest. Solid organ transplantation has become possible through the diagnosis of brain death but is not the primary consideration; the management of a potential organ donor, who is brain dead, is also vital. If optimal preservation of organs for transplantation is to be achieved the clinician needs to understand the pathophysiology and consequences of changes occurring in various organs after brain death and active management is required to reverse or control these changes. Discussions about organ donation with relatives of brain deed patients are never easy. These should always be frank and sympathetic. It has been suggested that those whose interests lie in transplantation must bear the responsibility of educating the general public. This will help intensivists who expose themselves knowingly to the unpleasant aspects of organ donation.