Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of alkylating agents (Alk), topoisomerase II inhibitors (Topo II) and radiotherapy (RT) can result in therapy-related myelodysplastic syndrome or acute myelogenous leukaemia (t-MDS/t-AML), the optimal treatment for which is allo-SCT. A retrospective review was performed of 24 patients who underwent related- or unrelated-donor SCT for t-MDS/t-AML at our institution. Eight patients remain alive and in continuous remission (median follow-up 54 months (range, 12-161)) with estimated 5-year EFS being 30% (95% confidence intervals 16-58%). Corresponding actuarial risks of relapse and non-relapse mortality (NRM) are 39% (19-60%) and 30% (13-50%), respectively. EFS was 40% in Alk/RT-related t-MDS/t-AML and 11% in Topo II-related t-MDS/t-AML (P=0.05), with an increased risk of relapse in the latter (56 vs 29%, respectively (P=0.05)). In multivariate analysis, development of acute GVHD (P=0.009) and Topo II-related t-MDS/t-AML (P=0.018) were associated with inferior EFS. Patients with acute GVHD had an increased risk of NRM (P=0.03) whereas risk of relapse was higher for patients of advanced age (P=0.046) and for patients who underwent bone marrow (vs blood) SCT (P=0.032). Allo-SCT can result in long-term survival for individuals with t-MDS/t-AML although outcome in Topo II-related t-MDS/t-AML patients remains suboptimal.
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PMID:Predictors of outcome following myeloablative allo-SCT for therapy-related myelodysplastic syndrome and AML. 1867 72

Donor lymphocyte infusions (DLI) often are used after allo-SCT to augment the graft-versus-tumor effect. Timing of infusion varies according to indication, for example to treat tumor recurrence, as a planned strategy to prevent disease relapse in the setting of T-cell-depleted grafts or non-myeloablative conditioning regimens, or as a method to convert mixed to full donor chimerism. The optimal strategy of timing, use of cytotoxic conditioning, cell dose and cell product composition, and so on, for DLI administration remains unclear. Despite varied techniques, DLI may lead to 3-year disease-free survivals (DFS) in excess of 60% for all CML patients and approach 90% in patients with only molecular or cytogenetic relapse. Other hematologic malignancies appear much less responsive, as less than 50% of patients respond and provide, at best, 3-year DFS rates of 20-50%. Multiple myeloma patients have overall response rates of 40-45% after DLI, suggesting benefit in relapsed disease, but limited experiences for diseases such as Hodgkin's lymphoma, myelodysplasia and ALL preclude recommendations for use of DLI at this time. Regardless of the indication, treatment-related mortality after DLI is 5-20% and more than one-third of patients will develop acute and/or chronic GVHD after DLI. The risks of these complications appear related, in part, to donor source, cell dose and therapy prior to DLI. Although there are no definitive answers, the information gleaned from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with bulky or aggressive disease may benefit from disease reduction prior to DLI.
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PMID:Donor lymphocyte infusions: the long and winding road: how should it be traveled? 1871 51

Bone marrow and stem cell transplantation in Jordan has been performed since the 1990s, but the first comprehensive program was established at King Hussein Cancer Center (KHCC) in March 2003. The program, in addition to other health care institutions in Amman, serves approximately 5.6 million Jordanians. Also, we treat several patients per year from neighboring Arab countries. The program at KHCC performs an average of 80 transplants per year. During the past 4 years 320 patients received transplants at KHCC; 26% of them received an autologous graft and 74% allogeneic grafts. Of the allogeneic grafts 91% were taken from matched family members, 6.7% were haploidentical from one of the parents, and 2.3% were from an unrelated donor or umbilical cord blood. The actuarial overall survival among all patients has been around 65%. The most common indication for transplantation at KHCC was leukemia/MDS followed by benign nonmalignant hematological/immune deficiency/metabolic disorders, with thalassemia major being the most common among this group. The cost of SCT is variable and depends on many factors including the type of transplant and the attending post-transplant complications. The average charge for autologous transplant (both adults and pediatrics) is 24,695 JD (one JD equals 1.42 USD), and the average charge for allogeneic transplant (both adults and pediatrics) excluding haploidentical transplant is 46,787 JD. We have not noticed any peculiar patterns of complications following BMT; however, we have seen a high incidence of chronic GVHD following minitransplant with fludarabine and single-dose TBI (Seattle protocol). At the inception of the program, invasive fungal infection mainly related to building construction, and central line complications were significant. Measures implemented to control such complications were successful to a large extent. We report our results to the EBMT group and we are accredited as an unrelated transplantation center. Although from a young program, our group has presented abstracts to international conferences.
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PMID:Bone marrow and stem cell transplantation at King Hussein cancer center. 1872 14

In developing countries, it is important to ascertain the safety of performing allogeneic hematopoietic SCT (HSCT) in single rooms without high-efficiency particulate air (HEPA) filters. We present our experience of performing 40 such transplants from July 2004 to November 2007. Source of stem cells was peripheral blood in 33, bone marrow in six and combined in one. G-CSF started from day +1. The indications were SAA-18, CML-7, AML-7, ALL-2, myelodysplastic syndrome-2 and thalassemia major-4. The median age was 19 years (range 2.2-46) with 29 male and 11 female participants. Antibacterial and antifungal prophylaxis was administered along with conditioning, and at the onset of fever, systemic antibiotics were started. Antifungal agents were added if fever persisted for 3 days. Median time for neutrophil engraftment was 10 days (range 8-17). Fever occurred in 38 (95%) for a median of 5 days (range 1-38), and blood cultures were positive in seven (17.5%). Systemic antibiotics were used in 95% and antifungals in 57.5% cases. The 30-day mortality was nil, and 100-day mortality was 1 (2.5%). After day 100, there were eight fatalities (20%) due to chronic GVHD-3, relapse-2, graft rejection-2, disseminated tuberculosis and aspergillosis-1. Our experience suggests that allogeneic HSCT can be safely performed in non-HEPA filter rooms in India.
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PMID:Allogeneic hematopoietic SCT performed in non-HEPA filter rooms: initial experience from a single center in India. 1879 72

The aim of the present study was to assess the influence of socioeconomic status (SeS) on the outcome of allo-SCT at a Brazilian SCT center. In total, 201 patients receiving HLA-identical related allo-SCTs were studied. The median age was 30 years. Overall, 163 patients had malignancies (CML 68, ALL/AML 63, myelodysplastic syndrome 12 and others 20). SeS was defined according to the Brazilian Association of Market Research Agencies classification, where people are clustered in groups A-E (richest to poorest). In total, 146 patients (72%) were classified as richest (A+B+C) and 55 (28%) as poorest (D+E). The D+E SeS group was associated with a higher incidence of chronic GVHD and acute GVHD (hazard ratio (HR)=2.61; P=0.001 and HR=2.62; P=0.001, respectively), better platelet and neutrophil engraftment (HR=1.94; P=<0.001 and HR=2.12; P=0.001) and with a higher TRM in multivariate analysis (HR=1.92; P=0.039). Estimated overall survival at 5 years was 55.2%. A D+E SeS (HR=2.13; P=0.001) was associated with a worse survival on multivariate analysis. In conclusion, a lower SeS is a strong prognostic factor in patients undergoing allo-SCT in Brazil, influencing engraftment, TRM and overall survival.
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PMID:Patient socioeconomic status as a prognostic factor for allo-SCT. 1897 20

The application of myeloablative Allo-SCT is limited by its associated morbidity and mortality. Reduced-intensity conditioning regimens attempt to diminish these, but are associated with a higher risk of disease relapse. Given the evidence of activity of clofarabine and cytarabine in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), we explored a novel reduced-intensity conditioning regimen based on this backbone. Patients received clofarabine 40 mg/m(2) i.v. on days -6 to -2, cytarabine 1 g/m(2) i.v. on days -6 to -2 and anti-thymocyte globulin (ATG) 1 mg/kg on day -4 and 2.5 mg/kg x 2 days on days -3 and -2. Seven patients were enrolled. Their median age was 54 years; three were with MDS and four with AML. The median duration of neutropenia was 14 days and that of thrombocytopenia was 22 days. Toxicities included hand-foot syndrome (57% grade 2), elevated alanine aminotransferase (ALT) (57% grade 3), elevated aspartate aminotransferase (AST) (86% grade 3) and hyperbilirubinemia (29% grade 3-5). No acute GVHD was observed. Enrollment to the trial was halted after three of the first seven patients expired on days +15, +26 and +32. Three of the four surviving patients have relapsed with a median TTP of 152 days. This regimen was not sufficiently immunosuppressive to ensure engraftment, and was associated with substantial morbidity and mortality.
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PMID:Allo-SCT conditioning for myelodysplastic syndrome and acute myeloid leukemia with clofarabine, cytarabine and ATG. 1913 40

Decitabine is a hypomethylating agent with activity in myelodysplastic syndrome (MDS). It is largely unknown whether treatment with this drug before allo-SCT will increase the toxicity of the preparative regimen or otherwise affect the results of the transplant. We report the outcome of 17 patients with MDS with a median age of 55.5 years (range, 36-66 years) who underwent an allo-SCT (12 siblings, 5 unrelated) after prior therapy with decitabine. Preparative regimens consisted of fludarabine in combination with BU (n=8) or melphalan (n=9). The source of stem cells was marrow in four patients and peripheral blood (PB) in 13 patients. Thirteen patients were in CR within 100 days of transplant. With a median follow-up of 12 months (range, 3-35 months), 11 patients are alive; eight in CR and three with progressive disease. Prior therapy with hypomethylating agents did not increase toxicity and may improve the outcome of allogeneic transplant in MDS and should be evaluated in a prospective trial.
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PMID:Feasibility of allo-SCT after hypomethylating therapy with decitabine for myelodysplastic syndrome. 1915 91

Therapies for myelodysplastic syndromes (MDS) often achieve hematological responses but their impact on overall survival has generally not been evaluated. The Duesseldorf MDS Registry allowed us to perform matched-pair analyses to assess a possible survival benefit of treatment with thalidomide, valproic acid, low-dose Ara-C, antithymocyte globulin (ATG), induction chemotherapy, or allogeneic stem cell transplantation (allo-SCT). For all treatment modalities, lengthening of survival was restricted to certain subgroups of patients. With the exception of allo-SCT, MDS treatment was generally palliative. Recently, epigenetic treatment with demethylating agents proved to be the first therapy that can significantly prolong survival in patients with higher-risk MDS.
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PMID:Impact on survival of different treatments for myelodysplastic syndromes (MDS). 1926 62

Allogeneic hematopoietic SCT (allo-HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Numerous myeloablative (MA), nonmyeloablative SCT (NST) and reduced conditioning transplant (RIC) studies have included MDS patients. Twenty-four MA HCT studies published from 2000 and 2008 reported OS and disease-free survival (DFS) ranging from 25 and 16% at 2 years to 52 and 50% at 4 years. In these publications, the incidence of grades II-IV acute GVHD was 18-100%, chronic GVHD 13-88%, relapse risk 24% at 1 year to 54.5% at 4 years and TRM 19% at day 100 to 61% at 5 years. From 2003 to 2008, 30 publications combining RIC and NST reported OS and DFS from 22 and 20% at 2 years to 79 and 79% at 4 years. Incidence of grades II-IV acute GVHD ranged from 9 to 63%, chronic GVHD 18 to 80%, relapse risk 6 to 61% and TRM 0% at day 100 to 34% at 5 years. The wide range in the published results leaves many unanswered questions. Although no ideal transplant conditioning has emerged, many of the MA and RIC studies used BU-based regimens and used a recipient age cutoff of 50-55 years for MA HCT. Similarly, there is no agreement on the use of induction or hypomethylating therapy before HCT, but azacitidine and decitabine are gaining increasing attention as a bridge to HCT. Until recently, the International Prognostic Scoring System (IPSS) dictated the use and timing of HCT. The WHO classification and WHO Prognostic Scoring System (WPSS) may be better suited in predicting the outcomes and should probably be incorporated in transplant algorithms. Most published MDS transplant series combine matched related donors (MRD) and matched unrelated donors (MUD). Umbilical cord blood (UCB) grafts will likely broaden the population of MDS patients eligible for allografting, but outcome data for MDS are scant. At this time, it is reasonable to consider the availability of an MRD or MUD as separate from an UCB graft in the decision of transplantation for MDS. The development of RIC, improvements in supportive therapy and alternative donor selection will provide better OS for MDS patients undergoing transplantation. Simultaneously, better understanding and medical therapy of MDS are leading us to re-examine patient selection and the timing of HCT. The results of HCT for MDS continue to improve together with the outlook of patients afflicted with myelodysplasia.
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PMID:The evolution of hematopoietic SCT in myelodysplastic syndrome. 1925 32

Haploidentical SCT (HaploSCT) has been most commonly performed using a myeloablative, TBI-based preparative regimen; however, the toxicity with this approach remains very high. We studied the feasibility of a reduced-intensity conditioning regimen in a phase II clinical trial using fludarabine, melphalan and thiotepa and antithymocyte globulin (ATG) for patients with advanced hematological malignancies undergoing T-cell depleted HaploSCT. Twenty-eight patients were entered in the study. Engraftment with donor-derived hematopoiesis was achieved in 78% of patients after a median of 13 days. Six patients experienced primary graft failure, three out of four tested patients had donor-specific anti-HLA antibodies (DSA) (P=0.001). Toxicity included mostly infections. A total of 21 out of 22 patients with AML/myelodysplastic syndrome (MDS) achieved remission after transplant (16 with relapsed/refractory AML). Five out of the 12 patients (42%) with AML/MDS with <15% BM blasts survived long term as compared with none with more advanced disease (P=0.03). HaploSCT with this fludarabine, melphalan and thiotepa and ATG RIC is an effective, well-tolerated conditioning regimen for patients with AML/MDS with low disease burden at the time of transplant and allowed a high rate of engraftment in patients without DSA. Patients with overt relapse fared poorly and require novel treatment strategies.
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PMID:Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT. 1966 37


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