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

For lymphoproliferative disease, RIST is a curative treatment option. Here, we review the patients with follicular lymphoma(FL), diffuse large B cell lymphoma(DLBCL) and mantle cell lymphoma(MCL), who were mainly transplanted at Toranomon Hospital and National Cancer Center Hospital. In our series, 1-year disease-free survival rate were 100%, 56% and 63%, respectively. Main cause of death was treatment related mortality associated with graft-versus-host disease(GVHD) rather than disease progression in both DLBCL and MCL. These data suggest that intensified GVHD prophylaxis would improve the survival rates. We are now undergoing multi-center phase I/II study for RIST using fludarabine and busulfan. In designing our future study, we held nationwide survey to retrospectively evaluate the efficacy of RIST for various types of malignant lymphoma diseases. We also review the literature about RIST for acute lymphoblastic leukemia.
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PMID:[Reduced-intensity stem cell transplantation (RIST) for lymphoproliferative diseases]. 1451 27

We carried out HLA-matched related (n = 16) and unrelated (n = 17) hematopoietic cell transplantation (HCT) in 33 patients with relapsed and refractory mantle cell lymphoma after nonmyeloablative conditioning with fludarabine and 2 Gy total body irradiation. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Fourteen patients had failed high-dose autologous HCT. Of the 33 patients studied, 31 had stable engraftment, whereas 2 patients experienced nonfatal graft rejections. The incidences of acute grades II, III, and IV, and chronic graft-versus-host disease (GVHD) were 27%, 17%, 13%, and 64%, respectively. The overall response rate in the 20 patients with measurable disease at the time of HCT was 85% (n = 17; 75% complete remissions [CR] and 10% partial remissions [PR]), whereas 3 patients had progressive disease. Only one of the 17 patients who responded and none of the 13 who received transplants in CR had disease relapse with a median follow-up of 24.6 months. Relapse and nonrelapse mortalities were 9% and 24%, respectively, at 2 years. The Kaplan-Meier probabilities of overall and disease-free survivals at 2 years were 65% and 60%, respectively. Allogeneic HCT after nonmyeloablative conditioning is a promising salvage strategy for patients with relapsed and refractory mantle cell lymphoma. The high response and low relapse rates with this approach suggest that mantle cell lymphoma is susceptible to graft-versus-tumor responses.
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PMID:Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma. 1530 87

We report the outcomes after reduced-intensity conditioning allogeneic stem cell transplantation (RIT) for non-Hodgkin lymphoma (NHL) in 88 patients (low-grade NHL [LG-NHL], n = 41; high-grade NHL [HG-NHL], n = 37; mantle cell lymphoma [MCL], n = 10). Thirty-seven patients had previously received autografts, and 21 were in complete remission (CR) at transplantation. Conditioning therapy consisted of alemtuzumab, fludarabine, and melphalan. Sixty-five patients received peripheral blood stem cells (PBSCs) from HLA-identical siblings, and 23 received bone marrow (BM) from matched unrelated donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporin A. Grade III-IV acute GVHD developed in 4 patients, and chronic GVHD developed in 6 patients. With a median follow-up of 36 months (range, 18-60 months), the actuarial overall survival (OS) rates at 3 years were 34% for HG-NHL, 60% for MCL, and 73% for LG-NHL (P < .001). The 100-day and 3-year transplant-related mortality (TRM) rates for patients with LG-NHL were 2% and 11%, respectively, and were better (P = .01) than they were for patients with HG-NHL (27% and 38%, respectively). The actuarial current progression-free survival (PFS) rate at 3 years, including the rate for patients who achieved remission after donor lymphocyte infusion (DLI) for progression, was 65% for LG-NHL, 50% for MCL, and 34% for HG-NHL (P = .002). Twenty-one patients underwent DLI for matched related donor (MD)-persistent disease or relapse, and 15 underwent DLI for mixed hematopoietic chimerism. Patients who experienced relapses of LG-NHL and chronic lymphocytic leukemia (CLL) achieved excellent PFS with extremely low TRM and GVHD, even when matched related donors were unavailable.
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PMID:Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma. 1530 95

Mantle cell lymphoma is a subtype of non-Hodgkin's lymphoma. Mantle cell is generally considered incurable with a median overall survival of about 3 years. It is most common in 50 - 70 year old individuals and for this reason transplantation is not a common therapeutic option. Autologous stem cell transplantation does not appear to improve survival with most patients relapsing after transplant and no disease-free plateau. We present 6 mantle cell patients that had a mean of 3 different types of therapy prior to allogeneic transplantation. Allogeneic transplantation is associated with substantial mortality post-transplant from acute toxicity and GVHD. Despite the extensive amount of pretransplant therapy in our patient population, there was no transplant related mortality. All patients are alive and in remission a median of 4.3 plus years after transplantation. Survival from the date of diagnosis is a median of 6.5 plus years. The results of this series would suggest that in a selected group of patients allogeneic stem cell transplantation may be the treatment of choice for lymphomas not curable by standard therapy or autotransplant.
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PMID:Allogeneic stem cell transplantation for mantle cell lymphoma--does it deserve a better look? 1562 4

We report the outcome following RIT for NHL in 88 patients (LG-NHL n = 41, HG-NHL n = 37, MCL n = 10). Thirty-seven had received prior autografts and 21 were in CR at transplant. Conditioning was with alemtuzumab, fludarabine and melphalan. Sixty-five patients received PBSC from HLA-identical siblings and 23 received BM from matched unrelated donors. GVHD prophylaxis was with cyclosporin A. Grade III-IV acute GVHD developed in 4 patients and chronic GVHD in 6 patients. With a median follow-up of 36 months (range 18-60), the actuarial overall survival (OS) at 3 years was 34% for HG-NHL, 60% for MCL and 73% for LG-NHL (p < or = 0.001). The 100-day and 3-year TRM for patients with LG-NHL were 2% and 11%, respectively, and were better (p = 0.01) than for patients with HG-NHL (27% and 38%, respectively). The actuarial current progression free survival (PFS) at 3 years, including those who achieved remission following DLI for progression, was 65% for LG-NHL 50% for MCL and 34% for HG-NHL (p = 0.002). Twenty-one patients received DLI for MRD, persistent disease or relapse and 15 received DLI for mixed hematopoietic chimerism. Patients with relapsed LG-NHL and CLL achieve excellent PFS with extremely low TRM and GVHD, even when matched family donors are unavailable.
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PMID:Outcome following alemtuzumab (CAMPATH-1H)-containing reduced intensity allogeneic transplant regimen for relapsed and refractory non-Hodgkin's lymphoma (NHL). 1573 76

A 51-year-old man developed progressive debilitating limb and respiratory muscle weakness while undergoing treatment for chronic graft-versus-host disease secondary to allogeneic bone marrow transplant for mantle cell lymphoma. He had a normal serum creatine kinase level and acetylcholine receptor antibodies were negative. Electromyography showed a severe, nonirritable myopathy and a sensory motor axonal polyneuropathy. A muscle biopsy showed a necrotizing, vacuolar myopathy with many fibers containing autophagic and red-rimmed vacuoles, suggestive of an amphiphilic drug myopathy. The patient's strength and function improved significantly after discontinuation of hydroxychloroquine.
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PMID:Hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft-versus-host disease. 1579 21

We treated 17 patients with refractory (n = 7) or relapsed lymphoid malignancy (n = 10) following allogeneic HSCT with donor lymphocyte infusions (DLI). Patients with low-grade disease received DLI alone (n = 7) or following radiotherapy (n = 1). Patients with aggressive disease (n = 9) received prior chemotherapy. Nine out of 15 patients receiving DLI from sibling donors responded after one (n = 6), two (n = 2) and three (n = 1) infusions. Both MUD recipients achieved CR after two and three DLI. In all, 10/17 patients achieved CR including 3/4 patients with chronic lymphatic leukaemia (CLL), 4/4 with mantle cell lymphoma (MCL), 3/4 with follicular NHL but 0/5 with aggressive NHL/Richters. The median CD3 cell dose to achieve CR for siblings was 2 x 10(7)/kg. One patient with CLL had a second transplant following DLI-induced aplasia and is in CR at 14 months giving a final CR rate of 64%. Grade II-IV acute GVHD developed in 45% and chronic GVHD in 8/9 evaluable patients. Of the 11 patients finally achieving CR, one patient with MCL relapsed at 18 months post-DLI but all others remain in remission with a median follow-up of 40 months (range 12-64 months). Low-grade NHL and MCL have a high response rate and sustained remissions following DLI. Aggressive disease responds poorly however, despite pre-DLI chemotherapy.
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PMID:Donor lymphocyte infusions can result in sustained remissions in patients with residual or relapsed lymphoid malignancy following allogeneic haemopoietic stem cell transplantation. 1598 Aug 79

Although the prognosis for mantle cell lymphoma (MCL) patients has improved in recent years, the outlook for those with advanced or recurrent disease remains poor. High-dose chemotherapy and autografting performed early in responding patients appears to be a method to extend progression-free survival (PFS) and overall survival (OS). The use of monoclonal antibody therapy added into the initial therapy and in the peritransplant period may improve on these results. Myeloablative allogeneic transplant appears to be a modality capable of providing curative therapy, but is plagued by a high treatment-related mortality, especially in older patients. Reduced-intensity conditioning allografting have fewer problems associated with the initial phase of transplant and hence may be preferred for those patients for whom an allograft is considered but have comorbid conditions or age issues that preclude a full allograft. Long-term results are lacking and the side effects associated with chronic GVHD may be as significant and debilitating. Trials designed to look at newly diagnosed patients with MCL examining the outcomes after planned autologous and allogeneic transplant as part of the initial management are needed to confirm the role of these various modalities in the overall therapy of this poor-outcome lymphoma.
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PMID:Stem cell transplantation for mantle cell lymphoma: if, when and how? 1600 6

Autologous hematopoietic stem cell transplantation is widely accepted as effective therapy for patients with relapsed aggressive B-cell non-Hodgkin's lymphoma, and to a lesser extent, for indolent and mantle cell lymphoma, resulting in prolonged disease-free survival. Despite these advances, disease recurrence remains a problem and a major clinical challenge. Allogeneic transplantation has also been increasingly utilized in patients with relapsed aggressive and indolent lymphoma but is associated with high toxicity and graft-versus-host disease. Recently, nonmyeloablative preparatory regimens have shown encouraging results, attributed to graft-versus-lymphoma effects. Rituximab, a monoclonal antibody targeted against the CD20 antigen, is a potent therapeutic tool with documented efficacy in B-cell lymphomas. It is effective when used alone or in combination with chemotherapy, resulting in a significantly improved response rate compared with chemotherapy alone, in both aggressive and indolent lymphomas. Increasing evidence suggests that rituximab is also effective at in vivo purging prior to transplantation and may prevent relapse by eradication of residual disease when administered after transplantation. This review summarizes the available data on the use of rituximab and discusses the current evidence for its role in conjunction with auto- and allotransplantation.
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PMID:The role of the anti-CD20 antibody rituximab in hematopoietic stem cell transplantation for non-Hodgkin's lymphoma. 1600 42

A 57-year-old man underwent an autologous hematopoietic stem cell transplant for mantle cell lymphoma in August 1999. Anemia and thrombocytopenia appeared in November 2001. He was diagnosed with further hematological examination as having acute myeloid leukemia with multilineage dysplasia following secondary myelodysplastic syndrome. He received the allogeneic hematopoietic stem cell transplant from his HLA DRB1 locus mismatched brother in May 2002. The nonmyeloablative preparative regimen consisted of fludarabine 30mg/m2 for 6 days and busulfan 4mg/kg for 2 days. Eosinophilia, decrease of lacrimal fluid and liver dysfunction appeared on Day 104. We diagnosed this as chronic GVHD and treated the patient with prednisolone 10 mg/day. Thereafter, his chronic GVHD gradually improved. He had fever and myalgia in the extremities and lumbar region with elevated serum CPK and aldolase in January 2003. Histological examination led to a diagnosis of polymyositis simultaneously with chronic GVHD. Prednisolone 50 mg/day as an initial dose was started for the polymyositis following which the prednisolone dose was gradually tapered off. The polymyositis improved promptly after the administration of prednisolone and remains in remission with a current maintenance program of prednisolone 5 mg/day.
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PMID:[Chronic GVHD with polymyositis after non-myeloablative stem cell transplantation]. 1644 Aug 6


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