Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of BMT from an unrelated donor (MUD) in a patient affected by Wiskott- Aldrich syndrome (WAS). The donor-recipient pair was completely identical for two HLA-extended haplotypes. The conditioning regimen consisted of Bu 14 mg/kg followed by CY 200 mg/kg. GVHD prophylaxis was carried out with CsA plus short-term MTX. Allogeneic engraftment was obtained without any signs of acute or chronic GVHD. At fifteen months from the transplant the patient was in an excellent clinical condition. This case confirms the role of BMT from MUD in WAS, and suggests that complete donor-recipient identity for two entire HLA-extended haplotypes is a particularly favorable immunogenetical condition in this type of transplant.
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PMID:Unrelated bone marrow transplantation in a Wiskott-Aldrich syndrome patient sharing two HLA-extended haplotypes with the donor. 864 53

To assess feasibility and potential advantages of PBSC allograft, we transplanted nine patients (age 20-47 years) with advanced or poor-risk hematologic malignancies. These included eight HLA-identical sibling transplants and one partially matched. Cells were collected from donors by apheresis after rh-G-CSF 10-16 micrograms/kg/day for 4-5 days, and stored at 4 degrees C until infusion. Patients were conditioned with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg, and received GVHD prophylaxis with CSA-MTX. The graft consisted of PBSC alone, with a median of 101.2 (range 28-254.2) x 10(4)/kg CFU-GM, 6.84 (range 4.57-15.9) x 10(6)/kg CD34+ cells and 2.5 (range 1.2-6) x 10(8)/kg CD3+ cells. An ANC > 0.5 x 10(9)/1 occurred on (median) day 13 range 11-17), and a platelet count > 50 x 10(9)/l on (median) day 15 (range 12-29) post graft. One patient died of ARDS on day 13, the others are alive 96-485 (median 245) days from the graft. Two patients have relapsed, one of them with isolated CNS involvement. Acute GVHD (grade I-II) occurred in three patients and severe chronic GVHD in six patients, with no relationship to CSA withdrawal. This unexpected incidence of chronic GVHD might be linked to the high number of CD3+ cells in the graft, contributing to a favourable GVL effect.
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PMID:High incidence of chronic GVHD after primary allogeneic peripheral blood stem cell transplantation in patients with hematologic malignancies. 872 54

We analysed 35 risk factors for acute GVHD in 291 consecutive recipients of HLA-identical sibling marrow transplants from 1975 to 1993. Of these, 16% developed moderate-to-severe acute GVHD following transplantation. In multivariate analysis, GVHD prophylaxis with monotherapy (MTX or CsA) (P = 0.015) seropositivity for several herpes viruses in the donor (P = 0.015) and seropositivity for CMV in the recipient (P = 0.037) before the transplants as well as early engraftment (P = 0.016), were the principal risk factors for GVHD. A high serum TNF-alpha level during conditioning therapy was also a significant risk factor in 75 recipients (P = 0.005). The risk of grades II-IV acute GVHD increased with the number of risk factors. Thus the cumulative incidence of acute GVHD was 1%, if no risk factor was present, 4% with one, 9% with two, 21% with three and 44% in patients with four risk factors. Factors reported to correlate with acute GVHD, such as age, diagnosis, female donor to male recipient, relative response and donor-responding capacity in MLC, MNS blood group antigen, splenectomy and bone marrow cell dose were not associated with acute GVHD in this study. Five-year survival was 24% in patients with grades II-IV GVHD vs 62% in patients with grades 0-I GVHD (P = 0.0001).
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PMID:Risk factors for acute graft-versus-host disease in 291 consecutive HLA-identical bone marrow transplant recipients. 875 Feb 64

An 8-year-old boy with combined IgG1 deficiency and neutropenia underwent allogeneic BMT from his HLA-identical, MLC-negative sister, because immunoglobulin (Ig) infusions and prophylactic antibiotics failed to prevent life-threatening infections. Conditioning was with busulfan and cyclophosphamide, MTX and CYA were given for the prophylaxis of GVHD. For 16 months after BMT no serious infections have occurred and serum IgG1 levels have returned to the normal range without Ig replacement. BMT may be appropriate treatment for patients with IgG subclass deficiency who rarely respond to conservative therapy.
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PMID:Successful bone marrow transplantation in a child with combined IgG subclass deficiency and neutropenia. 875 Feb 81

Allogeneic BMT provides the best treatment currently available for long-term disease-free survival in patients with recurrent ALL. Historically, partially matched related donors provided the opportunity for treatment to a greater number of patients than matched related donors at the expense of decreased overall survival. In this study we compare the results in recurrent ALL patients transplanted with either HLA identical sibling bone marrow or partially matched related bone marrow. Thirty-two patients with relapsed ALL received partially matched bone marrows from a relative with one to three HLA, A, B and Dr antigen mismatches. Bone marrow was partially T cell-depleted with murine T10B9.1A-31 moAb. Sixteen patients with relapsed ALL received HLA-matched sibling bone marrows. All partially matched patients received additional GVHD prophylaxis with methylprednisolone in addition to anti-CD5 immunotoxin and/or CYA. All matched patients in addition to methylprednisolone received MTX and/or CYA. We observed no difference in disease-free survival between patients transplanted with partially matched bone marrow (median follow-up 1252 days, range 778-2035 days) vs those transplanted with HLA-matched bone marrow (median follow-up 1472 days, range 1165-2800 days; P = 0.48). Median survival for all patients is 38% (95% CI 24-52%) at 6 years. Patients transplanted in remission had a significant increase in disease-free survival when compared to those in relapse (P = 0.007). Our data suggest that partially matched BMTs from related donors are a comparable alternative to fully matched transplants in patients with ALL.
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PMID:Allogeneic bone marrow transplantation with T cell-depleted partially matched related donors for advanced acute lymphoblastic leukemia in children and adults: a comparative matched cohort study. 880 94

Allogeneic BMT is the treatment of choice for patients with SAA who have an HLA-identical sibling donor. The results, however, have been relatively poor for transplants from partially matched family donors or unrelated donors because of the high incidence of graft rejection and/or GVHD. Six multiply transfused patients received a novel conditioning regimen of CY 200 mg/kg and TBI 800 cGy prior to receiving marrow from their HLA-haploidentical family donors. Three recipient-donor pairs were mismatched for one HLA locus, one for two loci and two for three loci. A combination of MTX and CsA was used for GVHD prophylaxis. Engraftment was noted in all six patients. Acute GVHD occurred in four patients, two each for grade I and II, respectively. One patient, who was ABO-compatible with her donor had delayed onset of pure red cell aplasia (PRCA) which completely recovered 6 months after additional immunotherapy with prednisolone. There were two deaths; both occurred while patients were on treatment for GVHD. One was from systemic fungemia and the other probably from cytomegalovirus interstitial pneumonitis (CMV-IP). Four patients (66.7%) have been alive and disease-free for more than 8.2, 27.3, 38.4 and 47.2 months after BMT, respectively. The results suggest that CY/TBI-800 may be a simple and effective conditioning regimen for SAA patients receiving BMT from family members other than HLA-identical siblings.
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PMID:CY/TBI-800 as a pretransplant regimen for allogeneic bone marrow transplantation for severe aplastic anemia using HLA-haploidentical family donors. 886 34

A 44-year-old woman with Ph-positive CML was treated with TBI, splenic irradiation, Ara-C, and CY. She then received unmanipulated marrow cells from her HLA-identical brother. GVHD prophylaxis was FK506 and MTX. WBC counts reached 1000/microliter on day 28 when all metaphases of marrow cells showed 46XY. However, on day 42, 46XX was detected in two of 20 metaphases, and the percentage of cells with female karyotype subsequently increased. On day 519, all metaphases showed female karyotype. BCR-ABL mRNA and Philadelphia chromosome were never detected throughout her post-transplant course. Fluorescence in situ hybridization (FISH) revealed complete recovery of host-derived hematopoiesis in the bone marrow, however, mixed T cell chimerism in the peripheral blood. This suggests that the persistence of donor-derived T cells may prevent disease recurrence through graft-versus-leukemia effect. The patient remains in a molecular complete remission with host-derived hematopoiesis 749 days post-transplant.
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PMID:Durable molecular remission in a patient with chronic myelogenous leukemia and host-derived hematopoiesis after allogeneic bone marrow transplantation. 889 99

An increasing number of volunteer unrelated donor bone marrow transplantations (VUD-BMT) are performed every year for hematological malignancies due to the availability of a large donor pool. Here we show the results of 36 VUD transplants from our institution using a chemotherapy-only conditioning regimen comprising busulfan 4 x 4 mg/kg and cyclophosphamide 2 x 60 mg/kg. All patients received heparin 200 IU/kg bw continuous i.v. infusion starting the day before conditioning until day +30. Thirty-four of 36 patients (94%) engrafted and no secondary graft failure was observed. The two non-engraftments occurred in patients with CML in blast crisis with extensive myelofibrosis. All 34 engrafted patients (100%) were in complete remission on day +30 as shown by bone marrow biopsy and cytogenetic examinations. No life-threatening treatment-related morbidity or mortality (TRM) were observed, in particular, no severe veno-occlusive disease (VOD) of the liver and no fatal pulmonary complication. Use of G-CSF significantly shortened the time of neutropenia by 5 days. GVHD prophylaxis consisted of CsA/methylprednisolone with or without MTX. Acute GVHD grade II-IV was observed in 18/34 patients (53%) and cGVHD in 12/27 patients (45%), who survived to day +100. In seven patients (four with HLA class I or II mismatch) anti-T-lymphocyte globulin (ATG) was added for acute GVHD prophylaxis. One of seven had aGVHD grade II and none developed grade III to IV GVHD or graft failure. We conclude that Bu/CY is a feasible, save and sufficiently immunosuppressive regimen for VUD transplantation. Severe acute GVHD might be avoided by additional use of ATG in GVHD prophylaxis.
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PMID:Busulfan/cyclophosphamide in volunteer unrelated donor (VUD) BMT: excellent feasibility and low incidence of treatment-related toxicity. 920 9

We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients transplanted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59 from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31 +/- 3%. In univariate analysis, five variables had a favorable effect on LFS: transplant in first chronic phase (P = 0.0001), time interval from diagnosis to BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P + 0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P = 0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8% in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%, respectively. This suggests that the long-term outcome of patients with favorable prognostic features can approach that of patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not justifiable for these individuals.
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PMID:European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 923 50

A 37-year-old female highly alloimmunized by multiple transfusions received a sex matched HLA-identical unrelated bone marrow transplant for hypoplastic MDS-RA with moderate myelofibrosis. Conditioning consisted of total body irradiation, cyclophosphamide and ATG, GVHD prophylaxis consisted of CsA, MTX and prednisolone. The CD34+ stem cell content of the first graft was relatively low due to an inadequate harvest. The patient appeared not to have engrafted by day 23 post-BMT. She therefore received a second sex mismatched HLA-identical unrelated bone marrow graft on day 25 after two days of 3.5 mg/kg methylprednisolone from a different donor. Over the ensuing days, the first marrow showed slow engraftment followed by engraftment of the second graft. The first graft was then rejected, as monitored by peripheral blood studies of chimerism. No signs of acute GVHD were observed. Despite successful trilineage engraftment and complete second donor chimerism, the patient died from disseminated toxoplasmosis encephalitis and pneumonia on day +104.
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PMID:Second unrelated bone marrow transplantation without additional conditioning therapy after engraftment failure. 948 60


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