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Preparative Regimen (preparative + regimen)
Selected AbstractsCD41+ and CD42+ hematopoietic progenitor cells may predict platelet engraftment after allogeneic peripheral blood stem cell transplantationJOURNAL OF CLINICAL APHERESIS, Issue 2 2001T. Demirer Abstract The objective of this study was to quantify subpopulations of CD34+ cells such as CD41+ and CD42+ cells that might represent megakaryocyte (MK) precursors in peripheral blood stem cell (PBSC) collections of normal, recombinant human granulocyte-colony stimulating factor (rhG-CSF) primed donors and to determine whether there is a statistical association between the dose infused megakaryocytic precursors and the time course of the platelet recovery following an allogeneic PBSC transplantation. Twenty-six patients with various hematologic malignancies transplanted from their HLA identical siblings between July 1997 and December 1999 were used. All patients except one with severe aplastic anemia who had cyclophosphamide (CY) alone received busulfan-CY as preparative regimen and cyclosporine-methotrexate for GVHD prophylaxis. Normal healthy donors were given rhG-CSF 10 ,g/kg/day subcutaneously twice daily and PBSCs were collected on days 5 and 6. The median number of infused CD34+, CD41+ and CD42+ cells were 6.61 × 106/kg (range 1.47,21.41), 54.85 × 104/kg (5.38,204.19), and 49.86 × 104/kg (6.82,430.10), respectively. Median days of ANC 0.5 × 109/L and platelet 20 × 109/L were 11.5 (range 9,15) and 13 (8,33), respectively. In this study, the number of CD41+ and CD42+ cells infused much better correlated than the number of CD34+ cells infused with the time to platelet recovery of 20 × 109/L in 26 patients receiving an allogeneic match sibling PBSC transplantation (r = ,0.727 and P < 0.001 for CD41+ cells, r = ,0.806 and P < 0.001 for CD42+ cells, r = ,0.336 and P > 0.05 for CD34+ cells). There was an inverse correlation between the number of infused CD41+ and CD42+ cells and duration of platelet engraftment. Therefore, as the number of CD41+ and CD42+ cells increased, duration of platelet engraftment (time to reach platelet count of , 20 × 109/L) shortened significantly. Based on this data we may conclude that flow cytometric measurement of CD41+ and CD42+ progenitor cells may provide an accurate indication of platelet reconstitutive capacity of the allogeneic PBSC transplant. J. Clin. Apheresis. 16:67,73, 2001. © 2001 Wiley-Liss, Inc. [source] Long term follow-up of allogeneic stem cell transplantation in patients with myelodysplastic syndromes using busulfan, cytosine arabinoside, and cyclophosphamide,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2010Ehab Atallah We report here the 10-year follow-up of 86 patients who underwent allogeneic stem cell transplantation (ASCT) for myelodysplastic syndrome (MDS). All patients received the busulfan, cytosine arabinoside, and cyclophosphamide (BAC) preparative regimen which consisted of busulfan 16 mg/kg, cytosine arabinoside 8 g/m2 IV, and cyclophosphamide 120 mg/kg IV. Fifty-nine patients (69%) had de novo MDS; 26 (30%) had secondary MDS (treatment related), and one had a preceding aplastic anemia which progressed to MDS before transplant. Cytogenetics (80 patients) was classified as good (34%), intermediate (17%), or poor (42%). With a median follow-up for survivors of 124 months, the 10-year Kaplan-Meier estimates for overall survival (OS) was 43% (95% confidence interval [CI]: 31,53%). Cumulative nonrelapse mortality (NRM) and relapse was 43% (95% CI: 32,54%) and 19% (95% CI: 11,27%), respectively. No patient relapsed after 2 years. In patients with RAEB-T/AML, 10-year relapse-free survival (RFS), relapse, and NRM was 36%, 36%, and 27%, respectively. Younger age (P = 0.05), human leukocyte antigen (HLA) match (P = 0.002), good risk cytogenetics (P = 0.008), and having a related donor (P = 0.03) significantly improved overall and RFS in the multivariable analysis. The long-term follow-up of patients receiving the BAC regimen with ASCT in this study indicated durable relapse-free and OS with acceptable toxicity in this group of patients with high-risk features. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Reduced-intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicityPEDIATRIC TRANSPLANTATION, Issue 3 2003Jennifer E. Schwartz Abstract: The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non-neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen-related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure-related mortality but are at risk for non-fatal late effects of the high-dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced-intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced-intensity HCT (RI-HCT) relies on the use of immunosuppressive but non-myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen-related toxicities. Although the experience with RI-HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated-dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI-HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced-intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation. [source] Polyclonal anti-T-cell globulin as part of the preparative regimen for pediatric allogeneic stem-cell transplantationPEDIATRIC TRANSPLANTATION, Issue 4 2001Mats Remberger Abstract: To prevent graft rejection and graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation (ASCT), 56 children were given polyclonal anti-T-cell globulin (ATG) as part of the conditioning regimen. Of the 56 children in the cohort, 27 had a non-malignant disease and 29 had different hematological malignancies. Eight were in first remission of leukemia and the remainder in later stages. Donors were in 16 cases a human leucocyte antigen (HLA)-identical sibling and in 40 a matched unrelated donor (MUD). The control group comprised 16 patients with an HLA-identical donor; the children in this group were not treated with ATG. Side-effects related to the ATG treatment occured in 63% of the patients and included fever, chills, headache, dyspnoea, nausea/vomiting, body pain, fall in blood pressure, and transient respiratory arrest. Engraftment occured in 55 (98%) of the ATG-treated patients at a median of 17 (11,27) days after ASCT. One rejection occured at 23 days post-SCT. The probabilities of acute graft-versus-host disease (GvHD) of grades II,IV were 6% for patients with an HLA-identical donor, 12% for controls, and 26% for the MUD group. Chronic GvHD occured in 20%, 50%, and 50% of patients in the three groups, respectively. Transplant-related mortality rates at 100 days were 6%, 6%, and 7%, respectively. The 5-yr survival rate was 94% and 81% using sibling donors, with and without ATG respectively, and 53% using unrelated donors (p =,0.002). Disregarding donor type, among the ATG-treated patients 5-yr survival rates were 46% in patients with a malignant disease and 77% in non-malignant disorders. Relapse and relapse-free survival rates were 42% and 46%, respectively. Five out of 12 patients who showed an early full donor chimerism in the T-cell lineage developed acute GvHD of grades II,IV, compared to none out of 13 patients being mixed chimeras (p =,0.01). Hence, the use of polyclonal ATG as part of conditioning prior to ASCT in children is safe and the survival rate encouraging. [source] Allograft with unrelated donor accentuates the gastrointestinal toxicity associated with high-dose melphalan and total body irradiation preparative for bone marrow transplantation in childrenPEDIATRIC TRANSPLANTATION, Issue 4 2000K. Vettenranta Abstract: The use of high-dose melphalan ( l -phenyalalanine mustard or l -PAM) has been shown to be associated with both hematological and non-hematological toxicity. It has been employed in the conditioning for allogeneic stem cell transplants from related donors but experience on its use in the unrelated setting has not been reported. As an attempt to elucidate the role of high-dose l -PAM (210 mg/m2) and total body irradiation (TBI) as a preparative regimen for allogeneic marrow transplantation from matched unrelated donors, they were employed in an institutional pilot series of seven pediatric patients. When compared with recipients of unrelated marrow grafts conditioned using other regimens, those treated with high-dose l -PAM experienced a markedly more severe acute graft-vs.-host disease (GvHD). The overall incidence of grade III,IV acute GvHD was higher (86% vs. 14%) among those treated with l -PAM. As judged by gastrointestinal (GI) symptoms, clinically significant (stages ++ to ++++) gut GvHD was strikingly more prevalent among those treated with l -PAM (86% vs. 9%, p<0.005). Toxic mortality prior to day +100 was 29% in the l -PAM group and 9% in the non- l -PAM group of patients. With a mean follow-up of 21 months no increase in the incidence of chronic GvHD has been encountered among those conditioned with l -PAM. We conclude that the use of preparative L -PAM for allogeneic transplants from unrelated donors is associated with considerable procedure-related toxicity. We strongly suggest its use in this setting to be viewed with caution. [source] Survival and predictors of outcome in patients with acute leukemia admitted to the intensive care unitCANCER, Issue 10 2008Snehal G. Thakkar MD Abstract BACKGROUND. Predictors of outcome and rates of successful discharge have not been defined for patients with acute leukemia admitted to intensive care units (ICUs) in the US. METHODS. This is a retrospective analysis of 90 patients with acute leukemia (no history of bone marrow transplant) admitted to an ICU from 2001,2004. The primary endpoints were improvement and subsequent discharge from the ICU, discharge from the hospital, and 2-month survival after hospital discharge. Secondary endpoints were 6- and 12-month survival. Univariate and multivariate logistic regression analyses were performed to identify factors predicting outcome. RESULTS. The median age of patients was 54 years and 48 (53%) were male. The most common reason for ICU transfer for all patients was respiratory compromise. The majority of all patients (68%) were eventually placed on ventilator support and approximately half required pressors. During the ICU course, 29 patients (32%) improved and subsequently resumed aggressive leukemia management, and 24 patients (27%) survived to be discharged from the hospital. The 2-, 6-, and 12-month overall survival was 24 (27%), 16 (18%), and 14 (16%), respectively. Higher APACHE II score, use of pressors, undergoing bone marrow transplantation preparative regimen, and adverse cytogenetics predicted worse outcome. Newly diagnosed leukemia, type of leukemia, or age did not. CONCLUSIONS. One of 4 patients with acute leukemia survived an ICU admission to be discharged from the hospital and were alive 2 months later. A diagnosis of acute leukemia should not disqualify patients from an ICU admission. Cancer 2008. © 2008 American Cancer Society. [source] Reduced-intensity allogeneic hematopoietic cell transplantation: Graft versus tumor effects with decreased toxicityPEDIATRIC TRANSPLANTATION, Issue 3 2003Jennifer E. Schwartz Abstract: The potentially curative role of allogeneic hematopoietic cell transplantation (HCT) in neoplastic and non-neoplastic diseases is offset by the substantial risks of morbidity and mortality from complications of the intensive myeloablative and immunosuppressive preparative regimen. These regimen-related toxicities have restricted allogeneic HCT to young, otherwise healthy individuals without comorbid diseases. Pediatric patients undergoing conventional allogeneic HCT have lower procedure-related mortality but are at risk for non-fatal late effects of the high-dose pretransplant chemoradiotherapy, such as growth retardation, sterility and other endocrine dysfunction. Evaluation of reduced-intensity preparative regimens is the major focus of current clinical research in allogeneic HCT. Reduced-intensity HCT (RI-HCT) relies on the use of immunosuppressive but non-myeloablative agents that allow engraftment of donor cells, which provide adoptive allogeneic cellular immunotherapy and graft versus tumor (GVT) effects, with decreased regimen-related toxicities. Although the experience with RI-HCT in pediatric patients is very limited at this time, results in adults indicate that attenuated-dose preparative regimens allow older patients and those with organ dysfunction to undergo successful allogeneic HCT with acceptable morbidity and mortality. In adults, the potency of the allogeneic GVT effect varies among neoplastic diseases, with better results observed in patients with indolent hematological malignancies or renal cell carcinoma. The effectiveness of RI-HCT as treatment for children with hemoglobinopathies, chronic granulomatous disease and cellular immunodeficiencies is encouraging, and the role of reduced-intensity preparative regimens for allogeneic HCT in pediatric malignancies is under investigation. [source] Graft failure following reduced-intensity cord blood transplantation for adult patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006Hiroto Narimatsu Summary We reviewed the medical records of 123 adult reduced-intensity cord blood transplantation (RI-CBT) recipients to investigate the clinical features of graft failure after RI-CBT. Nine (7·3%) had graft failure, and were classified as graft rejection rather than primary graft failure; they showed peripheral cytopenia with complete loss of donor-type haematopoiesis, implying destruction of donor cells by immunological mechanisms rather than poor graft function. Three of them died of bacterial or fungal infection during neutropenia. Two recovered autologous haematopoiesis. The remaining four patients underwent a second RI-CBT and developed severe regimen-related toxicities. One died of pneumonia on day 8, and the other three achieved engraftment. Two of them died of transplant-related mortality, and the other survived without disease progression for 9·0 months after the second RI-CBT. In total, seven of the nine patients with graft failure died. The median survival of those with graft failure was 3·8 months (range, 0·9,15·4). Graft failure is a serious complication of RI-CBT. As host T cells cannot completely be eliminated by reduced-intensity preparative regimens, we need to be aware of the difficulty in differentiating graft rejection from other causes of graft failure following RI-CBT. Further studies are warranted to establish optimal diagnostic and treatment strategies. [source] | ||||||||||