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Unrelated Donor (unrelated + donor)
Selected AbstractsToxic epidermal necrolysis and hemolytic uremic syndrome after allogeneic stem-cell transplantationPEDIATRIC TRANSPLANTATION, Issue 6 2007Johan Arvidson Abstract:, TEN and HUS are challenging complications with excessive mortality after HSCT. We report the development of these two conditions in combination in a nine-yr-old boy after HSCT from an unrelated donor. TEN with skin detachment of more than 90% of body surface area developed after initial treatment for GvHD. Within a few days of admission to the burns unit, the patient developed severe hemolysis, hypertension, thrombocytopenia, and acute renal failure consistent with HUS, apparently caused by CSA. The management included intensive care in a burns unit, accelerated drug removal using plasmapheresis, and a dedicated multi-disciplinary team approach to balance immunosuppression and infections management in a situation with extensive skin detachment. The patient survived and recovered renal function but requires continued treatment for severe GvHD. Suspecting and identifying causative drugs together with meticulous supportive care in the burns unit is essential in the management of these patients and long-term survival is possible. [source] Early transplantation of unrelated cord blood in a two-month-old infant with Wiskott,Aldrich syndromePEDIATRIC TRANSPLANTATION, Issue 5 2007Tang-Her Jaing Abstract:, This report exemplified a success of unrelated CBT in a two-month-old boy with Wiskott,Aldrich Syndrome. Umbilical cord blood was chosen as the stem-cell source because of its immediate availability and reduced tendency to cause GVHD. The conditioning regimen was cyclophosphamide, busulfan, and antithymocyte globulin. GVHD prophylaxis consisted of cyclosporin and methylprednisolone. The patient received an HLA 1-locus-mismatched cord blood unit, and the total number of infused nucleated cells was 11.14 × 107/kg. Neutrophil engraftment was achieved on day +11, and a platelet count greater than 50 × 109/L was achieved on day +71. He is currently alive and doing well at nine months post-transplant and free of any bleeding episodes. This case suggests that unrelated donor CBT may be safe and technically feasible, even in early infancy, when an appropriately matched related or unrelated donor is unavailable. [source] Durable remission following a third allogeneic stem cell transplantation in a patient with repeatedly relapsing SAA.PEDIATRIC TRANSPLANTATION, Issue 3 2007The importance of stroma cells for sustained engraftment? Abstract:, Diagnosis of acquired AATP which finally progressed to SAA was established in an eight-yr-old boy. PBSCT from an HLA-identical unrelated donor using high numbers of CD34+ selected stem cells was performed and resulted in complete remission for almost two yr. However, SAA reoccurred with 100% donor hematopoiesis and was reversed by a second CD 34+ selected PBSCT from the same donor. Declining blood cell counts after an interval of two yr indicated second relapse. Chimerism analysis in PB and BM aspirates revealed a small autologous cell population of 4,12% and 2,11%, respectively. Finally, a third transplantation with unmanipulated BM from the same donor resulted in sustained remission with 100% donor hematopoiesis. The patient is in complete remission for more than five yr following the third SCT. Late graft failure or late graft rejection known to occur after transplantation of highly purified CD34+ cells, or even graft exhaustion caused by stromal dysfunction due to the underlying disease necessitated a third transplantation. Regardless of the cause of relapse, transplantation of unmanipulated BM instead of highly purified PBSCTs led to a permanent and stable engraftment in a third attempt after two previous PBSCTs. [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] Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantationAMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2007Shinichi Kako Abstract Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by a proliferation mainly of mature neutrophils. The prognosis is generally poor and an optimal therapeutic strategy remains to be determined. Allogeneic hematopoietic stem cell transplantation (HSCT) is expected to be the only curative therapy so far. We report a 46-year-old male with progressive CNL who underwent bone marrow transplantation from an HLA-matched unrelated donor. After engraftment was achieved on day 35, relapse of CNL was confirmed on day 50. The progression of CNL was very rapid afterward and infiltration to the central nervous system was observed. The Janus Kinase 2 (JAK2) V617F homozygous mutation was detected from the peripheral blood or bone marrow samples throughout the clinical course. From comparison with reports of successful HSCT for CNL in the literature, it was inferred that HSCT should be performed in a stable status before progression. Furthermore, JAK2 V617F-positive CNL may contain an aggressive disease entity in contrast to previous reports. Accumulation of experiences is required to establish a definite role of HSCT in the treatment of CNL and a prognostic significance of JAK2 mutation in CNL. Am. J. Hematol., 2007. © 2006 Wiley-Liss, Inc. [source] The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2007Giorgio La Nasa Summary The presence of the 14-bp insertion polymorphism of the human leucocyte antigen (HLA)-G gene (HLA-G) promotes immune tolerance through increased synthesis of HLA-G molecules. We investigated this polymorphism in a large cohort of 53 thalassaemia patients transplanted from an unrelated donor. Sixteen patients (30·2%) homozygous for the 14-bp deletion had a higher risk of developing acute graft-versus-host disease (aGvHD) than patients homozygous for the 14-bp insertion (,14-bp/,14-bp vs +14-bp/+14-bp: Relative Risk = 15·0; 95% confidence interval 1·59,141·24; P = 0·008). Therefore, the 14-bp polymorphism could be an important predictive factor for aGvHD following bone marrow transplantation. [source] Chronic graft- versus -host disease after allogeneic bone marrow transplantation from an unrelated donor: incidence, risk factors and association with relapse.BRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2007A report from the Japan Marrow Donor Program Summary Chronic graft- versus -host disease (GVHD) remains the major cause of late morbidity and mortality after allogeneic stem cell transplantation. We retrospectively analysed 2937 patients who underwent bone marrow transplantation from an unrelated donor (UR-BMT) facilitated by the Japan Marrow Donor Program (JMDP) and survived beyond day 100 after transplantation. The cumulative incidence of chronic GVHD (limited + extensive) or extensive chronic GVHD at 5 years post-transplant was 45·8% and 28·2%, respectively. On multivariate analysis, seven variables predicting chronic GVHD were identified: recipient age over 20 years, donor age over 30 years, primary diagnosis of chronic myeloid leukaemia, human leucocyte antigen (HLA)-A or -B mismatch, total body irradiation-containing regimen, platelet count not having reached 50 × 109/l by day 100, and prior acute GVHD. Among 2609 patients with haematological malignancy, overall survival was significantly higher in patients with limited chronic GVHD but lower in patients with extensive chronic GVHD compared with those without chronic GVHD. The cumulative incidence of relapse among patients with limited or extensive chronic GVHD was significantly lower than that among patients without chronic GVHD. Our results suggest that limited chronic GVHD provides a survival benefit to patients with haematological malignancies by reducing the risk of relapse without increasing the risk of death from chronic GVHD. [source] Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005AnnaCarin Horne Summary Haemophagocytic lymphohistiocytosis (HLH) poses major therapeutic challenges, and the primary inherited form, familial haemophagocytic lymphohistiocytosis (FHL), is usually fatal. We evaluated, including Cox regression analysis, survival in 86 children (29 familial) that received HLH-94-therapy (etoposide, dexamethasone, ciclosporin) followed by allogeneic stem cell transplantation (SCT) between 1995 and 2000. The overall estimated 3-year-survival post-SCT was 64% [confidence interval (CI) = ±10%] (n = 86); 71 ± 18% in those patients with a matched related donor (MRD, n = 24), 70 ± 16% with a matched unrelated donor (MUD, n = 33), 50 ± 24% with a family haploidentical donor (haploidentical, n = 16), and 54 ± 27% with a mismatched unrelated donor (MMUD, n = 13). After adjustment for potential confounding factors, estimated odds ratios (OR) for mortality were 1·93 (CI =0·61,6·19) for MUD, 3·31 (1·02,10·76) for haploidentical, and 3·01 (0·91,9·97) for MMUD, compared with MRD. In children with active disease after 2-months of therapy (n = 43) the OR was 2·75 (1·26,5·99), compared with inactive disease (n = 43). In children with active disease at SCT (n = 37), the OR was 1·80 (0·80,4·06) compared with inactive disease (n = 49), after adjustment for disease activity at 2-months. Mortality was predominantly transplant-related. Most HLH patients survived SCT using MRD or MUD, and survival with partially mismatched donors was also acceptable. Patients that responded well to initial pretransplant-induction therapy fared best, but some persisting HLH activity should not automatically preclude performing SCT. [source] A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood ,high-risk' acute lymphoblastic leukaemia: a study of the AIEOP groupBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2002Anna Maria Testi Summary. The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52·5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25·8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation. [source] Safety of allogeneic Epstein,Barr virus (EBV)-specific cytotoxic T lymphocytes for patients with refractory EBV-related lymphomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2002Qi Sun Summary. Epstein,Barr virus (EBV) causes lymphomas in immunocompromised individuals such as recipients of stem cell or organ transplants and patients with acquired immunodeficiency syndrome (AIDS). EBV has also been detected in the Reed,Sternberg cells of approximately 50% of all cases of Hodgkin's disease (HD). The purpose of this study was to examine the safety, and the clinical and immunological effects of infusing allogeneic EBV-specific cytotoxic T lymphocytes (CTL) for patients with refractory EBV-positive malignancies. In this pilot study, we have treated four patients with EBV-related lymphoma using allogeneic EBV-specific CTL. Two patients received EBV-specific CTL derived from partially human leucocyte antigen (HLA)-matched donors and the other two from HLA-matched siblings. No complications were observed as a result of the CTL infusions and all patients showed increased levels of EBV-specific CTL precursors (CTLp) post infusion. Of the two organ transplant patients, one had refractory disease and has sustained a complete remission following the T-cell infusions. The second has also been disease free since T-cell infusions, although the efficacy cannot be definitively attributed to CTL therapy because this patient received local radiation therapy prior to immunotherapy. A patient with AIDS-related, EBV-positive lymphoma had disease progression following CTL infusions. One HD patient received HLA 4/6 matched T cells from an unrelated donor and showed a decrease in the size of affected lymph nodes and resolution of B-symptoms post infusion. In conclusion, adoptive immunotherapy with allogeneic EBV-specific CTL is safe and mayhave efficacy in patients with high-risk or refractory EBV-related tumours. [source] Allogenic hematopoietic stem-cell transplantation with reduced-intensity conditioning in patients with refractory and recurrent multiple myelomaCANCER, Issue 15 2010Long-term follow-up Abstract BACKGROUND: Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for myeloma, but is reportedly associated with a high risk of nonrecurrence mortality (NRM). Reduced-intensity conditioning (RIC) allows for the reduction of NRM, but the recurrence rate is increased. The role and timing of allogeneic SCT in the disease course remains controversial. To the authors' knowledge, there are limited data regarding the long-term outcome of RIC in the recurrent/refractory setting. METHODS: A retrospective analysis was conducted of SCT outcomes in 50 patients who received RIC for recurrent/refractory myeloma between the years 2001 and 2004. All patients were given fludarabine-melphalan based conditioning and stem cell grafts from a related (n = 27) or unrelated donor (n = 23). RESULTS: The median age was 53 years. Forty-seven patients failed a prior autologous SCT. Thirty patients were in disease remission at the time of SCT and 20 had stable or progressive disease. With a median follow-up of 6.4 years (range, 5-7.9 years), the overall and progression-free survival (PFS) rates were 34% and 26%, respectively. The NRM rate was 26%. Adverse prognostic factors for survival included SCT not in remission, long duration of disease (>5 years from diagnosis), and transplantation from a female donor to a male recipient. The 7-year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic graft versus host disease and the achievement of complete remission after SCT were associated with improved outcome. CONCLUSIONS: Allogeneic SCT can result in long-term PFS in a subset of myeloma patients who fail prior therapy and should be considered early after failure and after achieving remission. Cancer 2010. © 2010 American Cancer Society. [source] Access to hematopoietic stem cell transplantationCANCER, Issue 14 2010Effect of race Abstract BACKGROUND: The purpose of the current study was to determine whether the use of hematopoietic stem cell transplantation (HCT) to treat leukemia, lymphoma, or multiple myeloma (MM) differs by race and sex. METHODS: The annual incidence of leukemia, lymphoma, and MM was estimated in the United States in people aged <70 years by race and sex using the Surveillance, Epidemiology, and End Results (SEER) cancer registry between 1997 and 2002 and US census reports for the year 2000. The annual incidence of autologous, human leukocyte antigen (HLA) identical sibling, and unrelated HCT performed in these groups was estimated using Center for International Blood and Marrow Transplant Research data from 1997 through 2002. Logistic regression analysis was used to calculate the age-adjusted odds ratio (OR) of receiving HCT for Caucasians versus African Americans and for men versus women. RESULTS: The likelihood of undergoing HCT was found to be higher for Caucasians than for African Americans (OR, 1.40; 95% confidence interval [95% CI], 1.34-1.46). This difference existed for each type of HCT: autologous (OR, 1.24; 95% CI, 1.19-1.30), HLA identical sibling (OR, 1.59; 95% CI, 1.46-1.74), and unrelated donor (OR, 2.02; 95% CI, 1.75-2.33). Overall, men were more likely than women to receive HCT (OR, 1.07; 95% CI, 1.05-1.1 [P < .0001]); however, this difference was found to be significant only for autologous HCT (OR, 1.10; 95% CI, 1.07-1.13 [P < .0001]). CONCLUSIONS: HCT is more frequently used to treat leukemia, lymphoma, and MM in Caucasians than in African American individuals. African Americans have lower rates of both autologous and allogeneic HCT, indicating that donor availability cannot fully explain the differences. Women are less likely than men to receive autologous HCT for reasons unexplained by age or disease status. Cancer 2010. © 2010 American Cancer Society. [source] Combination therapy with tacrolimus and mycophenolate mofetil: effects of early and late minimization of mycophenolate mofetil after renal transplantCLINICAL TRANSPLANTATION, Issue 5 2008Rowan Walker Abstract:, The objectives of the study were: (i) to compare the efficacy and safety of minimizing mycophenolate mofetil (MMF) early (30 d) or late (90 d) after renal transplantation, when used in combination with tacrolimus; (ii) to retrospectively investigate factors associated with early, acute rejections and (iii) to investigate the pharmacokinetic interaction between tacrolimus and diltiazem. A prospective, randomized, multicenter, open-label study was conducted in 124 de novo kidney transplant recipients. Efficacy and safety outcomes were assessed for 180 d after transplantation and subjects were followed-up for a mean duration of 5.1 yr. The efficacy and safety outcomes were comparable whether the dose of MMF was minimized early or late. The incidence of early, acute rejection episodes was higher for recipients who were younger, received a graft from an unrelated donor or failed to achieve adequate tacrolimus concentrations (trough > 10 ng/mL) in the first seven d after transplant. Concomitant use of diltiazem had a tacrolimus-sparing effect in some subjects. Based on these results, we support the achievement of a high target tacrolimus concentration within the first week after renal transplant and suggest that early minimization of MMF can be achieved when used in combination with tacrolimus. [source] Treatment of CML in pediatric patients: Should imatinib mesylate (STI-571, Gleevec) or allogeneic hematopoietic cell transplant be front-line therapy?PEDIATRIC BLOOD & CANCER, Issue 5 2004Michael A. Pulsipher MD Abstract Background Long-term survival of pediatric patients with chronic myelogenous leukemia (CML) receiving myeloablative hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60 and 75%, but is associated with significant morbidity. Imatinib mesylate (STI-571, Gleevec) and reduced intensity conditioning stem cell transplantation (RIC) are two promising new tools that offer potential for decreasing therapy associated morbidity for patients with CML. Results Large trials have shown significant responses in chronic phase patients treated with imatinib and reasonable but short-lived responses in advanced phase CML. Data from adult studies is beginning to define populations likely to progress or have prolonged responses to imatinib, and some adult treatment paradigms are moving toward reserving transplantation until patients are at risk of failure with imatinib. Early trials of RIC transplantation in CML show decreased transplant related morbidity with efficacy similar to conventional transplantation, but the approach has yet to be verified in phase III studies. Data in pediatric patients with imatinib and RIC transplantation is limited. Conclusions Studies with imatinib are underway in pediatrics, but whether pediatric dosing schemes will lead to outcomes similar to adults is unknown. Because HLA-matched myeloablative transplantation offers a high rate of cure in the pediatric population, clinical studies assessing the role of imatinib mesylate and RIC transplantation should be planned carefully in order to avoid sub-optimal outcomes. © 2004 Wiley-Liss, Inc. [source] Unrelated cord blood transplantation in children with severe congenital neutropeniaPEDIATRIC TRANSPLANTATION, Issue 6 2009M. Akif Yesilipek Abstract:, SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG-CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG-CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA-matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 × 107/kg and CD34+ cell number was 3, 74 × 105/kg in Case 1. Those cell numbers were 8, 8 × 107/kg and 5, 34 × 105/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post-transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT. [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] Age- and sex-related patterns of serum interferon-, activity in lupus familiesARTHRITIS & RHEUMATISM, Issue 7 2008Timothy B. Niewold Objective Interferon-, (IFN,) levels are elevated in many patients with systemic lupus erythematosus (SLE) and may play a primary role in its pathogenesis. The purpose of this study was to determine whether serum IFN, activity in SLE patients and their healthy first-degree relatives is highest in early adulthood, when the incidence of SLE is greatest. Methods Serum samples from 315 SLE patients, 359 healthy first-degree relatives, and 141 healthy unrelated donors were measured for IFN, activity using a functional reporter cell assay. IFN, activity was analyzed in relation to age, and subgroups with high levels of IFN, activity were identified within the large data sets using a Mann-Whitney sliding window segmentation algorithm. The significance of each subgrouping was ranked by Kruskal-Wallis testing. Results Age was inversely correlated with IFN, activity in female SLE patients (r = ,0.20, P = 0.001) as well as their healthy female first-degree relatives (r = ,0.16, P = 0.02). In male patients and their healthy male first-degree relatives, there was no significant overall correlation between age and serum IFN, activity. The segmentation algorithm revealed significantly increased IFN, activity between the ages of 12 and 22 years in female SLE patients and between the ages of 16 and 29 years in male SLE patients. Both male and female healthy first-degree relatives had significantly decreased IFN, activity after the age of 50 years. Conclusion Serum IFN, activity is higher in younger individuals in the SLE family cohorts, and this tendency is accentuated in affected individuals. This age-related pattern of IFN, activity may contribute to the increased incidence of SLE in early adulthood, and interestingly, males and females had similar age-related patterns of IFN, activity. [source] Strategies for Establishing Organ Transplant Programs in Developing Countries: The Latin America and Caribbean ExperienceARTIFICIAL ORGANS, Issue 7 2006José Osmar Medina-Pestana Abstract:, The Latin America and Caribbean region is composed of 39 countries. It is remarkable the progress of transplantation in the region in despite of the low economic resources when compared to other regions. The criteria for brain death are well established and culturally accepted. The consent for retrieval is based on required family consent in most countries. The regulations for living donors are also well established, with restrictions to unrelated donors and prohibition of any kind of commerce. The access to transplant is limited by the model of public financing by each country, and those with public universal coverage have no financial restrictions to cover the costs for any citizen; in countries with restricted coverage, the access is restricted to the employment status. There is a progressive increment in the annual number of solid organ transplants in Latin America, reaching near 10 000 in 2004, accomplished by adequate legislation that is also concerned with the prohibition of organ commerce. [source] Preliminary evidence that the allogeneic response might trigger antitumour immunity in patients with advanced prostate cancerBJU INTERNATIONAL, Issue 5 2006Gordon Muir OBJECTIVE To explore the possibility that allogeneic responses might, by chance, encompass cross-reactive T cell clones specific for neo-antigenic tumour determinants, and thereby activate antitumour immunity; such cross-reactions are well documented for antiviral immunity, and genetic instability in developing cancers generates many neo-antigenic determinants as potential targets for immune responses, but the biology inevitably favours tumour progression. PATIENTS AND METHODS Fourteen patients with hormone-refractory prostate cancer received full-thickness skin allografts from different, unrelated donors (fellow patients) until each had received six grafts. Serum prostate-specific antigen (PSA) level was used as a surrogate for tumour mass. RESULTS One patient had a remarkable decline in PSA level, with levels at 1 year lower than before grafting. A second patient had stable PSA levels for almost 2 years. A third patient had stable PSA levels for 10,12 months before they resumed an exponential rise. Of four patients with PSA levels of >10 ng/mL, three required surgery or radiotherapy for obstructive symptoms during or shortly after grafting. CONCLUSION Transplant rejection involves mechanistically atypical T cell recognition of allogeneic major histocompatibility complex antigens, with massive polyclonal T cell activation. This unique aspect of T cell biology might represent a novel approach for initiating cross-reactive antitumour responses. [source] Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005Nicolaus Kröger Summary A prospective pilot study was performed to evaluate the effect of reduced-intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti-thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis. The median age of the patients was 53 years (range, 32,63). No primary graft failure occurred. The median time until leucocyte (>1·0 × 109/l) and platelet (>20 × 109/l) engraftment was 16 (range, 11,26) and 23 d (range, 9,139) respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%). Acute graft- versus -host disease (GvHD) grades II,IV and III/IV occurred in 48% and 19% of cases and 55% of the patients had chronic GvHD. Treatment-related mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0,32%] at 1 year. Haematological response was seen in 100% and complete histopathological remission was observed in 75% of the patients and 25% of the patients showed partial histopathological remission with a continuing decline in the grade of fibrosis. After a median follow-up of 22 months (range, 4,59), the 3-year estimated overall and disease-free survival was 84% (95% CI: 67,100%). [source] Varicella-zoster virus infection in adult patients after unrelated cord blood transplantation: a single institute experience in JapanBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2003Akira Tomonari Summary. Varicella-zoster virus (VZV) infection was studied in 40 adult patients who underwent cord blood transplantation (CBT) from unrelated donors. Twenty-five patients developed VZV reactivation at a median of 5 months after CBT (range 1·7,26 months). The cumulative incidence of VZV reactivation after CBT was 80% at 30 months. Twenty-two patients developed localized herpes zoster. The remaining three patients developed atypical non-localized herpes zoster, which was associated with visceral dissemination in one patient. All the patients responded well to antiviral therapy. Unexpectedly, the absence of grade II,IV acute graft-versus-host disease (GVHD) was associated with a higher rate of VZV reactivation after CBT (100% versus 55%, P = 0·01). These results suggest that recovery of VZV-specific immune responses after CBT is delayed even in patients without severe acute GVHD. [source] Efficacy of etoposide, cyclophosphamide, and total body irradiation in allogeneic bone marrow transplantation for adult patients with hematological malignanciesCLINICAL TRANSPLANTATION, Issue 5 2004Tomomi Toubai Abstract:, Introduction:, A combination of fractionated total body irradiation (TBI) with etoposide (VP-16) and cyclophosphamide (CY) as a preconditioning regimen (VP/CY/TBI) has been reported to be safe and effective for both adults and children undergoing allogeneic bone marrow transplantation (allo-BMT). However, the reported doses of VP-16 were different. We evaluated the efficacy and safety of a VP-16 (at less than the usual dose)/CY/TBI regimen for adults with hematological malignancies who are required to receive allo-BMT. Patients and methods:, Thirty-eight patients received VP-16, CY and TBI (VP/CY/TBI) as a preconditioning regimen for allo-BMT. Twenty-one patients were in first complete remission (1CR), six patients were in second remission (2CR) and 11 patients were in non-remission status (non-CR) before allo-BMT. These patients received allo-BMT from related donors (n = 14) and unrelated donors (n = 24). The preconditioning regimen consisted of VP-16 (15 mg/kg/d for 2 d), CY (60 mg/kg/d for 2 d) and 12 Gy TBI in six fractions for 3 d. Results:, Two patients died on day 30 after transplantation. The median follow-up period for all patients was 35.0 months (range 0.8,159.6 months). At the time of analysis, 10 patients had died. Seven of those 10 patients died because of relapse. The estimated 5-yr disease-free survival (DFS) rates for all cases and acute myelogenous leukemia and acute lymphoblastic leukemia cases were 73.6, 66.7 and 100%, respectively. The estimated 5-yr DFS rates for 1CR, 2CR and non-CR cases were 90.5, 83.3 and 40.9%, respectively (p < 0.05). Conclusion:, Based on these findings, we suggest that a VP/CY/TBI regimen is effective and safe for adult patients with hematological malignancies in 1CR and 2CR. [source] | |||||||||||||||||||||||||