Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alemtuzumab (Campath 1H -MabCampath), initially used for prophylaxis of graft versus host disease in allogenic transplantaion, is now increasingly used for refractory chronic lymphatic leukaemia (CLL). Its efficacy has been well documented in this--the commonest form of leukaemia. Alemtuzumab is associated with severe immunosuppression, allergic reactions and thrombocytopenia. Data sheet and information supplied by the manufacturer confirm the rare occurrence of serious immune thrombocytopenia, recommending discontinuation of therapy when platelet counts fall below 50x10(9)/l. We report a patient with refractory CLL in which relentless progressive cytopenia occurred despite the discontinuation of alemtuzumab therapy while the platelet count was over 97x10(9)/l. Marrow biopsy showed increased megakaryocytes, the patient bleed uncontrollably and died of cerebral haemorrhage with a platelet count <10x10(9)/l. Data on the predictive factors underlying this complication are few and deserve further study as this drug is increasingly used the treatment of CLL.
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PMID:Fatal thrombocytopaenia temporally related to the administration of alemtuzumab (MabCampath) for refractory CLL despite early discontinuation of therapy. 1576 82

One of the important approaches for further prolonging remission duration and eradicating minimal residual disease in acute leukemia is immunotherapy. Four kinds of immunotherapy for acute leukemia are under investigation: (1) monoclonal antibodies, among them, Mylotarg (cytotoxic antibiotic calicheamicin linked to CD33 Mab) is given for the treatment of refractory or relapsed acute myeloid leukemia and molecular relapse in acute promyelocytic leukemia with good results, Campath-1H (antiCD52 Mab) is administered in the treatment of prolymphocytic leukemia and Rituximab (anti-CD20 Mab) in B-PLL with high complete remission rates. Other Mabs under preclinical and clinical trials include anti-IL-2 receptor Mab for the treatment of acute T lymphocytic leukemia, anti-220 kD Mab-6G7 for acute leukemias, recombinant immune toxin BL22 (anti-CD22) for hairy cell leukemia and Mabs labeled with radio-isotopes for different types of acute leukemias; (2) adoptive cellular immunotherapy using cytokine-induced killer cell, alloreactive NK cells, allogeneic or autologous leukemic-specific CD8(+) cytotoxic T lymphocytes, and other immune effector cells; (3) cytokines and other immune modulators comprising IL-2, IL-12, GM-CSF, CD40L, FLT-3L and thalidomide and its derivatives; (4) leukemia vaccines of several different formulations including antigen-specific, leukemia cell-based, leukemia antigen-pulsed dendritic cell (DC) and leukemia-derived DC vaccines, the latter two formulations are more attractive. In conclusion, up to now, the most effective example of immunotherapy in acute leukemia is provided by the administration of Mabs, and the majority of other approaches in immunotherapy for acute leukemia although promising, need further studies.
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PMID:[Present status in studying immunotherapy for acute leukemia and its perspective--Editorial]. 1585 71

Alemtuzumab (anti-CD52; Campath-1H) is effective in fludarabine-refractory chronic lymphocytic leukemia (CLL), but is associated with infection and early onset neutropenia. To reduce toxicity, filgrastim (G-CSF) was administered concurrently with alemtuzumab. In total, 14 CLL patients (median age 59) with a median of 3.5 prior regimens (range 1--12) received i.v. alemtuzumab, stepped up from 3 to 30 mg the first week, then 30 mg thrice weekly for 12 weeks. Filgrastim 5 microg/kg was administered daily 5 days before and throughout alemtuzumab therapy. Six patients developed cytomegalovirus (CMV) reactivation 3--6 weeks into treatment; six patients developed fever, three neutropenia, and one pneumonia. The patient with CMV pneumonia died; ganciclovir cleared CMV in the other patients. Five patients developed early neutropenia (weeks 2--5). Four patients developed delayed neutropenia (weeks 10--13) unassociated with CMV reactivation. Nine patients ceased therapy because of infectious and hematologic toxicity. Five partial responses were noted, all in patients with lymph nodes>cm, lasting a median of 6.5 months (range 5--13). Filgrastim and alemtuzumab were given concurrently with manageable infusion toxicity and clinical activity, but the efficacy of this regimen was limited by delayed neutropenia of unclear etiology and CMV reactivation. Filgrastrim should not be administered prophylactically during alemtuzumab therapy outside clinical trials.
Leukemia 2005 Jul
PMID:Filgrastim and alemtuzumab (Campath-1H) for refractory chronic lymphocytic leukemia. 1585 11

Treatment of adult T-cell leukemia (ATL) remains difficult. Alemtuzumab with or without nucleoside analogs such as pentostatin may provide a role in this setting. However, the associated immunosuppression is a concern in patients with viral-mediated disease.
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PMID:Complete response in a patient with adult T-cell leukemia (ATL) treated with combination of alemtuzumab and pentostatin. 1597 4

Two patients with pure red cell aplasia (PRCA) refractory to anti-thymocyte globulin, prednisolone, cyclophosphamide, fludarabine, mitoxantrone, dexamethasone and cyclosporine, were treated with alemtuzumab (anti-CD52 antibody). Case 1, a 35-year-old man with idiopathic PRCA, remitted completely with 130 mg of alemtuzumab. Case 2, a 42-year-old man with PRCA due to T-cell large granular lymphocyte (T-LGL) leukaemia, achieved complete remission of the PRCA with 490 mg of alemtuzumab, although the T-LGL leukaemia responded only transiently. There were no significant side effects, and normalization of erythropoiesis was durable. Alemtuzumab is active in PRCA that is idiopathic or secondary to T-cell lymphoproliferative diseases.
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PMID:Alemtuzumab induced complete remission of therapy-resistant pure red cell aplasia. 1611 36

T- cell Prolymhocytic leukemia (T-PLL) is a rare mature post-thymic T-cell malignancy that is usually reported in the elderly and follows an aggressive course. A 68 year old male presented with a history of weakness and weight loss of two months duration. Clinical examination revealed pallor, enlarged cervical and axillary lymph nodes and splenomegaly. He also had a maculo- papular skin rash. There was marked leucocytosis, anemia and thrombocytopenia (WBC 445 x 103 sub/ml, Hb 8.5 gm/dl, Platelet 25 x 103 sub/microl) with 60% prolymphocytes in the peripheral blood. Bone marrow was hypercellular with an excess of prolymphocytes. Flow cytometric analysis of the bone marrow showed positivity for CD2, CD3, CD4, CD5 and CD 7. T- PLL is a rare T cell disorder with characteristic clinical and laboratory features. Currently, no optimal treatment exists although there has been some success with 2'- deoxycoformycin or Campath-1H.
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PMID:T- cell prolymphocytic leukemia - a rare case. 1614 12

Alemtuzumab is an exciting targeted therapy for patients with CD52-sensitive malignancies. The drug is being used in a variety of hematologic malignancies in different dosing schedules and different routes of administration. The Cancer and Leukemia Group B is conducting a study using alemtuzumab as consolidation treatment for patients with B-CLL. The group also is conducting a phase I and II dose-escalation study using alemtuzumab during intensification therapy in adults with untreated acute lymphoblastic leukemia. A national pharmaceutical protocol is actively accruing participants for a trial in which alemtuzumab is used in combination with fludarabine for relapsed and refractory B-CLL. The SQ route of administration is gaining popularity because it is highly effective with fewer side effects than IV infusions. Nurses administering alemtuzumab are in a unique position to ensure patient safety and tolerance of the therapy. By understanding the mechanism of action and the potential complications associated with alemtuzumab, nurses will be better able to provide optimal care to patients as the use of targeted monoclonal therapy continues to progress.
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PMID:Alemtuzumab (Campath 1-H). 1623 92

New insights into prognostic markers and the pathophysiology of chronic lymphocytic leukemia (CLL) are beginning to change the concept of CLL treatment. Alemtuzumab has evolved as a potent and effective therapeutic option for patients with CLL. Specifically, alemtuzumab has demonstrated substantial efficacy in fludarabine-refractory patients and has shown impressive responses when administered subcutaneously in first-line therapy. A group of experts gathered to discuss new data related to the use of alemtuzumab in CLL and to assess its place in the rapidly changing approach to treating patients with this disease. The main goals of this program were to update the management guidelines that were previously developed for alemtuzumab-treated patients and to provide community oncologists with guidance on the most effective way to integrate alemtuzumab into a CLL treatment plan.
Leukemia 2005 Dec
PMID:The evolving role of alemtuzumab in management of patients with CLL. 1623 12

Alemtuzumab is a humanized IgG1 kappa antibody directed against CD52, a glycosyl-phosphatidylinositol linked cell-membrane protein of unknown function. Herein, we demonstrate that alemtuzumab promotes rapid death of chronic lymphocytic leukemia (CLL) cells in vitro, in a complement and accessory cell free system. Using minimal detergent solubilization of CLL membranes, we found that CD52 colocalizes with ganglioside GM-1, a marker of membrane rafts. Fluorescence microscopy revealed that upon crosslinking CD52 with alemtuzumab+anti-Fc IgG, large patches, and in many cases caps, enriched in CD52 and GM-1 formed upon the CLL cell plasma membrane. Depletion of membrane cholesterol or inhibition of actin polymerization significantly diminished the formation of alemtuzumab-induced caps and reduced alemtuzumab-mediated CLL cell death. We compared alemtuzumab-induced direct cytotoxicity, effector cell-mediated toxicity and complement-mediated cytotoxicity of CLL cells to normal T cells. The direct cytotoxicity and observed capping was significantly greater for CLL cells as compared to normal T cells. Cell-mediated and complement-mediated cytotoxicity did not significantly differ between the two cell types. In summary, our data support the hypothesis that alemtuzumab can initiate CLL cell death by crosslinking CD52-enriched lipid rafts. Furthermore, the differential direct cytotoxic effect suggests that CD52 directed antibodies could possibly be engineered to more specifically target CLL cells.
Leukemia 2006 Feb
PMID:Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism. 1634 Oct 49

Nonmyeloablative stem cell transplants provide a viable therapeutic option for older patients or patients with comorbid conditions, who were previously deemed to be ineligible for transplantation. Despite improvements in clinical outcomes, graft-versus-host disease (GVHD) remains a significant and potentially lethal complication. One approach by which GVHD has been managed is through introduction of new agents, such as alemtuzumab, into the conditioning regimen. Alemtuzumab is a humanized monoclonal antibody that targets the CD52 antigen, which is highly expressed on both B and T lymphocytes. By depleting T cells in both the donor and the recipient, alemtuzumab has been shown to prevent development of both acute and chronic GVHD, without inhibiting the benefits associated with the graft-versus-leukemia effect. Clinical trials have shown that alemtuzumab is able to decrease the incidence of acute and chronic GVHD without impairing engraftment. Furthermore, in chronic lymphocytic leukemia therapy, alemtuzumab has been shown to purge malignant cells from the host to allow for harvesting for the purpose of autologous transplantation. Despite results showing that alemtuzumab can play an important role in managing GVHD, little information is available regarding a standardized dosing schedule. Greater insight into alemtuzumab's pharmacokinetic activity would assist in developing a schedule that can optimize alemtuzumab-mediated T-cell depletion to prevent GVHD, while retaining sufficient host T-cell activity to encourage the graft-versus-leukemia effect and prevent relapse.
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PMID:The role of alemtuzumab in nonmyeloablative hematopoietic transplantation. 1672 Feb 2


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