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)

Mantle cell lymphoma (MCL) is a distinctive clinicopathologic entity and represents 2-8% of all non-Hodgkin's lymphomas. The median survival of patients with MCL is only 3 years, and none of the available conventional chemotherapy regimens appears curative. Encouraging results have been reported with high-dose chemotherapy with autologous stem-cell transplantation (autoSCT). However, a plateau in disease-free survival was not observed in relapsed MCL on the autoSCT trials. Promisingly, alloSCT appears to induce durable remissions via a graft-versus-lymphoma (GVL) effect. Donor lymphocyte infusions (DLIs), by virtue of a GVL effect, have been shown to induce durable remissions in a few cases with refractory MCL that recur after alloSCT. In this article, we review the literature on the evidence of the GVL effects in MCL and describe a patient with relapsed MCL shortly after high-dose chemotherapy with autoSCT. The patient was then successfully treated with Bu/Cy/VP-16 for an alloSCT followed by DLIs in a stepwise fashion. MNCs > 10 x 10(8)/kg were collected by two large-volume leukaphereses from the donor. Harvested stem cells from the 2(nd) day were cryopreserved for the future use as prophylactic DLIs to be given in a stepwise fashion. Cyclosporin and methotrexate were used for GVHD prophylaxis. He had achieved only a partial response by D+64 post transplant. G-CSF-primed cryopreserved DLIs were then infused on D+64 and D+92 to enhance the GVL effect. Grade 3 intestinal GVHD developed 20 days after the 2(nd) DLI and was partially controlled with the combination of cyclosporin, prednisone, and mycophenolate mofetil. Clinical complete remission was observed at D+112, and maintained until the last follow-up day (D+615). Our findings suggest that alloSCT followed by prophylactic DLIs may offer a curative approach to refractory MCL.
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PMID:Successful allogeneic stem-cell transplantation with prophylactic stepwise G-CSF primed-DLIs for relapse after autologous transplantation in mantle cell lymphoma: a case report and literature review on the evidence of GVL effects in MCL. 1093 69

Fifty three patients (pts) received an allogeneic hematopoietic transplant using peripheral blood progenitor cells (PBPC). Diagnosis were acute myeloid leukemia (AML) in 16 pts, acute lymphoblastic leukemia (ALL) in 15, chronic myeloid leukemia (CML) in first chronic phase in 12, aplastic anemia in 4, myelodysplasia in 3 and Hodgkin's disease, major thalasemia and Hunter's syndrome in one each. Mean age was 20 years-old (2-55), 28 males and 25 females. Conditioning regimens were total body irradiation with 1200 cGy and cyclophosphamide 120 mg/kg in 38 pts, busulfan 16 mg/kg and cyclophosphamide 120 mg/kg in 10 pts, total lymphoid irradiation and cyclophosphamide in 3, 2 pts received other chemotherapy based conditionings. PBPC were infused unmanipulated through a central catheter. Graft versus host disease (GVHD) prophylaxis was cyclosporin and short course methotrexate. Donors were 6/6 HLA compatible siblings in 52 cases and 5/6 match in one case. PBPC mobilization was done with G-CSF at a dose of 10 micrograms/kg/day subcutaneously for four days, pheresis started on day 5. Bone marrow harvest was also done in the first thirty cases. Mean cellularities for CD34, CD3, CD4, CD8, CD56, CD19 (cel x 10(6)/kg) were 4.12; 4.59; 2.57; 1.9; 0.55 and 0.68, respectively. Mean recovery of neutrophils > 500/microL was obtained on day +11 and platelets > 20,000/microL on day +13. Patients were hospitalized for a mean period of 26 days (range 18-39) and days with parenteral antibiotics were 12.2 (5-45). Two pts had venoocclusive disease of the liver. Transplant related mortality was 15%. Acute graft versus host disease (GVHD) was observed in 43.4% of pts, only 5 pts had acute GVHD III or IV. Mean time for aGVHD diagnosis was +23 (8-76). Forty three pts were evaluable for chronic GVHD with a mean follow-up of 18 months (4-39). Chronic GVHD was observed in 26.4% by day +240, only 2 pts developed severe cGVHD. The present experience demonstrates an acceptable incidence for cGVHD; however, taking into account recent reports showing an increase of this complication, it seems reasonable not to perform this procedure for non-malignant diseases in which graft versus malignancy effect is not to be expected.
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PMID:[Allogeneic hematopoietic transplantation with stem cells extracted from peripheral blood]. 1096 6

For more than 30 yrs allogeneic hematopoietic stem cell transplantations have been successfully performed in patients with hematologic malignancies and bone marrow aplasia. Over the years the field of transplantation has changed dramatically. More and more unrelated donors became available, regimens for haploidentical transplantations were introduced and G-CSF mobilized peripheral blood stem cells and fetal cells from umbilical cord became available as alternate sources of hematopoietic stem cells. However, especially the introduction of donor lymphocyte infusions (DLI) for the successful treatment of leukemic relapses after allogeneic stem cell transplantations improved our understanding of transplantation immunology and opened amazing perspectives in allogeneic transplantation. It was long believed, that myeloablative therapy with high-dose chemotherapy and total body irradiation (TBI) are the sole antileukemic principles in allogeneic transplantations. But by now it became clear, that donor lymphocytes exert a very potent antileukemic effect, now referred as the graft-versus-leukemia (GVL) or graft-versus-malignancy (GVM) reaction. The efficacy of DLI in controlling leukemic relapses suggests that myeloablative therapy is not essential for long-term disease control. By exploiting the GVL or GVM reaction more intensively the role of chemotherapy and TBI is changing to immunosuppression. Sufficient immunosuppression to allow grafting, however, can be achieved with much lower doses as those which have been used in conventional transplants. Therefore allogeneic transplants have become also available for the elderly or for patients with concurrent medical conditions, which would have excluded them from conventional transplants. Moreover, this allogeneic transplantation strategy with reduced intensity conditioning is now also under investigation in patients with susceptible solid tumors and autoimmune diseases. However, one major obstacle in allogeneic transplantations, namely the graft-versus-host disease (GVHD), remains to be solved.
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PMID:Adoptive allogeneic immunotherapy--history and future perspectives. 1103 75

Hematopoietic colony-stimulating factors (CSF) decrease the duration of neutropenia following stem cell transplantation (SCT). With CSF-mobilized allogeneic blood SCT (alloBSCT), the yields of CD34+ cells are several-fold higher than in other SCT settings, raising concern that post-transplant CSF use may be unnecessary. In this study, we estimate the resource and cost implications associated with CSF use following alloBSCT. A cost identification analysis was conducted for 44 patients on a randomized, double-blind placebo-controlled trial of G-CSF following alloBSCT. Study drug was given daily until an absolute neutrophil count (ANC) > or = 1000 cells/microl. Billing information from the time of transplant to day +100 was analyzed. The median number of days to an ANC > or = 500 cells/microl was shorter in the G-CSF arm, 10.5 days vs 15 days (P < 0.001), while platelet recovery and rates of acute graft-versus-host disease (GVHD) and survival were similar. Resource use was similar, including days hospitalized, days on antibiotics, blood products transfused and outpatient visits. Total median post-transplant costs were $76577 for G-CSF patients and $78799 for placebo patients (P = 0.93). G-CSF following allogeneic blood SCT decreased the median duration of absolute neutropenia and did not incur additional costs, but did not result in shorter hospitalizations, or less frequent antibiotic use.
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PMID:Economic analysis of a phase III study of G-CSF vs placebo following allogeneic blood stem cell transplantation. 1104 69

We performed a case-control analysis of 42 patients with advanced leukemia or MDS comparing peripheral blood stem cell (PBSC) with marrow grafts (BMT) from HLA-matched sibling donors. PBSC were mobilized with G-CSF (7.5 microg/kg/day) and yielded a median of 6.7 x 10(6) CD34+ cells/kg (range, 1.6-15.0) and 2.7 x 10(8) CD3+ cells/kg (range, 1.1-7.1) vs marrow grafts with a median of 2.0 x 10(8) nucleated cells/kg (range, 1.8-2.2). Recovery was significantly faster after PBSCT compared to BMT, with a median of 17 (range, 12-26) vs 26 (range, 16-36) days, respectively, to neutrophils >0.5 x 10(9)/l (P < 0.01), and 22 (range, 12->60) vs 42 (range, 18->60) days, for platelet recovery (P < 0.01). Transplantation of >/=7 x 10(6) CD34+ cells/kg accelerated recovery to >20 x 10(9) l platelets; median 17 days (range, 12-19) vs 23 days (range, 17-36) for those receiving <7 x 10(6)/kg (P = 0.01). PBSC and marrow recipients had similar risks of grades II-IV or III-IV acute GVHD or extensive chronic GVHD (all P > 0.3). At 1 year after PBSCT and BMT, the risk of relapse was 41% and 32%, respectively (P = 0.47), and the probability of survival was 46% and 48%, respectively (P = 0.70). HLA-matched sibling PBSCT resulted in faster neutrophil and platelet engraftment compared to BMT, with no subsequent differences in acute or chronic GVHD, relapse or survival. A minimum of 7 x 10(6) CD34+ cells/kg in PBSC grafts may be required for very rapid platelet engraftment. Bone Marrow Transplantation (2000) 26, 723-728.
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PMID:Matched-pair analysis of peripheral blood stem cells compared to marrow for allogeneic transplantation. 1104 52

The feasibility of transplantation using highly purified G-CSF-mobilized peripheral blood CD34+ cells from HLA-identical sibling donors without prophylactic post-transplant immunosuppression was prospectively studied in 10 adult first chronic phase chronic myeloid leukemia (CML) patients with special reference to graft engineering performance and follow-up studies of minimal residual disease and immune reconstitution. CD34+ cells were enriched by clinical-scale magnetic-activated cell separation (MACS) using iron-dextran beads bound to monoclonal anti-CD34 antibody. Grafts contained a median of 9.7 (range 1.7-16.6) x 10(6) CD34+ cells per kilogram of recipient body weight with a purity between 94.5% and 98.3% (median 97.2%). The median number of transfused CD3+ T lymphocytes was 1.0 (range 0.5-8.5) x 10(4)/kg, corresponding to a log10 T lymphocyte depletion between 3.8 and 5.0 (median 4.6). All patients engrafted rapidly with a median duration to neutrophil counts >500/microl of 8 (range 8-19) days and to self-sustaining platelet counts >20,000/microl of 12 (range 9-25) days. Isolated skin acute graft-versus-host disease (GVHD) of stages I to II occurred in three patients. One patient developed secondary graft failure and was successfully salvaged by an unmanipulated blood stem cell graft from the same donor. All 10 patients are surviving in complete hematologic, cytogenetic and molecular remission (four patients after donor lymphocyte infusions) between 12 and 22 (median 16) months post transplant. In conclusion, transplantation of MACS-purified blood CD34+ cells from HLA-identical sibling donors in adult CML patients appears safe, effectively prevents acute GVHD without prophylactic post-transplant immunosuppression, and is capable of inducing complete cytogenetic and molecular remissions.
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PMID:Transplantation of highly purified HLA-identical sibling donor peripheral blood CD34+ cells without prophylactic post-transplant immunosuppression in adult patients with first chronic phase chronic myeloid leukemia: results of a phase II study. 1108 80

After myeloablative treatment and allogeneic stem cell transplantation (ASCT), patients are kept isolated in the hospital to prevent infections during neutropenia. To date, 22 patients have been given the choice of being treated at home. Eleven could not be treated at home, and they served as controls. Most had haematological malignancies. The donors were 12 HLA-compatible unrelated, nine HLA-identical siblings and one twin. In the home care group, three developed bacteraemia, compared to nine in the controls (P < 0.01). Patients in the home care group had fewer days of total parenteral nutrition (median 3 vs 24, P < 0.001), required fewer erythrocyte transfusions (median 4 vs 8, P = 0.01), fewer days on i.v. antibiotics (median 6 vs 13 days), and on analgesics (median 0 vs 15) than the controls (P < 0.05). Days with fever, time to engraftment, days with G-CSF and acute GVHD were the same in the two groups. Seven of 11 patients treated at home were readmitted to the ward for a median of 3 (0-7) days, due to fever or lack of a caregiver at home. Days to discharge to the out-patient clinic were faster in the group treated at home (median 20 vs 35 days, P < 0.01). Patients who were treated at home enjoyed being active and taking a walk when they felt like it. This preliminary report suggests that home care after ASCT is not only safe, but superior to isolation in the hospital.
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PMID:Is it safe to treat allogeneic stem cell transplant recipients at home during the pancytopenic phase? A pilot trial. 1110 3

A 15-year-old female received an unrelated three of six HLA antigen matched umbilical cord blood (UCB) transplant for refractory, relapsed T-cell ALL. Conditioning consisted of TBI, melphalan, and anti-thymocyte globulin (ATG), with cyclosporin A (CsA) and solumedrol for GVHD prophylaxis. She engrafted and a day 34 bone marrow aspirate showed 100% donor cells and no evidence of leukemia. The post-transplant course was complicated by mild grade I acute GVHD involving skin, and limited chronic GVHD of the gut which resolved with the addition of 1 mg/kg/day of steroids to her CsA prophylaxis. One hundred and ninety days after transplantation the patient developed pancytopenia and was subsequently found to have a leukemic relapse. Immunosuppression was discontinued and she was started on G-CSF and erythropoietin. Moderate skin and gut GVHD developed which was treated with both topical and low-dose oral steroids. Over the next few weeks she became transfusion independent and a follow-up bone marrow aspirate showed complete remission. She continued in complete remission for 4 months, at which time localized leukemic relapse was found in a soft tissue breast mass in spite of continued bone marrow remission. While the patient ultimately died of progressive disease, this case demonstrates that mismatched UCB in conjunction with G-CSF is capable of generating a GVL effect that can induce a complete remission.
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PMID:Graft-versus-leukemia-induced complete remission following unrelated umbilical cord blood transplantation for acute leukemia. 1114 43

Donor leukocyte infusions are an effective therapy for patients who relapse with leukemia after bone marrow transplantation. We report the case of 14-year-old boy who relapsed 34 months after sibling donor bone marrow transplant for Philadelphia-positive chronic myeloid leukemia. Subsequently, he received three infusions of donor mononuclear cells (DMNC) harvested in steady state hematopoiesis and one G-CSF mobilized-peripheral blood mononuclear cells (PBMC) infusion. Simultaneously, test named as--"Test of Mixed Progenitors" (TMP) was performed for the assessment whether the outcome of donor leukocyte infusion treatment could be predicted. Prior to DMNC infusions, the CFU-GM and BFU-E colony assays were performed for donor's and recipient's PBMC individually, as well as for the mixture of these cells at 1:1 ratio. The cells were plated either directly in the semisolid medium or after 24 h preincubation treatment. Significantly lower values for CFU-GM derived colonies were determined in TMP in comparison to the CFU-GM values obtained for the recipient's cells. The reduced number of CFU-GM was determined both in TMP performed without preincubation treatment, app. 80% and after the 24 h preincubation, app. 55%. The reduced number of BFU-E derived colonies (app. 44%) was observed only related to recipient's cells and after the preincubation treatment of the cells. The patient did not develop GVHD and currently (40 months after the first infusion). He remained well in complete hematological, cytogenetic, molecular and clinical remission, which was the most direct evidence of the GVL effect. The novel in vitro TMP test in which the specific contribution of donor's leukocytes to the growth of recipient's hematopoietic precursor cell growth was determined, correlated with the clinical outcome.
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PMID:Donor leukocyte infusion--the effect of mutual reactivity of donor's and recipient's peripheral blood mononuclear cells on hematopoietic progenitor cells growth. 1121 81

In this study we compared the lymphocyte reconstitution in 13 multiple myeloma (MM), nine acute myeloid leukemia (AML) and 10 chronic myeloid leukemia (CML) patients after allogeneic G-CSF-mobilized PBSC transplantation from HLA-identical siblings. Conditioning regimens included standard total body irradiation + cyclophosphamide (CY), or busulphan + CY, whereas VP-16 was added in patients with advanced disease. Overall comparable numbers of mononuclear cells, CD34+ cells and CD3+ T cells were infused in each group. A significantly higher CD3+ T cell number was observed in MM and AML than in CML patients 1 month after transplant. However, MM patients showed a faster and better recovery of CD4+ T cells than both AML and CML patients at 3 months (P = 0.01 and P = 0.01, respectively) and 12 months (P = 0.01 vs AML, while P = NS vs CML) after transplant, and had a CD4:CD8 ratio > 1 with a median CD4+ T cell value > 400/microl 1 year after transplant. Development of acute graft-versus-host disease (GVHD) did not affect CD4:CD8 ratios but patients who experienced acute GVHD > grade I had lower CD4+ and CD8+ T cell numbers at all time points. However, after excluding patients with GVHD > grade I, MM patients still showed a significantly higher CD4+ T cell value than patients with myeloproliferative diseases 1 year after transplant. These findings suggest that although allogeneic PBSC transplantation induces rapid immune reconstitution, different kinetics may occur among patients with hematological malignancies. In particular, the rapid reconstitution of CD4+ T cells in MM patients may contribute to the low transplant-related mortality achieved in this disease.
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PMID:Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells. 1122 73


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