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)

Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A chain (ST1 immunotoxin [ST1-IT]). These patients received intensive chemoradiotherapy consisting of cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Both anti-Leu1 + C and ST1-IT ex vivo treatments effectively depleted bone marrow of T cells (97% and 95%, respectively). Overall, primary and late graft failure each occurred in 4% of evaluable patients. The diagnosis of myelodysplasia was a significant risk factor for graft failure (P less than .001), and if myelodysplastic patients were excluded, there were no graft failures in major histocompatibility complex (MHC)-matched patients and 2 of 23 (8.7%) in MHC-mismatched patients. The actuarial risk of grade 2 to 4 acute graft-versus-host disease (GVHD) was 23% in MHC-matched patients and 50% in MHC-mismatched patients. In MHC-matched patients, acute GVHD tended to be mild and treatable with corticosteroids. Chronic GVHD was observed in 6 of 36 (17%) MHC-matched patients and none of 11 MHC-mismatched patients. There were no deaths attributable to GVHD in the MHC-matched group. Epstein-Barr virus-associated lymphoproliferative disorders were observed in 3 of 23 MHC-mismatched patients. The actuarial event-free survival was 38% in the MHC-matched patients versus 21% in the MHC-mismatched patients. However, if outcome is analyzed by risk of relapse, low-risk patients had a 62% actuarial survival compared with 11% in high-risk patients. These data indicate that the use of anti-CD5 MoAbs can effectively control GVHD in histocompatible patients, and that additional strategies are required in MHC-mismatched and high-risk patients.
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PMID:Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies. 171 80

Opportunistic infections have been a problem after BMT in CLL. We have allografted seven patients with B-CLL (n = 6) or B-prolymphocytic leukemia (n = 1) from matched siblings (n = 6) or a mismatched unrelated donor (n = 1). Amongst the first six, we saw two cases of recurrent or prolonged cytomegaloviremia and CMV disease, one listeria meningitis, and one fatal toxoplasma encephalitis. The latter two developed in the setting of steroid therapy of GVHD with extensive prior fludarabine therapy. Prophylaxis for opportunistic infections was developed on an ongoing basis as new infectious complications were seen. The current drug prophylaxis, which has been successful for eight months in the last patient despite pretreatment with fludarabine and steroid therapy for GVHD, is directed against pneumocystis, toxoplasma, fungi, and pneumococci. It includes immunoglobulin (for 3 1/2 months), pyrimethamine-sulfadiazine (for 4 months and during steroids), fluconazole (for 2 1/2 months), cotrimoxazole or pentamidine (for 2 years) and penicillin (lifelong). Dietary precautions are followed for 4 months and during steroids to prevent listeriosis. Four patients are alive in remission with no active infectious problems 8-44 months (median 29) after BMT. We recommend adoption of these or similar prophylactic measures for BMT in CLL as a baseline which can be modified if new infections are identified and according to individual needs.
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PMID:Antimicrobial prophylaxis to prevent opportunistic infections in patients with chronic lymphocytic leukemia after allogeneic blood or marrow transplantation. 925 Jul 91

Cord blood is increasingly used for hematopoietic stem cell transplantation since less severe graft-versus-host disease has been reported leading to the notion that cord blood is "naive." Human leucocyte antigen (HLA) class II molecules are expressed throughout B lymphocyte ontogeny (except the plasmocytes), are responsible for antigen presentation, and can also transmit signals. Cord blood B stimulate an allogeneic response, and this property is believed to indicate the presence of a class II-associated peptide. In this study we examined the capacity of cord blood B to transmit signals via HLA-DR. Activation and relocalization of protein kinase C (PKC) isoenzymes alpha and betaII was detected along with tyrosine kinase activation and proliferation. However, in contrast to resting adult B, generation of an intracellular calcium ([Ca++]i) flux and rapid aggregation were not detected. To address the question of whether or not HLA-DR signals throughout B lymphocyte ontogeny, we extended this study to include malignant adult B (B chronic lymphocytic leukemia [B-CLL], B mantle cell lymphoma, and B large cell leukemia). Tyrosine kinase activation and proliferation were observed in all these cell populations, albeit in the absence of [Ca++]i flux or an increase in PKC. HLA-DR therefore transmits signals throughout B lymphocyte ontogeny, although different signaling pathways are initiated in adult vs. fetal vs. malignant B. The lack of intracellular [Ca++]i flux in both cord blood and malignant B lymphocytes may represent a feature of HLA class II signaling at a particular stage of differentiation, although the downregulation of PKC clearly distinguishes between cord blood B and B-CLL.
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PMID:Signal transduction via human leucocyte antigen class II molecules distinguishes between cord blood, normal, and malignant adult B lymphocytes. 969 9

Following allogeneic stem cell transplantation (SCT), we studied the presence of donor and recipient derived cells within the CD19+ B cell fraction, in patients with B cell chronic lymphocytic leukemia (CLL). The chimeric status of the six patients studied was further investigated with minimal residual disease (MRD) detection, by sequencing and using patient-specific primers derived from junctional regions of clonally rearranged immunoglobulin heavy-chain (IgH) receptor genes. To date, five of six patients are alive with a median follow-up time of 24 months (range 15-60) post-SCT. All patients experienced acute and chronic graft-versus-host disease and responded clinically to SCT. All patients were MRD positive after SCT, which correlated to mixed chimerism within the CD19+ cell fraction in all samples except one (25/26). High levels of tumor necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 receptor (sIL-2R) indicated advanced disease, and patients with increased levels pre- and post-SCT were also those with the most long-lasting PCR-detectable MRD post-SCT. Hence, a high tumor burden pre-SCT may reflect the long duration of detectable MRD in patients with B-CLL after SCT. A durable anti-leukemic effect was probably important in these patients.
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PMID:Minimal residual disease is common after allogeneic stem cell transplantation in patients with B cell chronic lymphocytic leukemia and may be controlled by graft-versus-host disease. 1067 41

The anti-CD52 (Campath-1) monoclonal antibodies (Mabs) have a substantial history of use for controlling graft-versus-host disease in allogeneic bone marrow transplantation. Now, with the availability of a humanised form, alemtuzumab (Campath-1H), and the demonstration that this agent can reduce the tumour burden in B-CLL, a new niche may be found - as a potentially curative agent in which its tumour purging ability in vivo combines with its role as a conditioning agent in nonmyeloablative transplantation. Review of the literature shows that alemtuzumab has unique advantages as a method of depleting malignant lymphocytes, including those in patients resistant to conventional chemotherapy. Alemtuzumab can also be used in BMT for depletion of normal T and B lymphocytes of both the recipient and donor for prevention of graft rejection and GVHD. It allows good stem cell recovery with resultant rapid engraftment, has a low risk of EBV-triggered secondary malignancy and does not interfere with blood stem cell mobilisation. As a method of eliminating the malignant clone in B-CLL, alemtuzumab has shown remarkable efficacy in heavily pre-treated patients, a number of whom have progressed to autologous or allogeneic transplantation. Efficacy data are shown within the context of other transplantation data for B-CLL. These results indicate that the combination of tumour-depleting and immunosuppressive properties of alemtuzumab should be explored, with the hope of providing improved treatment options for elderly patients with advanced B-CLL or indolent lymphoma whose prognosis is too poor currently to allow treatment with traditional regimens of high-dose myeloablative chemotherapy.
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PMID:Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning? 1247 71

We studied the outcome of allo-SCT after reduced-intensity conditioning in relapsed or refractory indolent and aggressive lymphoid malignancies. All 54 patients (diagnosis: B-CLL n=13, indolent lymphoma n=12, aggressive lymphoma n=13, transformed lymphoma n=16) received conditioning with fludarabine and CY between July 2001 and November 2010. They underwent allo-SCT because of relapse after auto-SCT or because no other therapy could lead to a meaningful remission. Patients received an unmanipulated peripheral blood stem-cell graft. Median follow-up was 67 months. Thirty-two patients had received rituximab. Immediately after transplantation, remission status had improved in 21 patients, all without DLI. During the follow-up six additional patients achieved CR without further therapy. Four-year OS (EFS) was 46% (46%) for B-CLL, 83% (75%) for indolent lymphoma, 69% (55%) for aggressive lymphoma and 74% (67%) for transformed lymphoma (P=0.28 (P=0.54)). Forty two percent developed acute GVHD, 68% chronic GVHD (16% limited, 52% extensive). Previous auto-SCT did not influence OS, while acute GVHD did. Two-year non-relapse mortality was 16%. In conclusion, reduced-intensity conditioning with fludarabine-CY is feasible and effective for both indolent and aggressive lymphoid malignancies, even after previous auto-SCT. Because of the excellent anti-B-cell/lymphoma activity fludarabine-CY decreases tumor load, gaining time for the development of a graft versus lymphoma effect.
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PMID:Allogeneic transplantation after reduced-intensity conditioning with fludarabine-CY for both indolent and aggressive lymphoid malignancies. 2441 17