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)

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.
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PMID:Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia. 772 69

Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.
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PMID:Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia. 870 95

This study reviews results of a radiation-free preparative regimen consisting of busulfan and cyclophosphamide in 65 unrelated allogeneic bone marrow transplant recipients. Thirty-eight patients had chronic myelogenous leukemia (17 patients chronic phase, 13 patients accelerated phase, eight patients blast phase), 19 patients had acute leukemia (second complete remission or relapse) and eight patients had myelodysplasia. The patients were transplanted at four different medical centers from July 1988 to November 1992. Ages ranged 4-48 years (median 32). Fifty-seven patients received busulfan 16 mg/kg and cyclophosphamide 120 mg/kg, and eight received busulfan at doses between 15 and 17 mg/kg and cyclophosphamide at doses 100-200 mg/kg as preparative regimens. All patients received cyclosporine for graft-versus-host disease prophylaxis; in addition 46 patients received corticosteroid, 38 methotrexate, six anti-CD5 ricin A-immunotoxin, and four T cell-depleted bone marrow. Median follow-up of survivors was 53 months (range 15-68 months). Four year actuarial survival was 24 +/- 12%. Four-year survival based on disease was 29 +/- 27% for chronic myelogenous leukemia (CML) in chronic phase, 20 +/- 9% for chronic myelogenous leukemia in accelerated phase, 0% for chronic myelogenous leukemia in blast phase, 32 +/- 40% for acute leukemia, and 38 +/- 34% for myelodysplasia. Actuarial survival was 66 +/- 40% in patients age < 20 years, vs 23 +/- 13% for patients ages 20 to 40, and 10 +/- 14% for patients age > 40 years. Fifty patients (88%) engrafted. Graft failure occurred in eight patients. Acute graft-versus-host disease grade II-IV occurred in 36 (72%). Two patients relapsed after engraftment with the donor cells and died of leukemia within a month of relapse. The most common causes of death were graft-versus-host disease (37%), and transplant-related toxicity (59%); relapse (4%) was a rare cause of death. Busulfan/cyclophosphamide is an effective preparative regimen in unrelated bone marrow transplantation permitting adequate engraftment and a low relapse rate. Best results are observed in patients less than 20 years old.
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PMID:Unrelated allogeneic bone marrow transplantation using high-dose busulfan and cyclophosphamide (BU-CY) for the preparative regimen. 873 82

In order to analyze the incidence and risk factors for invasive fungal infection (IFI) after allogeneic BMT, 142 consecutive adult BMT recipients (131 sibling donors, 11 unrelated donors) transplanted in 1989-1993 were retrospectively analyzed. There were 21 cases with definite or probable IFI (incidence 15%) (Aspergillus, 15; Candida, four; Fusarium, one; Absidia, one). The median time to the diagnosis of IFI was 136 days after BMT (range 6-466 days). Only 14% of the IFIs were found during the neutropenic period post-BMT. Of the pretransplant characteristics, hematological disease (MDS vs other) (P = 0.001) and unrelated donor (P = 0.01) were risk factors for IFI. Acute GVHD grade III-IV (P = 0.03) and extensive chronic GVHD (P = 0.0002) were also found to be significant risk factors. Only three patients with IFI (14%) became long-term survivors. Invasive fungal infections tended to develop late after BMT, were usually caused by Aspergillus sp., and were strongly associated with GVHD and its treatment. Better prophylaxis and treatment of IFI are needed. More effective prophylaxis for GVHD might decrease the risk of IFI after allogeneic BMT.
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PMID:Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients. 913 72

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.
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PMID:Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. 919 77

High-dose therapy and allogeneic matched sibling bone marrow transplantation (BMT) is considered to be the treatment of choice for children with relapsed acute lymphoblastic leukemia (ALL), or for children with acute myeloid leukemia (AML) in first remission. However, the rate of bone marrow relapse after transplant for either of these diseases remains high. In this study, we assessed the efficacy and toxicity of high-dose cytosine arabinoside and total body irradiation (TBI) followed by allogeneic BMT, for children with acute leukemia or myelodysplastic syndrome (MDS). Sixty-five pediatric patients underwent allogeneic related (n = 57) or unrelated (n = 8) BMT. Twenty-seven were transplanted for ALL in second remission (CR2), and 16 for AML in first remission (CR1). The other 22 were high risk patients: six were transplanted for ALL in third remission (CR3), two for AML in CR2, two for myelodysplastic syndrome (MDS) and 12 for acute leukemia in relapse. Patients were prepared with cytosine arabinoside 3000 mg/m2 per dose twice daily for 6 days followed by 12000 cGy TBI as 200 cGy fractions twice daily for 3 days. Minimum follow-up is 21 months. Five-year event-free survival (EFS) and the actuarial relapse rate is 59 and 14% for patients with ALL in second remission, and 38 and 14+% for patients with AML in first remission. Twelve patients have relapsed (three are alive in remission after testicular or marrow relapse) and 28 have died of other causes. Acute GVHD with or without infection was the cause of death in 11 patients. Ten of the 11 patients who died of acute GVHD were considered at 'high risk' for GVHD (inadequate GVHD prophylaxis, or mismatched family donor or a matched unrelated donor). Toxicities in the immediate post-BMT period included diarrhea, oropharyngeal mucositis and conjunctivitis. Significant late toxicities included short stature, avascular necrosis of bone, and poor school performance (most often in patients who had received prior cranial irradiation). Our conclusions are that high-dose Ara-C and TBI followed by allogeneic bone marrow transplantation is effective therapy for children in second complete remission of their acute leukemia. However, significant late toxicities occur, and it is clear that more effective, less toxic therapies are necessary for these patients.
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PMID:Allogeneic bone marrow transplantation for children with acute leukemia: long-term follow-up of patients prepared with high-dose cytosine arabinoside and fractionated total body irradiation. 923 49

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.
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PMID:Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients. 957 Jun 80

We analyzed results of 40 infants less than 2 years of age who received bone marrow transplants (BMT) between May 1974 and January 1995 for treatment of acute myelogenous leukemia (AML; N = 34) or myelodysplastic syndrome (MDS; N = 6) to determine outcome and survival performance. Among the AML patients, 13 were in first remission, 9 were in untreated first relapse or second remission, and 12 were in refractory relapse. Patients were conditioned with cyclophosphamide in combination with either total body irradiation (TBI; N = 29) or busulfan (N = 11). Source of stem cells included 6 autologous donors, 15 HLA genotypically identical siblings, 14 haploidentical family members, and 5 unrelated donors. Graft-versus-host disease (GVHD) prophylaxis was methotrexate (MTX) for 17, MTX plus cyclosporine (CSP) for 14, or CSP plus prednisone for 3. Incidence of severe (grade 3-4) regimen-related toxicity was 10% and transplant-related mortality was 10%. Acute GVHD (grades II-III) occurred in 39% of allogeneic patients, and chronic GVHD developed in 40%. Relapse, the most significant problem for patients in this study, occurred in 1 MDS patient and 23 AML patients and was the cause of death for 19 patients. The 2-year probabilities of relapse are 46%, 67%, and 92%, respectively, for patients transplanted in first remission, untreated first relapse or second remission, and relapse. One MDS and 8 AML patients received second marrow transplants for treatment of relapse, and 5 of these survive disease-free for more than 1.5 years. All 6 MDS patients and 11 of 34 AML patients survive more than 1.5 years later. The 5-year probabilities of survival and disease-free survival are 54% and 38% for patients transplanted in first remission and 33% and 22% for untreated first relapse or second remission. None of the patients transplanted with refractory relapse survive disease-free. Outcome was significantly associated with phase of disease at transplantation and pretransplant diagnosis of extramedullary disease. Long-term sequelae included growth failure and hormonal deficiencies. Survival performance was a median of 100% (80% to 100%) and neurologic development for all survivors was appropriate for age. This study indicates that infants with AML have similar outcome after BMT compared with older children and that BMT should be performed in first remission whenever possible. In addition, allogeneic BMT provides effective therapy for the majority of infants with MDS.
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PMID:Bone marrow transplantation for children less than 2 years of age with acute myelogenous leukemia or myelodysplastic syndrome. 980 46

Between February 1995 and August 1997, 11 children (eight males, three females) aged 4-16 years (median 7 years) underwent allogeneic PBPC transplantation for treatment of hematological disorders. Seven patients with acute leukemia (n = 5 ALL, n = 1 AML) or lymphoma (n = 1) received primary allogeneic PBPC transplantation, four patients received a second allotransplantation for graft failure (n = 1 AML, n = 1 sickle cell anemia) or disease recurrence (n = 1 ALL, n = 1 MDS). Five donors were HLA-identical siblings, five were 0-1 antigen mismatched family members and one was a matched unrelated donor. Donors received G-CSF 10-12 microg/kg/day for 3-7 days, and underwent one or two leukaphereses. The median cell yield per donor expressed per kg of recipient body weight was as follows: mononucleated cells 10.8 x 10(8)/kg (range 4.7-21.2); CD34+ cells 8.6 x 10(6)/kg (range 3.2-22); CD3+ cells 3.7 x 10(8)/kg (range 2.7-7.5). All patients achieved an ANC >0.5 x 10(9)/l after a median of 12 days (11-18). An unsupported platelet count >50 x 10(9)/l was reached 15 days (13-21) after PBPC transplantation; four patients failed to reach this threshold. Acute GVHD (aGVHD) grades II to IV occurred in eight (73%) patients: seven of them experienced grade III-IV aGVHD. Seven patients evaluable for chronic GVHD (cGVHD) were scored as absent in five, limited in one and extensive in one patient. As of September 1997, six patients (55 %) were alive between 60 and 938 days post-transplant (median follow-up 274 days); four patients with malignancy were alive in CR after primary allotransplantation, two patients were alive after a second PBPC transplant. Five patients have died with the main causes of death being aGVHD (n = 3), ARDS (n = 1), relapse of the underlying disease (n = 1). In conclusion, despite the limited number of patients, these preliminary results indicate that PBPC may be considered as an alternative to bone marrow for allografting also in children.
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PMID:Allogeneic transplantation of peripheral blood progenitor cells in children: experience of two pediatric centers. 998 87

Allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) has in recent years become an alternative to allogeneic bone marrow transplantation because it facilitates rapid hematopoietic reconstitution without an increase in the incidence of severe graft-versus-host disease (GVHD). We report on a 61-year-old man with myelodysplastic syndrome (MDS) and myelofibrosis who received an allo-PBSCT from his HLA-matched 68-year-old brother. The preparative regimen consisted of busulfan and cyclophosphamide. Cyclosporin A and methotrexate were administered for GVHD prophylaxis. The donor was treated with granulocyte colony-stimulating factor (G-CSF) at a dose of 10 micrograms/kg/day subcutaneously for 4 consecutive days. A preparation of 4.04 x 10(6) CD34+ cells/kg recipient weight was collected in a single apheresis and infused immediately. Engraftment times to a neutrophil count greater than 500/microliter and platelet count greater than 2.0 x 10(4)/microliter were 15 days each. Acute GVHD of grade II developed, but was resolved with methylprednisolone. However, the patient died of thrombotic microangiopathy 97 days after his allo-PBSCT. Administration of G-CSF and apheresis in the donor were feasible and well tolerated. Allo-PBSCT may result in earlier engraftment and be especially beneficial to elderly patients with MDS.
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PMID:[Allogeneic peripheral blood stem cell transplantation in an elderly patient with myelodysplatic syndrome with myelofibrosis]. 1006 93


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