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)

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but serious complication of blood component therapy in patients with haematological malignancies. B-chronic lymphocytic leukaemia (B-CLL), however, has rarely been associated with TA-GVHD. We report three patients with advanced B-CLL who developed TA-GVHD. All these had been treated with fludarabine. Suppression of T cells by fludarabine may have contributed to an increased susceptibility to TA-GVHD. The use of irradiated blood products to prevent this complication should be considered for patients with advanced B-CLL treated with fludarabine or other purine analogues.
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PMID:Transfusion-associated graft-versus-host disease in fludarabine-treated B-chronic lymphocytic leukaemia. 781 85

Unusually severe infections phenomena were observed in three patients with chronic lymphocytic leukemia (CLL) who had undergone allogeneic bone marrow transplantation (BMT) from matched sibling donors. The first developed three episodes of cytomegaloviremia requiring anti-viral therapy; the third episode accompanied by cytomegalovirus hepatitis which required prolonged therapy with foscarnet. Another had Listeria monocytogenes meningitis which was difficult to eradicate and required prolonged maintenance antimicrobial therapy with oral trimethoprim-sulfamethoxazole and intrathecal gentamicin until death due to chronic graft-versus-host disease. The third patient had cytomegaloviremia lasting 47 days, which did not clear within 4 weeks of full-dose ganciclovir. Although the number of patients is small, in our experience the problems encountered were unusually severe compared with patients allografted for other disease. We conclude that CLL patients undergoing allogeneic BMT may be at a higher risk of infectious complications than patients allografted for other diseases, and require careful monitoring.
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PMID:Unusual infections following allogeneic bone marrow transplantation for chronic lymphocytic leukemia. 788 13

Transfusion-associated graft-versus-host disease (TA-GVHD), has rarely been reported associated with B-chronic lymphocytic leukaemia (B-CLL). We report a patient diagnosed with B-CLL, previously treated with fludarabine, who developed TA-GVHD after being transfused during surgery for splenectomy. Diagnosis was confirmed by polymerase chain reaction (PCR) detection of donor DNA in the patient, by amplification of Y-chromosome sequence and analysis of minisatellite polymorphisms. B-CLL patients treated with fludarabine appear to be at risk for TA-GVHD and should be regarded as candidates for transfusions with irradiated blood products. This case illustrates that PCR is a rapid technique for the early diagnosis of TA-GVHD.
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PMID:Diagnosis of transfusion-associated graft-versus-host disease by polymerase chain reaction in fludarabine-treated B-chronic lymphocytic leukaemia. 865 6

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

One patient with refractory B cell chronic lymphocytic leukemia (CLL) and another with refractory B cell prolymphocytic leukemia (PLL) underwent bone marrow transplantation (BMT) from HLA-identical siblings. Circulating malignant cells persisted at high levels in the patient with PLL and there was clinical evidence of disease progression soon after transplant in the patient with CLL. Starting 4-5 weeks post-BMT, cyclosporine was tapered rapidly to stimulate immunologic graft-versus-leukemia (GVL) reactions. There was a fall in the number of malignant cells and reversal of organomegaly with the onset of acute graft-versus-host disease (GVHD). Both patients received conventional doses of corticosteroids for GVHD which also may have contributed to disease response to some extent. Total clearance of the leukemic cells from the peripheral blood was seen in both patients, and clearance of the marrow was seen in the patient with CLL. However, both patients died of complications of severe GVHD. We conclude that GVHD may be associated with a GVL effect after allogeneic BMT for refractory chronic B cell lymphoproliferative diseases. Whether GVL reaction occur in the absence of clinically obvious GVHD after allogeneic BMT for CLL remains to be seen.
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PMID:Clinical and hematologic response of chronic lymphocytic and prolymphocytic leukemia persisting after allogeneic bone marrow transplantation with the onset of acute graft-versus-host disease: possible role of graft-versus-leukemia. 870 89

A 49-year-old man with a 3-year history of chronic lymphocytic leukemia (CLL, stage B at diagnosis) responded well to four course of fludarabine, but developed marrow failure and prolonged pancytopenia lasting 9 months following the fifth course. Fludarabine therapy could not be continued due to pancytopenia, eventually resulting in disease progression. Bone marrow transplantation from an unrelated donor mismatched at one DRB1 locus and both DQB1 loci was performed as salvage therapy. The marrow was depleted of T cells with Campath-1G. Pre-transplant immunosuppression was enhanced with 600 cGy total lymphoid irradiation and Campath-1G infusions in addition to 120 mg/kg cyclophosphamide and 1200 cGy fractionated total body irradiation. Cyclosporine alone was used as post-transplant immunosuppression. Neutrophils reached 0.5x10(9)/1 on day 14 and platelets 50 x 10(9)/1 on day 40. No acute graft-versus-host disease was seen. Bulk disease detected on CT scanning prior to BMT was found to have disappeared 10 weeks after BMT. The marrow showed residual disease (5% CD5+/CD19+ cells) 9 weeks after transplantation, which had decreased markedly at 13 (0.5%) and 26 (0.4%) weeks. The patient is currently alive and well 10 months after BMT with no clinically detectable disease. We conclude that BMT from an unrelated donor is a feasible treatment option in advanced CLL.
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PMID:T cell-depleted allogeneic bone marrow transplantation from a partially HLA-mismatched unrelated donor for progressive chronic lymphocytic leukemia and fludarabine-induced bone marrow failure. 873 15

We report the case of a patient with chronic lymphocytic leukemia (CLL) with persistent lymphocytosis and lymphadenopathy after allogeneic bone marrow transplantation (BMT). After receiving a donor lymphocyte infusion on day 87 he achieved complete remission upon development of chronic graft-versus-host disease, suggesting that a graft-versus-leukemia effect is operative in this malignancy.
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PMID:Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. 887 40

The absence of an effective therapy for most patients with leukemia who relapse after allogeneic BMT has generated interest in new strategies. We present our experience on the use of filgrastim 5 micrograms/kg/day s.c., in four patients with leukemia (three with AML and one with CLL) who relapsed after allogeneic transplantation. One patient with AML achieved CR after 55 days of treatment. No response was observed in the remaining three. The patient who responded developed extensive chronic GVHD but relapsed 10 months later. In one of the unresponsive patients a dramatic increase in bone marrow infiltration and WBC count followed administration of filgrastim. We conclude that filgrastim can occasionally induce CR in leukemic patients who relapse after BMT.
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PMID:Filgrastim for the treatment of leukemia relapse after bone marrow transplantation. 889 4

The outcome of allogeneic haemopoietic transplants including the rate of immune complications for patients with chronic lymphocytic leukaemia (CLL) refractory to or relapsing after chemotherapy with fludarabine was analysed. Fifteen patients with advanced CLL who received allogeneic transplantation were prospectively analysed. All patients had previously received chemotherapy with fludarabine for 3-15 courses; 12 were refractory. The median number of circulating CD4+ and CD8+ lymphocytes at the time of transplant was 0.49 x 10(9)/l and 0.23 x 10(9)/l, respectively. One patient was transplanted from a one HLA-antigen mismatched unrelated donor. Three others received a one or two antigen mismatched graft and 11 had HLA-identical sibling donors. Patients received cyclosporine or tacrolimus in addition to methotrexate or methylprednisolone for prophylaxis of acute graft-versus-host disease (aGVHD). Fourteen patients engrafted; one patient had graft failure, but recovered after therapy with intravenous immunoglobulin. 13 (87%) achieved complete remission (CR). Nine (53%) remain alive and in CR with a median follow-up of 36 (range 3-60) months. None developed visceral graft-versus-host disease. These data compared favourably to published reports in other leukaemia patients and for patients with CLL who received a comparable immunosuppressive therapy but without prior fludarabine exposure. This data indicates that allogeneic haemopoietic transplantation can induce durable remission in patients with CLL refractory to fludarabine and that it is reasonable to delay transplantation until failure of fludarabine therapy. It also suggests that prior exposure to fludarabine may decrease the incidence of severe aGVHD, possibly through its immunosuppressive effects. Further studies are warranted to evaluate this observation.
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PMID:Allogeneic blood or marrow transplantation for chronic lymphocytic leukaemia: timing of transplantation and potential effect of fludarabine on acute graft-versus-host disease. 916 17

We have prospectively evaluated the feasibility and results of the biotin-avidin immunoadsorption method (Ceprate SC system) for a phase I/II study of T-cell depletion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cells (PBPC) for allogeneic transplantation. Twenty consecutive patients, median age, 40 years (21 to 54) and diagnoses of chronic myeloid leukemia in chronic phase (n = 5), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2), chronic myelomonocytic leukemia (n = 1), refractory anemia with excess of blasts in transformation (n = 3), histiocytosis X (n = 1), and chronic lymphocytic leukemia (n = 1), were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (13 Gy; 4 fractions). HLA identical sibling donors received G-CSF at 10 microg/kg/d subcutaneously (SC); on days 5 and 6 (19 cases) and days 5 to 8 (1 case) donors underwent 10 L leukapheresis. PBPC were purified by positive selection of CD34+ cells using immunoadsorption biotin-avidin method (Ceprate SC) and were infused in the patients as the sole source of progenitor cells. No growth factors were administered posttransplant. The median recovery of CD34+ cells after the procedure was of 65%. The median number of CD34+ cells infused in the patients was 2.9 (range, 1.5 to 8.6) x 10(6)/kg. The median number of CD3+ cells administered was 0.42 x 10(6)/kg (range, 0.1 to 2). All patients engrafted. Neutrophil counts >500 and >1,000/microL were achieved at a median of 14 days (range, 10 to 18) and 15 days (range, 11 to 27), respectively. Likewise, platelet counts >20,000 and >50,000/microL were observed at a median of 10 days (range, 6 to 23) and 17 days (range, 12 to 130), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine plus methylprednisolone. No patient developed either grade II to IV acute or extensive chronic GVHD. After a median follow-up of 7.5 months (range, 2 to 22) three patients have relapsed, and one of them is again in hematologic and cytogenetic remission after infusion of the donor lymphocytes. Two patients died in remission: one on day +109 of pulmonary aspergillosis and the other on day +251 of metastasic relapse of a previous breast cancer. Sixteen of the 20 patients are alive in remission after a median follow-up of 7.5 months (range, 2 to 22). In conclusion, despite the small number of patients and limited follow-up, it appears that this method allows a high CD34+ cell recovery from G-CSF mobilized PBPC and is associated with rapid engraftment without significant GVHD, and with low transplant related mortality.
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PMID:Rapid engraftment without significant graft-versus-host disease after allogeneic transplantation of CD34+ selected cells from peripheral blood. 916 34


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