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

In the literature 63 patients with myelodysplastic syndromes (MDS) are reported who were treated with syngeneic or allogeneic bone marrow transplantation. 62 patients were prepared for BMT with TBI containing regimens or Busulfan/Cyclophosphamide. GvHD prophylaxis was heterogenous. 33/63 patients are alive and well between 4 and 132 months after BMT. 23/63 patients died due to GvHD (n = 6), interstitial pneumonitis (n = 6), other infections (n = 4), toxicity of the preparative regimen (n = 5) or graft failure (n = 2). 9/63 patients relapsed between 2 and 98 (in median 6) months after BMT. There seems to be a correlation between the subtype of the MDS and the relapse rate: only 1/18 patients with RA/RARS relapsed compared to 7/42 patients with RAEB/RAEB-T. These results indicate that marrow transplantation can induce long term survival and may result in cure of patients with MDS.
 ...
PMID:Allogeneic bone marrow transplantation for myelodysplastic syndromes (MDS). 269 17

Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high-risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.
 ...
PMID:Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. 331 Dec 3

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.
 ...
PMID:Unrelated allogeneic bone marrow transplantation using high-dose busulfan and cyclophosphamide (BU-CY) for the preparative regimen. 873 82

We report an 11-year old female with myelodysplastic (refractory anemia with excess of blasts) presentation of Fanconi anemia. After failure of initial chemotherapy with low doses of 6-mercaptopurine and prednisolone she underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched sibling. Busulfan 8 mg/kg and cyclophosphamide 40 mg/kg were used as conditioning. The post-transplant course was uneventful with fast trilineage engraftment and mild cutaneous acute GVHD. She is alive 17 months after BMT with full hematological reconstitution without evidence of MDS.
 ...
PMID:Intermediate-dose busulfan and cyclophosphamide as a conditioning regimen for bone marrow transplantation in a case of Fanconi anemia in myelodysplastic transformation. 905 Dec 50

Graft versus host disease (GVHD) and recurrence of basic disease are major obstacles to a successful allogeneic bone marrow transplantation (BMT) outcome. One of the possibilities of maintaining the therapeutic potential of marrow allografting in the absence of GVHD is to intensify the conditioning regimen administered pre-T-cell depleted BMT in order to compensate for the loss of GVH related graft versus leukemia (GVL) effect. In order to do so we used a preparative regimen consisting of three alkylating agents-Busulfan (BU), Thiotepa (TTP) and Cyclophosphamide (CY)-for T-cell depleted allogeneic stem cell transplantation (SCT) instead of the standard BU-CY protocol. The effect of this intensified regimen was investigated in 30 consecutive leukemia patients who underwent T-cell depleted SCT from HLA identical siblings. Sixteen of the patients were males and 14 females, of median age 24 (5-43) years. Fourteen patients had acute myelogenous leukemia (AML), ten acute lymphoblastic leukemia (ALL), four chronic myelogenous leukemia (CML) and two myelodysplastic syndrome. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was normal, with WBC >1.0x10(9)/l at day +18 (10-32), ANC >0.5x10(9)/l at day +21 (9-33) and platelets >25x10(9)/l at day +30 (14-69). Regimen related toxicity (RRT) was moderate and transplant related complications comparable to other conventional conditioning protocols. Overall survival and disease free survival (DFS) at 60 months follow up was 50%. Only three patients (10%), with ALL, relapsed and subsequently died. From the current data it would appear that TTP does not significantly improve BMT outcome in patients with leukemia, when compared to the standard BU-CY conditioning. However, our results with the BU-TTP-CY combination followed by T-cell depleted allogeneic SCT could provide the basis for a prospective randomized study comparing this protocol with the standard BU-CY regimen.
 ...
PMID:The role of thiotepa in allogeneic stem cell transplantation in patients with leukemia. 1057 41

Patients who undergo autologous bone marrow transplantation for acute leukemia are at high risk for relapse. We have evaluated the feasibility of administering cell-mediated immunotherapy with family-related haploidentical lymphocytes following autologous bone marrow transplantation in order to evoke a graft-vs-leukemia effect in the autologous setting.Twenty-six patients aged 1.5-48 years were enrolled in this study. Eighteen suffered from acute myeloid leukemia, seven from acute lymphoblastic leukemia, and one from myelodysplastic syndrome. Eleven patients were transplanted in first remission, six in second remission, one in fourth remission, and eight in relapse. Conditioning consisted of Busulfan/Cyclophosphamide or Busulfan/Thiotepa/Cyclophosphamide. Nineteen patients (Group A) were treated with gradual increments of haploidentical donor T cells, starting on day +1, with an additional course of T cells plus intravenous recombinant human interleukin-2 one month later if no signs of graft-vs-host disease developed in the interim. Seven patients (Group B) were treated with high-dose haploidentical T cells on day +1 in conjunction with intravenous recombinant human interleukin-2. Donor cells were detected in the peripheral blood of both groups 12-48 hours post-cell-mediated immunotherapy, peaking at 48 hours. Three patients in Group A developed transient Grade I graft-vs-host disease. One patient in Group B developed Grade I, and three Grade IV, graft-vs-host disease. Group A patients engrafted normally, but the Group B patients with Grade IV graft-vs-host disease showed no signs of engraftment. Our results show that it is feasible to induce graft-vs-host disease in the autologous stem cell transplantation setting. However, the high-dose regimen of haploidentical T cells in conjunction with interleukin-2 results in severe toxicity and nonengraftment.
 ...
PMID:Adoptive immunotherapy with haploidentical allogeneic peripheral blood lymphocytes following autologous bone marrow transplantation. 1106 70

The graft-vs-tumor effect is an important part of the curative potential of allogeneic transplantation. We characterized the effect of transplanted donor mononuclear cells on relapse- and event-free survival after allogeneic bone marrow transplantation (BMT). We studied 113 consecutive patients with hematologic malignancies who received non-T-cell-depleted BMT from human leukocyte antigen (HLA)-matched siblings. Most patients (n = 103) received busulfan (Myleran)-based conditioning, and all patients received standard short-course methotrexate and tacrolimus (Prograf) as graft-vs-host disease prophylaxis. Sixty-four patients had low-risk diagnoses (acute lymphoblastic leukemia/acute myeloid leukemia [first complete remission], myelodysplastic syndrome [refractory anemia/refractory anemia with ring sideroblasts], and chronic myeloid leukemia [first chronic phase]); 49 patients had high-risk diagnoses (all others). Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3-positive T cells, CD34-positive hematopoietic cells, and type 2 dendritic cells (DC2) as covariates for event-free survival, relapse, and nonrelapse mortality. Recipients of larger numbers of DC2 cells had significantly lower event-free survival, a lower incidence of chronic graft-vs-host disease, and an increased incidence of relapse. Recipients of larger numbers of CD34-positive cells had improved event-free survival; recipients of fewer CD34-positive cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, content of donor DC2 cells was associated with decreased chronic graft-vs-host disease and graft-vs-leukemia effects consistent with Th2/Tc2 polarization of donor Tcells following allogeneic bone marrow transplantation.
 ...
PMID:DC2 effect on survival following allogeneic bone marrow transplantation. 1182 82

We have analyzed the plasma pharmacokinetics of busulfan in 272 patients receiving high-dose oral busulfan and intravenous cyclophosphamide in conjunction with allogeneic or autologous bone marrow transplantation. The patients ranged in age from 2 months to 59 yr (mean 10, median 12 yr) and had the following diagnoses: thalassemia or sickle cell anemia (n = 74); leukemia or myelodysplasia (n = 112); inborn errors of metabolism (n = 41) or immunodeficiency (n = 45). Plasma specimens were collected following the first dose for each patient which ranged from 1 to 4 mg/kg (mean +/- SD, 1.21 +/- 0.41, median 1.15). Busulfan was quantitated using ultraviolet absorbance detection after derivatization and HPLC separation. Pharmacokinetic parameters were derived by modeling the raw data to fit first-order single compartment kinetics. The kinetic parameters showed wide interpatient variability independent of age and diagnosis. There was a statistically significant correlation of age with the following parameters: area under the curve (AUC); maximal concentration; minimum concentration; clearance; volume of distribution and absorption half-time. The coefficients of determination (i.e. correlation coefficient squared) were low ranging from 0.04 to 0.12 implying only a small part (i.e. 4-12%) of the variance was explained by age. Although busulfan pharmacokinetics are age-related most of the variability is not explained by age or diagnosis.
 ...
PMID:Plasma pharmacokinetics of high-dose oral busulfan in children and adults undergoing bone marrow transplantation. 1260 88

To explore feasibility and efficacy of unrelated HLA matched donor marrow transplantation in treatment of myelodysplastic syndrome, one case (male, 31 years old) of myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) has been received unrelated HLA-matched donor transplantation. Busulfan, cyclophosphamide, Ara-C, MeCCNU and antithymocyte globulin (ATG) were used for preparative regimen. Mycophenolate mofetile, cyclosporin A and short-term methotrexate were used for graft-versus-host disease prophylaxis. The results showed that neutrophil of > 0.5 x 10(9)/L, platelet of 58 x 10(9)/L and hemoglobin of 114 g/L were observed at 10, 20 days and 3 months respectively post transplantation. Disease-free survival without GVHD was 9 months. In conclusion, unrelated HLA matched donor marrow transplantation is an effective approach for treatment of patients with MDS.
 ...
PMID:[Unrelated HLA-matched donor marrow transplantation for one case of myelodysplastic syndrome]. 1522 72

Busulfan (Bu)-based preparative regimens have not been extensively investigated in Hodgkin disease (HD). The purposes of this study were to investigate the toxicity and efficacy of a novel preparative regimen of Bu 14 mg/kg, etoposide 50-60 mg/kg, and cyclophosphamide 120 mg/kg in patients with primary refractory and relapsed HD. One hundred twenty-seven patients with a median age of 33 years (range, 14-67 years) underwent transplantation. The regimen was well tolerated, with 5.5% treatment-related mortality at 100 days after transplantation. With a median follow up of 6.7 years, the 5-year progression-free survival was 48 +/- 5%, and the 5-year overall survival was 51 +/- 5%. A Cox proportional hazards model identified refractory disease at time of transplantation as the only significant factor affecting relapse and overall survival, whereas disease bulk >10 cm affected overall survival. Five patients died between 5.3 and 9.3 years of late complications, including secondary myelodysplasia or acute myeloid leukemia, secondary solid malignancies, and pulmonary toxicity. This novel Bu regimen is comparable to other radiation-free preparative regimens in its effectiveness in the control of HD and with a low-risk of early treatment-related mortality.
 ...
PMID:Long-term outcome of Hodgkin disease patients following high-dose busulfan, etoposide, cyclophosphamide, and autologous stem cell transplantation. 1753 85


1 2 Next >>