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)

The treatment of steroid-refractory acute graft-versus-host disease (aGVHD) remains a clinical challenge, for which no standard therapy exists. Alemtuzumab is a humanized anti-CD52 monoclonal antibody (mAb) that has been successfully used as part of conditioning regimens for hematopoietic stem cell transplantation (HSCT) to prevent GVHD. The purpose of this study was to evaluate the safety and efficacy of alemtuzumab in treating steroid-refractory aGVHD (>or=grade II) following HSCT. Eighteen patients received subcutaneous alemtuzumab 10 mg daily on 5 consecutive days. Response was assessed at day 28 following initiation of alemtuzumab. Eight patients had grade II aGVHD, 8 had grade III, and 2 had grade IV. The main organ involved was the liver in 4 patients, gastrointestinal (GI) tract in 5, skin in 3, skin and liver in 3, and skin and GI tract in 3. Fifteen patients (83%) responded to alemtuzumab, including 6 (33%) with complete response. All 3 unresponsive patients died of GVHD. Ten of 15 responders are alive at median follow-up of 11 months (range: 3-24). Infections occurred in 14 patients, including cytomegalovirus (CMV) reactivation in 11. Grade 3 neutropenia and thrombocytopenia occurred in 6 and 4 patients, respectively. Alemtuzumab was well tolerated, and induces promising response rates in steroid-refractory aGVHD.
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PMID:Alemtuzumab for the treatment of steroid-refractory acute graft-versus-host disease. 1815 56

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for the BM dysfunction seen in patients with Shwachman-Diamond syndrome (SDS). Historically, these patients have fared poorly with intensive conditioning regimens with increased regimen-related toxicity especially involving the heart and lungs. We report our institutional experience with a reduced-intensity-conditioning protocol in seven patients with SDS and BM aplasia or myelodysplastic syndrome/AML. The preparative regimen consisted of Campath-1H, fludarabine and melphalan. Four patients received matched related marrow and three received unrelated stem cells (two PBSCs and one marrow). All but one was 8 of 8 allele HLA matched. All patients established 100% donor-derived hematopoiesis. No patient in this cohort developed grades III-IV GVHD. One patient had grade II skin GVHD that responded to systemic corticosteroids and one had grade I skin GVHD, treated with topical corticosteroids. Two out of seven patients developed bacterial infections in the early post transplant period. Viral infections were seen in four out of seven patients and were successfully treated with appropriate antiviral therapy. All patients are currently alive. These data indicate that HSCT with reduced-intensity conditioning is feasible in patients with SDS and associated with excellent donor cell engraftment and modest morbidity.
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PMID:Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome. 1850 Mar 73

Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment.
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PMID:Antifungal prophylaxis in adult stem cell transplantation and haematological malignancy. 1858 20

Bone marrow was the traditional graft source when we introduced these procedures to South Africa. Technical details were established using rabbits as the experimental model with translation into a formally structured clinical programme at the University of Cape Town, based in the Groote Schuur Hospital, in 1972. Lack of any infrastructure was overcome by the acquisition of the first continuous-flow cell separator in sub-Sahara to provide for granulocyte transfusions. This was shortly followed by creating a dedicated platelet donor panel and establishing a specialized laboratory for clonogenic assays, flow cytometry, and programmed freezing and by including cryopreservation. Development was constant and seamless but four distinct periods are recognizable. First, guided and constantly encouraged by Professor E Donnall Thomas, was the use of an unfractionated mononuclear population derived from multiple sternal and iliac crest aspirations where complications, as in other centres, included rejection and, particularly troublesome, acute as well as chronic GVHD. The second was centred on CsA in association with Professor Jean Borel at Sandoz in Basle, leading to a decrease in the incidence and severity of the latter immunologic phenomena but not to their abrogation. Third was the opportunity of working with Professor Herman Waldmann and Dr Geoff Hale, first in Cambridge and latterly in Oxford, on immunosuppression achieved by ex vivo T-cell depletion within the broad ambit of the Campath users group. It was here that there was pioneered the alternative new approach of adding the anti-CD 52 MoAb only to the graft in what has become known as the in-the-bag technique. The fourth, securely based on early laboratory and clinical experiences, was a switch to the use of PBSCs mobilized into the circulation with stimulatory peptides. In 1995, this original transplant team relocated to a new academic centre in the private sector and has continued to actively refine the programme over the subsequent decade: the facility at Groote Schuur hospital continues independently. Early recognition that accountability for these expensive and high profile procedures was an important obligation led to consecutive transplants being reported to the International and Autologous registries and now continuing to the Centre for Bone Marrow Transplant Research concurrently with the European Bone Marrow Transplant Registry. This disciplined approach has ensured that all data undergo constant audit and, on such a basis, underpin the unbroken accreditation extending over more than three and a half decades. With difficulties in finding sibling donors, a further achievement was the creation of The South African Bone Marrow Registry and now a proposal to also start a national transplant registry that will complement the survey currently being conducted, on a worldwide basis, by the European Group for Blood and Marrow Transplantation. It is concluded that a properly constituted and functioning multidisciplinary team can cost-effectively carry out immunohematopoietic stem cell grafting even in an under-resourced country with an outcome approximating that reported from recognized First World reference centres. The caveat is that, outside such comprehensive units, results may be less impressive, thereby arguing for resource allocation being directed to academically designated, rather than incentive-driven, preferred providers.
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PMID:Immunohematopoietic stem cell transplantation: introduction and 35 years of development in South Africa--the historical and scientific perspective. 1872 85

HLA-matched sibling donor (MSD) stem cell transplantation can cure>60% of pediatric patients with acute lymphoblastic leukemia (ALL), but <30% of patients will have a sibling donor. Alternative donor (AD) transplantation can be curative but has a higher risk of graft-versus-host disease (GVHD). The addition of alemtuzumab (Campath 1-H) to AD transplants produces in vivo T cell depletion, which may reduce the risk for GVHD. We now report the outcome for 83 children with ALL (41 MSD, 42 AD) undergoing stem cell transplantation in first or second complete remission. All patients received myeloablative conditioning, including cyclophosphamide, cytarabine arabinoside, and total-body irradiation, with alemtuzumab administered to AD recipients. GVHD prophylaxis consisted of a calcineurin inhibitor with either short-course methotrexate or prednisone. Disease-free survival (DFS) for MSD recipients was 72.3% (95% confidence interval [CI], 55.4%-83.6%) versus 62.4% (95% CI, 45.2%-75.4%) for AD recipients. The 100-day mortality was 7.1% in the AD group and 2.4% in the MSD group. Relapse rates were identical (24%). Treatment-related mortality, principally viral infection, explained the difference in survival. For children undergoing stem cell transplantation (SCT) from alternative donors, alemtuzumab with a myeloablative conditioning regimen resulted in DFS comparable to MSD.
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PMID:Comparable outcome of alternative donor and matched sibling donor hematopoietic stem cell transplant for children with acute lymphoblastic leukemia in first or second remission using alemtuzumab in a myeloablative conditioning regimen. 1894 Jun 79

Graft failure is a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). We used a nonmyeloablative conditioning regimen consisting of the lympho-depleting humanized CD52-antibody Campath-1H and fludarabine to rescue 12 consecutive children age 9 months to 17 years with engraftment failure after initial myeloablative HSCT. Primary diagnoses included lymphohematologic malignancies (n=6), severe combined immunodeficiency syndrome (SCID) (n=4), and metabolic diseases (n=2). The same stem cell donor was used as for the primary graft: mismatched family member (n=7), matched unrelated donor (n=4), or matched related donor (n=1). The patients received doses of CD34+ cells that did not significantly differ from those used in the initial, failed transplant. At a median follow-up of 51 months (range, 4 to 84 months), 6 of 6 patients with nonmalignant diseases and 4 of 6 patients with malignancy were alive. Two patients died, 1 patient from pulmonary toxicity and 1 from relapse, at 51 days and 8 months posttransplantation, respectively. All 12 patients initially achieved sustained neutrophil engraftment and complete donor chimerism by day 28. Six patients received donor lymphocyte infusion (DLI) after "rescue" therapy to maintain donor chimerism. At 6 months, 4 patients had complete donor cell engraftment, 4 had 15% to 89% stable donor chimerism, and 3 had developed secondary graft failure. This conditioning regimen was generally well tolerated; 4 of the 12 patients never became neutropenic, and 9 never became thrombocytopenic. Only 1 patient developed graft-versus-host disease (GVHD; grade 1), and none had chronic GVHD. Thus, the regimen that we describe can be used with minimal toxicity to effectively overcome graft failure after myeloablative HSCT in children.
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PMID:Successful treatment of stem cell graft failure in pediatric patients using a submyeloablative regimen of campath-1H and fludarabine. 1894 Jun 85

The humanized anti-CD52 monoclonal antibody alemtuzumab belongs to the family of Campath-1 antibodies, which were initially developed for their ability to prevent graft-versus-host disease (GVHD) and graft rejection in stem cell transplantation. Alemtuzumab is indicated for the treatment of chronic lymphocytic leukaemia (CLL) and has demonstrated considerable activity in relapsed/refractory disease and in previously untreated disease. It has been shown to induce minimal residual disease-negative responses as a single agent or as part of consolidation therapy in a meaningful proportion of patients with CLL and has shown promising activity in patients with high-risk cytogenetic markers. Alemtuzumab may also have significant activity in T-cell malignancies, such as mycosis fungoides and T-cell prolymphocytic leukaemia. Recent studies also have evaluated alemtuzumab as part of a conditioning regimen to prevent GVHD in stem cell transplantation. This article reviews our current understanding of alemtuzumab and discusses its emerging role in the treatment of CLL and other haematological malignancies.
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PMID:Rediscovering alemtuzumab: current and emerging therapeutic roles. 1918 94

Reduced-intensity conditioning (RIC) has allowed the use of allogeneic stem cell transplantation (alloSCT) for haematological malignancies in elderly patients. A major problem of this type of transplantation is the high incidence of persisting chronic graft-versus-host disease (GvHD), leading to increased morbidity and mortality. The inclusion of alemtuzumab added to the graft ('Campath in the bag') for donor T-cell depletion offers an easy procedure to diminish the incidence of GvHD. Good engraftment is observed in most patients, whereas almost no GvHD is observed after transplantation. Most patients become mixed chimeric after transplantation, requiring donor lymphocyte infusion for conversion to full donor chimerism. Although subsequent acute and chronic GvHD is observed in 50-60% of patients, it is responsive to therapy in many patients, resulting in a low incidence of persisting chronic GvHD. AlloSCT with RIC and alemtuzumab-induced T-cell depletion offers a suitable platform for the investigation of novel cellular immunotherapy.
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PMID:Reduced-intensity conditioning allogeneic stem cell transplantation with donor T-cell depletion using alemtuzumab added to the graft ('Campath in the bag'). 1956 8

Aplastic anemia (AA) is most frequently due to autoimmune attack on its own stem cells. Alemtuzumab is a monoclonal antibody which recognizes the CD52 antigen on the surface of T and B cells. It has proved useful in autoimmune diseases, lymphoproliferative conditions, and graft versus host disease. Based on its immunosuppressive properties, we treated 14 AA patients with alemtuzumab. Median age was 23 years. Ten milligrams of alemtuzumab were injected subcutaneously each day for five consecutive days. Cyclosporine A was also administered orally at a dose of 2 mg/kg every 12 h for 3 months, and then gradually tapered. Response to alemtuzumab was followed for a median of 20 months. There were eight responses (57.1%), two complete and six partial. Whereas six (42.8%) patients were non-responders. Median complete blood count values on alemtuzumab responders were Hb 13.1 mg/dL, absolute neutrophil count 2.4 x 10(9)/L, and platelets 97.5 x 10(9)/L. A good response was produced in 57% of AA patients with the administration of alemtuzumab, who lacked a stem cell donor.
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PMID:Subcutaneous alemtuzumab plus cyclosporine for the treatment of aplastic anemia. 1970 16

Reduced-intensity allogeneic stem cell transplantation (RIC-AlloSCT) is being increasingly considered for patients with aggressive lymphoma, but limited evidence exists in mantle cell lymphoma (MCL). We report a retrospective study of transplant outcomes of RIC-AlloSCT for MCL in 70 patients (median age, 48 years, range: 30-67 years), with 57 patients receiving an Alemtuzumab-containing regimen. Thirty-four percent of patients had received a prior autologous stem cell transplant. The 1- and 5-year nonrelapse mortality (NRM) was 18% (95% confidence interval [CI] 10-27) and 21% (95% CI 12-31), respectively. The incidence of severe (grade III and IV) acute graft-versus-host disease (aGVHD) was 10%, and the 5-year incidence of chronic GVHD (cGVHD) was 61%. The cumulative relapse risk was 65% (95% CI 48-77) at 5 years, significantly affected by disease status at transplant (P = .0495), specifically the presence of chemosensitive disease (P = .0364). Fifteen of 18 relapsed patients received donor lymphocyte infustion (DLI) (n = 14) or a second RIC-AlloSCT (n = 1), with 11 of 15 currently in CR. The 5-year overall survival (OS) and progression-free survival (PFS) were 37% (95% CI 25%-56%) and 14% (95% CI 6%-34%), respectively. Age at transplantation and having <2 prior lines of therapy influenced the OS, whereas having <2 prior lines of therapy was the only factor to influence PFS. The use of Alemtuzumab in the conditioning was associated with an improved OS at 3 years (P = .0271). RIC-AlloSCT is a potential treatment modality for aggressive MCL. For patients relapsing post-AlloSCT, the disease is salvageable with DLI. The timing of RIC-AlloSCT should be explored in prospective studies to establish the optimal role in the management of this aggressive lymphoma.
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PMID:Outcome following Reduced-Intensity Allogeneic Stem Cell Transplantation (RIC AlloSCT) for relapsed and refractory mantle cell lymphoma (MCL): a study of the British Society for Blood and Marrow Transplantation. 2039 79


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