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)

The best strategies for haploidentical stem cell transplants are not known. We used a standard myeloablative pretransplant conditioning regimen (30 mg/kg VP-16, 120 mg/kg cyclophosphamide, and 12 Gy of TBI in six fractions), an increased peripheral stem cell dose of > 10 x 10(6) CD34+ cells/kg, T cell depletion (with CD34+ cell selection and CD4/CD8 depletion steps) to < 1 x 10(5) CD3+ cells/kg and cyclosporine post transplant. Ten patients (7M/3F, median age 11 (3-33) years) with high-risk leukemia (AML in 4, MDS in 2, CML in 1 and T-ALL in 3) received a hemopoietic stem cell transplant (HSCT) from a haploidentical father or sibling. The median number of CD34+ cells was 12.9 (9.5-45.7) x 10(6) cells/kg; median number of CD3+ cells was 0.41 (0.09-1.89) x 10(5) CD3+ cells/kg. All patients initially achieved 0.5 x 10(9)/l neutrophils at a median 12 (10-21) days. Graft failure in two consecutive patients out of four on the original protocol led to a modification adding ATG pretransplant and OKT3 post transplant. Graft failure was observed in one out of six subsequent patients. Acute GVHD > or = grade II was observed in three patients. Three of 10 patients are alive in CR at > 24 and >3 (2) months after transplant. Seven patients died: four of transplant related complications and three of relapse. Increased stem cell dose (> or = 10 x 10(6) CD34+ cells/kg) as obtained using currently available technology may not be sufficient to ensure stable engraftment in patients with high-risk leukemia using standard myeloablative conditioning regimens.
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PMID:Increased stem cell dose, as obtained using currently available technology, may not be sufficient for engraftment of haploidentical stem cell transplants. 1110 99

Between 1991 and 1999, 44 leukemic patients received donor lymphocyte infusions (DLIs) at our center (22 patients with chronic myelogenous leukemia [CML]; 10 with acute myelogenous leukemia; 11 with acute lymphatic leukemia; and 1 with myelodysplastic syndrome). Seventeen patients received graft-versus-host disease (GVHD) prophylaxis with methotrexate (MTX) at the time of DLI. In CML patients, 15 of 22 (68%) re-entered complete remission after DLI. At 3 years post-DLI, patients with cytogenetic (n = 10) or molecular (n = 3) relapse had a current leukemia-free survival (cLFS) rate of 85% compared with 0% for patients with hematologic relapse (P < .001). Among 15 CML patients who initially responded to DLI, 4 patients relapsed within the first 2 years. Four of 16 patients (25%) with acute leukemia had an initial response with complete remission after DLI. Two of them subsequently relapsed within 1 year. Patients with acute leukemia who relapsed within 1 year of hematopoietic stem cell transplantation (n = 9) had 0% cLFS at 18 months; patients with later relapse had 29% cLFS (P = .015). The overall probability of cLFS at 3 years for CML patients was 46%. For other diseases, cLFS was 13% at 18 months after DLI. Patients who developed chronic GVHD secondary to DLI showed a 3-year cLFS of 51% compared with 18% for patients without chronic GVHD (P = .022). This study emphasizes the importance of early disease stage and presence of chronic GVHD for effective DLI.
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PMID:The role of disease stage in the response to donor lymphocyte infusions as treatment for leukemic relapse. 1121 96

We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 x 107 CD3+ cells, given at 30, 60 and 90 days post-allogeneic blood and marrow transplantation (BMT), following conditioning with fludarabine 30 mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxis consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with life expectancy less than 6 months were studied; none were in remission. Diagnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a median of 450 days (range, 450-540). Two patients are in remission of CML in blast crisis and AML for more than 14 months. Median survival is 116 days (range, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CML in blast crisis went into CR after the first DLI. The overall incidence of acute GVHD was 70%. Primary causes of death were infections (n = 3), acute GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observed high response and chimerism rates at the expense of an excessive incidence of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patients, and its role in this setting remains unclear.
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PMID:Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease. 1124 40

Unrelated donor bone marrow transplant (UD-BMT) has become an attractive alternative source of hematopoietic cells for patients lacking a matched sibling. The aim of this paper was to report on results of the 696 UD BMTs performed in 31 Italian institutions during the first 10 years of activity of the Italian Bone Marrow Donor Registry (IBMDR). In 1989 the Italian Bone Marrow Transplant Group (GITMO) established the IBMDR to facilitate donor search and marrow procurement for patients lacking an HLA identical sibling. By end of December 1999, 260,000 HLA-A, B typed volunteer donors had been cumulatively registered and 2,620 searches had been activated for Italian patients. At least one HLA-A, B, DRB1 matched donor was found for 54% of the patients and 696 UD BMTs were performed. In 50% of cases the donor was found in the IBMDR and in 50% in 15 other Registries. The average time from search activation to transplant was 6 months for disease other than CML. For CML it was 14 months. Actuarial 12-month transplant-related mortality (TRM) was 68% in patients grafted between 1979 and 1992 and 44% for patients grafted after 1993. Twenty-eight per cent of patients developed grade III or IV acute GvHD and 24% developed extensive chronic GvHD. The rate of disease free survival at three years was 57% for patients with 1st chronic phase CML, 37% for patients with 1st or 2nd CR ALL, 31% for AML or MDS patients < or = 18 years of age and 54% for patients with inborn errors. We conclude that the IBMDR has benefited a substantial number of patients lacking a matched sibling and has facilitated the recruitment of UDs into the international donor pool. The long time required for the search is the major obstacle to the success of this programme. This suggests that early transplant and a decrease in TRM could further improve these encouraging results.
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PMID:Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Transplant Group (GITMO). 1126 21

From 1986 to June 2000, sixty children suffering from acute and chronic leukemia (n = 42, 33 of which in resistant relapse), genetic diseases (n = 11), aplastic anemia (n = 2, one of which with platelet refractoriness and bleeding), myelodysplasia (n = 5) received an haploidentical bone marrow, mismatched for 2-3 HLA loci. The donor's marrow was treated in vitro with vincristine and methylprednisolone to obtain a functional T depletion (MLC and CTL inhibition, functional blockade of Th1 and Th2). The prevalence of infectious complications and GVHD was similar to that recorded in matched unrelated donor (MUD) transplants. In situations of high risk of rejection (chronic leukemia, genetic diseases) we infused immediately one half of the harvest and then frozen aliquots from the second week. Of the 25 ALL and 8 AML in resistant relapse, 3 survived, disease-free at 14, 8 and 1 years respectively. Of the 3 ALL, transplanted during remission, 1 is surviving at 18 months. Of the 6 CML, 1 had fractionated bone marrow and is surviving at 3 years, and 5 had standard single dose infusion and died of progression of their disease after rejection of the graft (4) or blast crisis after complete engraftment (1). The 2 patients with aplastic anemia, those with myelodysplasia, and 6 of the 10 with genetic disorders died of transplant-related complications or disease progression. 4 patients with osteopetrosis (n = 2), MLD (n = 1), Wiskott Aldrich dis. (n = 1) survive at 8, 2, 5 and 1.5 years respectively. In patients transplanted with fractionated marrow GVHD > 2nd grade occurred in 15%. Only one patient rejected the graft. Compared with MUD transplantation, mismatched BMT whenever performed in patients in good conditions provides similar outcome and widens the donor availability.
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PMID:Haploidentical bone marrow transplantation in leukemia and genetic diseases. 1126 22

Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34(+) cells influence relapse and event-free survival (EFS) after BMT. The study population consisted of 113 consecutive patients with hematologic malignancies who underwent non-T-cell-depleted BMT from HLA-matched siblings. Sixty-four patients had low-risk diagnoses (ALL/AML CR1, MDS RA/RARS, and CML CP1); 49 patients had high-risk diagnoses (all others). CD34(+) cells, T cells, B cells, natural killer cells, monocytes, and a rare population of CD3(-), CD4(bright) cells in the allografts were measured by flow cytometry. The CD3(-), CD4(bright) cells in bone marrow had the same frequency and phenotype as CD123(bright) type 2 dendritic cell (DC) progenitors, and they differentiated into typical DCs after short-term culture. Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3(+) T cells, CD34(+) hematopoietic cells, and CD4(bright) cells as covariates for EFS, relapse, and nonrelapse mortality. Recipients of larger numbers of CD4(bright) cells had significantly lower EFS, a lower incidence of chronic graft-versus-host disease (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of CD34(+) cells had improved EFS; recipients of fewer CD34(+) cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, the content of donor CD4(bright) cells was associated with decreased cGVHD and graft-versus-leukemia effects in recipients of allogeneic bone marrow transplantation, consistent with a role for donor DCs in determining immune responses after allogeneic BMT.
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PMID:Larger numbers of CD4(bright) dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation. 1134 16

A cytogenetic and/or cytochemical study was performed in 166 individuals with leukemia or related disorders, in two major Costa Rican hospitals. In those patients treated at an adult's hospital (14 years old and over), acute leukemias represented 66% of all cases. In that hospital the most frequent types of disorders were, in decreasing order: ANLL (> M1), ALL, CML (all of them showed the Ph chromosome) and MDS. In the cases from a childrens' hospital (< 14 years old) acute leukemias were 98%. Among them the order of frequency was: ALL (70%): ALL-1 (84%), ALL-2 (16%) and ANLL (27%): M5a > M3 > M4 > M5b. In ALL 85% were type B and occurred mostly in women while 15% of them were type T and more frequent in males. There was 5.6% infant leukemia, which presented a similar number of acute lymphoids and myeloids. The cytogenetic pattern was similar among Costa Rica and other tropical and temperate countries.
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PMID:[Cytogenetics and cytochemistry of leukemia patients in 2 neotropical hospitals]. 1135 79

We describe our experience of setting up an allogeneic BMT program at the Christian Medical College Hospital, Vellore over a period of 13 years, from October 1986 to December 1999. Two hundred and twenty-one transplants were performed during this period in 214 patients, with seven patients undergoing second transplants. Indication for BMT were thalassemia major - 106 (48%), CML - 30, AML - 35, ALL - 10, SAA - 22, MDS - six and six for other miscellaneous disorders. The mean age of this patient cohort was 15.6 years (range 2-52). Graft-versus-host disease of grades III and IV was seen in 36 patients (17%) and this was the primary cause of death in 20 patients (9.2%). All patients and donors were CMV IgG positive. Sepsis was the primary cause of death in 16 patients (7.4%), 10 bacterial, four fungal and two viral. One hundred and ten of this series of patients are alive and disease free (50%) with a median follow-up of 24 months (range 2-116). These results are comparable to those achieved for patients with similar disease status in transplant units in the Western world and cost a mean of US$15 000.
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PMID:Allogeneic bone marrow transplantation in the developing world: experience from a center in India. 1147 34

The AML1 (CBFA2) gene is the most frequent target of chromosomal rearrangements observed in human acute leukemia. These rearrangements include the commonly reported t(8;21)(q22;q22) or AML1/ETO fusion in AML-M2, the t(3;21)(q26;q22) or AML1 fusion with one of three genes, MDS1, EAP or EVI1, in therapy-related AML and MDS, as well as in blast crisis in CML and the t(12;21)(p13;q22) or TEL/AML1 fusion in B-cell ALL. In addition to the t(3;21), other AML1 translocations have also been reported in therapy-related MDS and AML, particularly after treatment with topoisomerase II inhibitors. AML1 gene rearrangements have also been observed less frequently with numerous other chromosomal partners. Here, we describe a patient with AML-M4 and a previously unreported rearrangement involving the AML1 locus and an unknown locus on the short arm of chromosome 1 at 1p32.
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PMID:A unique AML1 (CBF2A) rearrangement, t(1;21)(p32;q22), observed in a patient with acute myelomonocytic leukemia. 1156 47

An allogeneic transplantation of CD34(+)-selected cells from peripheral blood (allo-PBT/CD34(+)) from HLA-identical sibling donors was performed in 50 adult patients with acute myeloid leukemia in first complete remission (AML CR1) (n = 29), myelodysplastic syndrome (MDS) (n = 4), or chronic myeloid leukemia in first chronic phase (CML CP1) (n = 17). Clinical results were compared to a concurrent group of 50 patients transplanted with unmodified peripheral blood progenitor cells (allo-PBT), matched for age, diagnosis, and disease stage. The median follow-up period was 29 months (range 1-69). The actuarial probability of developing acute GVHD clinical grade II to IV was 16% (95%CI: 6-26) for the allo-PBT/CD34(+) group and 41% (95%CI: 29-57) for the allo-PBT group (P = 0.002). The actuarial probability of developing extensive chronic GVHD was 22% (95%CI: 8-36) for the allo-PBT/CD34(+) group and 47% (95%CI: 31-63) for the allo-PBT group (P = 0.02). Recipients of allo-PBT/CD34(+) had less toxicity associated with the transplant and better Karnofsky index at the last follow-up. For AML/MDS patients, the actuarial probability of disease-free survival (DFS) for recipients of allo-PBT/CD34(+) and allo-PBT was 65% (95%CI: 45-85) vs43% (95%CI: 28-58) (P = 0.05), respectively. These data provide a rationale for a randomised trial of allo-PBT/CD34(+) vs allo-PBT in AML/MDS patients in early stage of the disease.
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PMID:Allogeneic transplantation of CD34+-selected cells from peripheral blood in patients with myeloid malignancies in early phase: a case control comparison with unmodified peripheral blood transplantation. 1157 6


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