HPCs can be cryopreserved at -80 degrees C with 5-percent DMSO and stored at -80 degrees C no longer than 6 months. A 5-percent DMSO concentration is comparable to a with 10-percent concentration in terms of recovery and MNC viability.
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 (p<0.001), respectively. Long-term hematologic recovery at 6, 12 and 24 months did not differ between the two groups studied and it was also comparable to standard rate-controlled freezing protocols. Factors influencing a faster neutrophil and platelet recovery in the multivariate analysis were infusion of more than 3 x 106/Kg of CD34+ cells and a viability >60%. 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.
4644 INTRODUCTION Despite the advent of new antifungal agents, the prognosis of Invasive Fungal Infections (IFIs) in highly immunocompromised patients remains poor. The current Mycoses Study Group Infectious Diseases Society of America Guidelines do not recommend the use of combination antifungal therapy for the routine treatment of IFIs. However, the use of combination therapy has become very prevalent in treating seriously ill immunocompromised patients. The purpose of this study was to collect the clinical experience of 7 Spanish Haematology Departments in antifungal combination therapy. Thus, we retrospectively examined all antifungal combination therapies applied in patients diagnosed with proven or probable IFIs in our centers. The main goal was to determine efficacy, toxicity and mortality among combinations. PATIENTS AND METHODS We identified 52 patients (26 males and 26 females) who received antifungal combination therapy for more than a week in our institutions between October 2007 and May 2009. The mean age was 40.7 years (range: 2-73). The diagnosis of IFI was established according to the EORTC/MSG criteria. 31 patients were treated for haematological malignancies with high-dose chemotherapy for remission induction and the others 21 were undergone stem cell transplantation -9 HLA-identical sibling, 11 unrelated SCT, 1 autologous; the stem cells source was cord blood in 9 patients and 6 of the 21 receptors received reduced intensity conditioning regimen-. Underlying diseases were: 21 AML, 17 ALL, 7 MDS, 4 NHL, 1 MM, 1 CLL and 1 Biphenotypic Acute Leukemia. RESULTS 26 patients had a proven IFI -12 Invasive Lung Aspergillosis, 4 Candidemia (2 C. Krusei and 2 C. Tropicalis), 2 generalized Fusarium, 5 Mucormicosis (3 rinocerebral and 2 pulmonar), 1 generalized Scedosporium Apiospermun, 1 cerebral Cryptococcus and 1 generalized Geotrichum Capitatum- and 26 had a probable IFI (all Invasive Aspergillosis). All patients but 4 received antifungal prophylaxis, 9 with fluconazole, 18 with voriconazole, 15 with itraconazole, 2 with liposomal amphotericin B (AmB) and 2 with caspofungin. Antifungal combination therapy was: AmB + caspofungin in 17 patients; voriconazole + caspofungin in 15 patients; voriconazole + AmB in 15 patients; AmB + posaconazole in 4 patients and voriconazole + anidulafungin in 1 patient. Global mortality was 59.6% (31 patients) and mortality due to IFI was 32,6% (17 patients). The combination therapy was well tolerated and no patient had severe toxicity that leads to discontinue the antifungal treatment, although mild renal and liver toxicity were seen. 37 patients (71.1%) showed a favourable response (28 complete and 9 partial) while unfavourable response were seen in 15 patients (28.9%). When we analyzed the results among antifungal combinations, the response rate was: 82.4% in caspofungin + AmB group, 66.76% in voriconazole + caspofungin group and 60% in voriconazole + AmB group. In spite of the best response in caspofungin + AmB group there were no statistically significances compared with voriconazole + caspofungin (p=0,3, chi square test) and voriconazole + AmB ( p=0,16, chi-square test). In 83.6 % of patients response was accompanied with granulocytic recovery. CONCLUSIONS The prognosis of antifungal monotherapy for IFIs remains poor. In practice, clinicians are increasingly using antifungal combination therapy in highly immunocompromised patients although appropriate clinical trials evaluating this treatment have not been performed. Our findings show that combination therapy is well tolerated and good results are obtained with highly rates response in patients with this therapy. Future studies should be performed comparing antifungal combined therapy versus monotherapy and among different antifungal combinations. Disclosures: No relevant conflicts of interest to declare.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.