Hematopoietic stem cell therapy for malignant diseases.
ABSTRACT Allogeneic bone marrow or blood stem cell transplantation (SCT) has changed its face in the last two decades. The introduction of nonmyeloablative conditioning regimens has reduced procedure toxicity and allowed the application of SCT in patients and conditions in which SCT was not offered in the past. In this review we will summarize the changes and accomplishments achieved in the past years in the field of stem cell transplantation for malignant disorders.
- SourceAvailable from: Kazuhiko Yamada[Show abstract] [Hide abstract]
ABSTRACT: We have previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reverses diabetic hyperglycemia in miniature swine. In order to test the potential clinical applicability of this strategy, we have extended it to a fully allogeneic nonhuman primate model. IKs were prepared in baboons by isolating islets from 50% to 70% partial pancreatectomies and injecting them under the autologous renal capsule, allowing vascularization before allogeneic Tx. Baboons with diabetes induced by stereptozotocin or total pancreatectomy, received composite IKs (n = 3) or free islets under the renal capsule or intraportally (n = 3), across fully allogeneic barriers with an immunosuppressive regimen consisting of ATG followed by MMF and tacrolimus. FBS of two of IK recipients decreased immediately after Tx and no insulin therapy was required throughout the experimental period (225 and 301 days). In contrast, all recipients of allogeneic free islets showed unstable FBS levels and required insulin within 2 months. We conclude that in addition to maintaining creatinine in the normal range, fully allogeneic IKs from single primate donors can achieve glucose regulation without insulin therapy, while free islets do not. These results support the feasibility of composite allogeneic IK Tx as a potential cure for end-stage diabetic nephropathy.American Journal of Transplantation 09/2011; 11(12):2603-12. DOI:10.1111/j.1600-6143.2011.03733.x · 6.19 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To assess the severity of xerostomia (subjective dry mouth) in haematopoietic stem cell transplantation (HSCT) patients and to investigate the association of xerostomia with other chronic oral complications. Cross-sectional study.Study participants and methods Participants were 48 patients with a history of HSCT recruited among members of the Dutch Stem Cell Transplantation Contact Group, and a comparison group of 41 age- and sex-matched individuals. Data were collected using the Xerostomia Inventory (XI score) and a seven-item oral health questionnaire. HSCT patients had a higher XI score than the comparison group, and a greater severity of several oral complaints: painful oral mucosa, altered taste, limited opening of the mouth and problems with tooth brushing. HSCT patients did not report greater pain during cold stimulation of teeth, chipped and cracked teeth or bleeding gums. In HSCT patients, the XI score correlated significantly with the severity of oral mucosal pain, altered taste, limited opening of the mouth, painful teeth following cold stimuli, chipped or cracked teeth, problems with tooth brushing and bleeding gums. In the comparison group, no correlations were observed between XI score and these oral problems. HSCT patients have more severe xerostomia, which is associated with other oral complaints. Dental professionals should monitor these patients post-transplant for oral complications. Symptoms of dry mouth should be relieved and secondary complications should be prevented.British dental journal official journal of the British Dental Association: BDJ online 11/2009; 207(9):E17; discussion 428-9. DOI:10.1038/sj.bdj.2009.977 · 1.09 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Abstract We conducted a phase I/II trial to assess the efficacy of cladribine, thiotepa, and antithymocyte globulin as a reduced intensity conditioning regimen for refractory or high-risk hematologic malignancy. The preparative regimen consisted of cladribine 5 mg/m(2)/day for 5 days, thiotepa 200 mg/m(2)/day for 3 days, and ATG 3 mg/kg/day (day -5) followed by allogeneic peripheral blood stem cell transplantation. Twelve patients were transplanted from an HLA matched family member. Two patients were treated at dose level I but both experienced grade IV dose limiting toxicities, therefore the thiotepa dose was reduced to 133 mg/m(2)/day (dose level II). Only 2 of the next 6 patients experienced dose limiting toxicities. Median age was 46 years. At dose level II, median time to neutrophil and platelet engraftment was 17 and 20 days, respectively. The incidence of acute and chronic GVHD was 40% and 30%, respectively. Day +100 non relapse mortality was 0% and at one-year was 20%. Median overall survival was 42 months and two-year OS was 70%. Median progression free survival was 11 months, and two-year PFS was 40%. We conclude that the reduced intensity conditioning regimen of cladribine, thiotepa, and ATG achieved excellent donor chimerism with acceptable toxicity.Leukemia & lymphoma 11/2012; 54(8). DOI:10.3109/10428194.2012.753444 · 2.61 Impact Factor