ALBERT

Description: Myeloablative transplant has been investigated in poor prognosis indolent lymphoma; although recurrence rate is low it is associated with high mortality; the use of non-myeloablative conditioning regimens could reduce TRM maintaining the GVH effect. Up to February 2004, 40 patients with indolent NHL(87% Folicular lymphoma(FL) 5% a lymphocytic well differenciate lymphoma (WDLL) 5% Waldenström Macroglobulinemia(WM) and 3% a Marginal Lymphoma(MZL) have been registered in two prospective multicenter trials;Conditioning regimen consisted of Fludarabine 150 mg and Melphalan 70–140 mg. GVHD prophylaxis consisted of CSA plus short-course MTX. All patients received filgrastim-stimulated peripheral blood stem cells from a HLA related identical donor.Median age at transplant was 50 years (34–67) and 15(40%) had received a previous autologous transplant. At transplant, 5 patients (13%) were in CR1 (after several lines of chemotherapy), 9 (22%) in 〉CR1, 16 (40%) in PR, 1(2%) had stable disease (after 3 chemotherapy lines) and 9(23%) progressive disease. All patients engrafted. Acute GVHD developed in 22 patients (55%) (18 patients grade II–IV). Chronic GVHD developed in 22 out of 27 patients at risk (81%), being extensive in 13; Disease was evaluated at day +100 and at that moment 22 patients(58%) were in CR, 3 (8%) in PR, two (5%) had stable disease and 11 patients (27%) have died. With a median follow up of 30 months (range: 10–56 months), 24 patients (60%) are alive disease free, 16 (39%) have died, 14 of them (35%) due to transplant toxicity and 2 patients (5%) due to progression. Overall Survival (OS) and Event Free Survival (EFS) are 60 and 58 % respectively. Analysing variables which influence on OS and EFS, patients ≥55 years have a OS significantly shorter than patients 〈 55 years old (22% vs 66%; p:0,01). Moreover, patients who develop chronic GVHD have an OS and EFS significantly better than those which do not develop it (OS: 89,7 vs 57%; p=0,02 (HR: 9,3-IC95% (2,08–41,5); EFS: 89 vs 42%; p=0,002 (HR: 11,08-IC95% (2,49–49,28)). In conclusion, our results demonstrates the efficacy of non-myeloablative transplant in indolent NHL with a very low relapse rate, indicating the important role of chronic GVHD in the control of the disease; however, mortality rate is still high, mainly in patients ≥55 years

Description: Current protocols for cryopreservation prior to autologous peripheral blood stem cell transplantation (APBSCT) are usually based on 10% DMSO as an intracellular cryoprotectant with or without HES as extracellular cryoprotectant. The toxic effects related to DMSO infusion are usually dose-related and mild but can be severe including blood pressure alterations and arrhythmia. HES is a relatively nontoxic drug but it is related with pruritus and nephrotoxicity. Cryopreservation is usually performed by controlled-rate methods, followed by storage in liquid nitrogen. These procedures are time consuming and require expensive devices. Ten years ago we described a simplified cryopreservation technique at −80°C without rate-controlled freezing followed by storage in the same mechanical freezer and with 5% or 10% DMSO concentrations as the sole cryoprotectant (without HES). We report now a long-term evaluation of our experience along 12 years. Between July 1993 and September 2004, we performed 297 consecutive APBSCT for patients with solid and hematologic malignancies. Grafts were cryopreserved using 10% (n=47) and 5% (n=250) DMSO. Biological data of grafts, hematologic recovery and clinical data of cases were recorded. Special monitoring of infusion-related toxicity (IRT) was done. The median storage times were 31 and 28 days for 5% and 10% DMSO groups (p=NS). Post-thaw nucleated cell viability was 85% and 85.5% for 5% and 10% DMSO groups (p=NS). Patients included in the 5% DMSO group received a higher number of mononuclear and CD34+ cells. Criopreservation time did not significantly influence viability or hematopoietic recovery inside the criopreservation period (203 days or less). Significant IRT was higher in the 10% DMSO group: 21.3% versus only 7.2% in the 5% DMSO group (p=0.002), including hypertension, bradycardia, tachycardia, chest tightness and abdominal pain. Mild IRT was more than double in the 10% DMSO group: 10.6% versus 4% in the 5% DMSO group (p=0.07). No severe toxicities or death-related to infusion have been noted. All patients showed a safe and sustained engraftment. Median time to 500 and 1000 neutrophil/microL was the same in the two groups (11 days). Median time to 20 and 50 platelets/L was higher in the 5% vs 10% DMSO group: 12 vs 11 (p=0.03) and 17 vs 13 (p60%. G-CSF administration from day +5 postransplant was also related with a faster neutrophil recovery. Transplantation-related mortality was 2.8% and 2.1% respectively for 5% and 10% DMSO groups (p=NS). Long-term clinical evaluation of autologous transplantation with blood stem cells cryopreserved with 5% or 10% DMSO at −80°C without rate-controlled freezing shows that these are feasible procedures with engraftment, hematologic reconstitution and outcomes comparable to standard rate-controlled freezing protocols. Significant and mild IRT were lower in the 5% DMSO group compared with the 10% DMSO group.