Cryopreservation of stem cells after collection from peripheral blood or bone marrow for autologous transplantation necessitates protection with dimethyl sulfoxide (DMSO). Unfortunately, DMSO, when infused with the thawed cell suspension, may induce serious complications and side effects. To assess whether depletion of DMSO before autografting affects safety and efficacy, 56 consenting consecutive patients treated with high-dose chemotherapy and autologous blood stem cell transplantation were assigned to obtain either an untreated or DMSO-depleted autograft. On the day of transplantation, the cryopreserved cells were thawed and infused to the patient either immediately or after washing 3 times in normal saline supplemented with 6% anticoagulant citrate dextrose solution. Cell count with viability, clonogenic assay, and phenotyping were performed before and after thawing and after washing. Hematologic recovery, side effects, and complications were recorded. The in vitro and clinical data on 56 patients show that the depletion of DMSO in vitro before autografting does not induce a significant loss of cell number, viability, colony-forming unit-granulocyte-macrophage activity, or number of CD34(+) cells. Furthermore, it leads to a safe and sustained engraftment. The complications and side effects, as recorded by continuous monitoring, were substantially less; however, the procedure takes 3 to 4 hours of laboratory work per patient.

1. The diabetic neuropathic foot exhibits excess arteriovenous anastomotic shunt flow due to a reduced sympathetic vasoconstrictor tone. Local axon reflexes (mediating postural vasoconstriction, for example) are preserved even in severe diabetic neuropathy. This excess shunt flow and its local neurogenic control may be important in the development of complications of the neuropathic limb. 2. The response of arteriovenous anastomoses to local heating was assessed in 13 diabetic patients with neuropathy (12 insulin-dependent), 10 diabetic control patients (seven insulin-dependent) and 10 normal control subjects. The aim was to study the local reflex control of arteriovenous flow when central sympathetic tone had been largely removed. 3. The change in skin blood flow on local heating to 44 degrees C was measured by using a laser Doppler flowmeter in standard environmental conditions with the foot at heart level. Two sites were assessed: (i) the plantar surface of the great toe (a site in which skin blood flow is dominated by arteriovenous shunt flow) and (ii) the dorsum of the foot (a site without anastomotic flow). 4. It was found that when heat was applied to the plantar surface of the great toe in the diabetic patients with neuropathy a paradoxical decrease in flow through arteriovenous anastomoses occurred, flow declining to 65% (P less than 0.05) of its resting value. This could be compared with an increase in flow over the same time period of 262% and 228% (P less than 0.01) in diabetic control patients and normal subjects, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary:Patients (n = 69) with multiple myeloma undergoing peripheral blood stem cell collection (PBSC) were treated with cyclophosphamide and a combination of recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) and recombinant methionyl human stem cell factor (r-metHuSCF, ancestim). The objectives of this study were to determine: (1) The proportion of patients reaching a target yield of у5 ؋ 10 6 CD34 + cells/kg in one or two successive large-volume (20 liter) leukapheresis procedures; (2) the optimal collection time for leukapheresis; (3) mobilization kinetics of CD34 + subsets in response to G-CSF/SCF. All patients were mobilized with cyclophosphamide (2.5 g/m 2 ) on day 0 followed by filgrastim (10 g/kg ) plus ancestim (20 g/kg) commencing day 1 and continuing to day 11 or 12. Of the 65 evaluable patients, 57 were considered not heavily pretreated and 96.5% and early progenitors and the ability to predictably schedule leukapheresis.

Summary:Recent reports from large amyloidosis referral centers suggest that primary systemic AL amyloidosis patients treated with high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) survive longer than historical controls treated with less intensive chemotherapy, despite high transplant-related mortality (TRM) rates of 410%. A retrospective review was conducted to determine if the outcome of ASCT for AL amyloidosis at our institution was similar to that reported at major amyloidosis referral centers. Over a 7 year period, we treated a total of 15 AL amyloidosis patients with ASCT, including four with poor prognosis cardiac or multisystem involvement. No TRM was observed. Overall, 10 patients (67%) achieved a complete hematological response and four patients (27%) achieved a complete organ response. The 4-year event-free and overall survival rates were 60% (95% CI 32-89%) and 75% (95% CI 50-100%), respectively. One patient, who presented with cardiac failure and multiorgan involvement with colonic bleeding currently remains in complete remission 62 months post-ASCT. In conclusion, ASCT for primary AL amyloidosis can safely be performed at experienced transplant centers that are not associated with major amyloidosis referral centers, and is feasible for patients who have multisystem involvement, particularly for motivated patients with good performance status. In primary systemic AL amyloidosis, amyloid fibrils derived from monoclonal immunoglobulin light chains are produced by an underlying clonal plasma cell dyscrasia.These amyloid fibrils accumulate in vital organs, leading to progressive organ dysfunction, physical debility and death. The median survival of untreated patients is 10-14 months, while that of patients with cardiomyopathy and congestive heart failure is generally less than 6 months.1,2 Conventional chemotherapy with melphalan and prednisone produces response rates between 20 and 30%, median survival times of 12-18 months, and 5-year survival rates of 15%. 3-5High-dose melphalan (HDM) with autologous peripheral stem cell transplantation (ASCT) is a promising therapeutic option which initially demonstrated hematological response rates of 62% and organ response rates as high as 44% in small series.6,7 Unfortunately, reported transplant-related mortality (TRM) rates are high, between 15 and 43%.7-10 Therefore, prognostic variables were analyzed in an attempt to better select patients and reduce TRM. Patients with poor performance status, symptomatic cardiac involvement, or involvement of greater than two organs tended to have increased TRM and were considered poor candidates for ASCT.6-12 Although HDM/ASCT seems to produce higher response and survival rates than conventional chemotherapy, criteria for selecting patients for ASCT are still not firmly established. [12][13][14][15] Owing to the high TRM of HDM/ASCT for primary systemic AL amyloidosis, it may be possible that the results of this form of aggressive therapy are better when administered at tertiary referral centers that...