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Alemtuzumab
Terms modified by Alemtuzumab Selected AbstractsA case of hepatosplenic ,,, T-cell lymphoma with a transient response to Fludarabine and AlemtuzumabEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006S. Mittal Abstract:, Hepatosplenic ,,, T-cell lymphoma is a rare, usually fatal lymphoma and available literature on management is sparse. Allografting is probably the only curative option. We describe a further case with a dramatic, though transient response to Fludarabine and Alemtuzumab combination, following a failure of conventional chemotherapy. Given the dreadful prognosis with conventional chemotherapy, it is a regimen worth pursuing as a disease reduction strategy prior to allograft where appropriate. [source] Antifungal prophylaxis in adult stem cell transplantation and haematological malignancyINTERNAL MEDICINE JOURNAL, Issue 6b 2008M. A. Slavin Abstract 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. [source] Investigation of Lymphocyte Depletion and Repopulation Using Alemtuzumab (Campath-1H) in Cynomolgus MonkeysAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010D. J. Van Der Windt As the target CD52 molecule is expressed on erythrocytes of most nonhuman primate strains, using alemtuzumab in these species would cause massive hemolysis. Six cynomolgus monkeys of Indonesian origin, screened by agglutination assay for absence of CD52 on erythrocytes, were administered alemtuzumab in a cumulative dose to a maximum of 60 mg/kg. In two monkeys, mycophenolate mofetil (MMF) was added as maintenance therapy. Complete depletion of T and B lymphocytes (>99.5%) was achieved with 20 mg/kg alemtuzumab and was more profound than in monkeys treated with antithymocyte globulin (n = 5), as quantified by flow cytometry. Repopulation was suppressed by weekly injections of 10 mg/kg. Without MMF, repopulation of CD20+B cells and CD8+T cells was complete within 2 and 3 months, respectively, and repopulation of CD4+T cells was 67% after 1 year. MMF significantly delayed CD4+T-cell repopulation. Among repopulating CD4+ and CD8+ T cells, a phenotypic shift was observed from CD45RAhiCD62Lhi naïve cells toward CD45RAloCD62Llo effector memory cells. In lymph nodes, the depletion of naïve cells was more profound than of memory cells, which may have initiated a proliferation of memory cells. This model offers opportunities to investigate lymphocyte depletion/repopulation phenomena, as well as the efficacy of alemtuzumab in preclinical transplantation models. [source] BAFF Is Increased in Renal Transplant Patients Following Treatment with AlemtuzumabAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009D. Bloom Alemtuzumab is a monoclonal antibody that depletes T and B cells and is used as induction therapy for renal transplant recipients. Without long-term calcineurin inhibitor (CNI) therapy, alemtuzumab-treated patients have a propensity to develop alloantibody and may undergo antibody-mediated rejection (AMR). In pursuit of a mechanistic explanation, we analyzed peripheral B cells and serum of these patients for BAFF (Blys) and BAFF-R, factors known to be integral for B-cell activation, survival, and homeostasis. Serum BAFF levels of 22/24 alemtuzumab-treated patients were above normal range, with average levels of 1967 pg/mL compared to 775 pg/mL in healthy controls (p = 0.006). BAFF remained elevated 2 years posttransplant in 78% of these patients. BAFF-R on CD19+ B cells was significantly downregulated, suggesting ligand/receptor engagement. BAFF mRNA expression was increased 2,7-fold in CD14+ cells of depleted patients, possibly linking monocytes to the BAFF dysregulation. Addition of recombinant BAFF to mixed lymphocyte cultures increased B-cell activation to alloantigen, as measured by CD25 and CD69 coexpression on CD19+ cells. Of note, addition of sirolimus (SRL) augmented BAFF-enhanced B-cell activation whereas CNIs blocked it. These data suggest associations between BAFF/BAFF-R and AMR in alemtuzumab-treated patients. [source] Early and Limited Use of Tacrolimus to Avoid Rejection in an Alemtuzumab and Sirolimus Regimen for Kidney Transplantation: Clinical Results and Immune MonitoringAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009S. J. Knechtle Alemtuzumab induction with 60 days of tacrolimus treatment and continuous sirolimus treatment prevented acute rejection in nine of 10 consecutive renal allograft recipients. All patients are alive with a functioning kidney graft at 27,39 months of follow-up. Extensive immune monitoring was performed in all patients. Alloantibody detection, cytokine kinetics assay (CKA), and trans vivo delayed-type hypersensitivity (DTH) assay were performed every 6 months showing correlation with clinical evolution. Despite alloantibody presence in five patients, eight patients remain without the need for specific treatment and only sirolimus monotherapy in decreasing dosage. Four patients take only 1 mg sirolimus daily with levels of 3,4 ng/mL. One patient showed clinical signs of rejection at month 9 post-transplant, with slow increase in serum creatinine and histological signs of mixed cellular (endarteritis) and humoral rejection (C4d positivity in peritubular capillaries and donor-specific antibody (DSA)). In summary, the addition of tacrolimus therapy for 2 months to a steroid-free, alemtuzumab induction and sirolimus maintenance protocol limited the previously shown acute rejection development. Nevertheless, alloantibody was present in serum and/or C4d present on 1-year biopsy in half the patients. The combination of CKA and DSA monitoring or the performance of transvivo DTH correlated with immune status of the patients. [source] Stability of Alemtuzumab for Low-Dose Induction and Test DosesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009L. C. Vermeulen No abstract is available for this article. [source] Two Hundred Living Donor Kidney Transplantations Under Alemtuzumab Induction and Tacrolimus Monotherapy: 3-Year Follow-UpAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009H. P. Tan Alemtuzumab has been used in off-label studies of solid organ transplantation. We extend our report of the first 200 consecutive living donor solitary kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning to 3 years of follow-up. We focused especially on the causes of recipient death and graft loss, and the characteristics of rejection. The actuarial 1-, 2- and 3-year patient and graft survivals were 99.0% and 98.0%, 96.4% and 90.8% and 93.3% and 86.3%, respectively. The cumulative incidence of acute cellular rejection (ACR) at the following months was 2%,6, 9.0%,12, 16.5%,18, 19.5%,24, 23.5%,30, 24.0%,36 and 25%,42. The mean serum creatinine (mg/dL) and glomerular filtration rate (mL/min/1.73 m2) at 1 and 3 years were 1.4 ± 0.6 and 58.7 ± 21.6 and 1.5 ± 0.7 and 54.9 ± 20.9, respectively. Fifty (25%) recipients had a total of 89 episodes of ACR. About 88.7% of ACR episodes were Banff 1, and of those, 82% were steroid-sensitive. Nine (4.5%) recipients had antibody-mediated rejection (AMR). About 76.5% were weaned but only 46% are currently on spaced dose (qod or less) tacrolimus monotherapy, and 94.4% remained steroid-free from the time of transplantation. Infectious complications were uncommon. This experience suggests the 3-year efficacy of this approach. [source] CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1HAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008D. D. Bloom Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3+ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4+CD25+FOXP3+ lymphocytes increased significantly within the CD4+ T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4+CD25+FOXP3+ cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo. [source] Homeostatic Repopulation by CD28,CD8+ T Cells in Alemtuzumab-Depleted Kidney Transplant Recipients Treated With Reduced ImmunosuppressionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008P. Trzonkowski Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation. We found that after alemtuzumab induction the recovery of CD8+ T cells was much faster than that of CD4+ T cells. It was complete 6 months posttransplant while CD4+ T cells did not fully recover even 15 months posttransplant. Repopulating CD8+ T cells were mainly of immunosenescent CD28,CD8+ phenotype. In a series of in vitro experiments we showed that CD28,CD8+ T cells might suppress proliferation of CD4+ T cells. There were three successfully treated acute rejections during the study (first at +70 day, two others +12 months) that occurred in patients with the lowest level of CD28,CD8+ T cells. We hypothesize that expanded CD28,CD8+ T cells might compete for ,immune space' with CD4+ T cells suppressing their proliferation and therefore delaying CD4+ T-cells recovery. This delay might be associated with the clinical outcome as CD4+ T cells, notably CD4+ T effector memory cells, were shown to be associated with rejection. [source] Analysis of Subcutaneous (SQ) Alemtuzumab Induction Therapy in Highly Sensitized Patients Desensitized With IVIG and RituximabAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2008A. A. Vo Here we report on our experience with subcutaneous (SQ) Alemtuzumab in an uncontrolled study in highly HLA-sensitized patients (HS). From 3/05,4/07, 54 HS patients received Alemtuzumab 30 mg SQ as induction. Patient and graft survival, AR episodes, serum creatinines, absolute lymphocyte counts, monthly PCR monitoring for viruses, AE/SAEs and infectious complications were monitored. No patient to date has developed acute injection-related reactions after SQ Alemtuzumab; however, bone marrow suppression was occasionally seen requiring reduction or elimination of mycophenolate mofetil approximately 1,2 months posttransplant. Patient and graft survival at 12 M was 98%/96%, respectively. AR episodes occurred in 35% with 20% being C4d+ AMR. Mean SCrs at 12 M were 1.4 ± 0.3 mg/dL. The nadir ALC was 0.17 ± 0.19 within 24 h and sustained up to 365 days posttransplant. Infections occurred in eight patients (five with polyoma BK viremia [PBK], one CMV/PBK and two CMV viremia). SQ Alemtuzumab was well tolerated and resulted in prolonged lymphocyte depletion. Compared to our previous experience with daclizumab and rabbit ATG induction in HS patients, single-dose SQ Alemtuzumab was more cost effective, showed similar infection rates and did not reduce the AMR rates posttransplant. Although uncontrolled, these observations suggest that induction therapy with Alemtuzumab appears feasible and indeed promising, but awaits more definitive study. [source] Recovery of Functional Memory T Cells in Lung Transplant Recipients Following Induction Therapy with AlemtuzumabAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2007A. Zeevi Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow® and T Cell MemoryÔ, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4,5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R,) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R, patients predepletion may require a prolonged period of prophylaxis. [source] Acute Cellular Rejection Predominated by Monocytes Is a Severe Form of Rejection in Human Renal Recipients With or Without Campath-1H (Alemtuzumab) Induction TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2005Ping L. Zhang Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a ,pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment. [source] Alemtuzumab in the reversal of encephalopathy associated with hypereosinophilic syndromeBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2009Guilherme Fleury Perini No abstract is available for this article. [source] Routine clinical use of alemtuzumab in patients with heavily pretreated B-cell chronic lymphocytic leukemia,,CANCER, Issue 10 2006A nation-wide retrospective study in Austria Abstract BACKGROUND. In previous studies, alemtuzumab demonstrated considerable activity in patients with previously treated B-cell chronic lymphocytic leukemia (CLL), including fludarabine-refractory disease. In this retrospective study, the authors evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced, previously treated CLL who received treatment in the routine clinical setting. METHODS. Data were collected from 115 consecutive patients who received alemtuzumab therapy at 25 participating centers in Austria. Patients received a median of 3 prior lines of therapy (range, 1,11 prior lines of therapy), and 59% had fludarabine-refractory disease. Alemtuzumab was administered intravenously or subcutaneously with a planned schedule of 30 mg 3 times per week for up to 12 weeks. Patients received valacyclovir and trimethoprim/sulfamethoxazole for antiinfective prophylaxis. RESULTS. The overall response rate was 23%, with complete responses achieved in 5% of patients. Stable disease (SD) was achieved in 36% of patients. After a median follow-up of 17.5 months, the median overall survival (OS) was 20.2 months for all patients. A multivariate Cox regression analysis that included pretreatment baseline characteristics, response to therapy, and cumulative dose of alemtuzumab indicated that bulky lymphadenopathy, the administration of ,3 previous therapies, and lack of response to alemtuzumab remained significant independent risk factors for inferior OS. The median OS had not been reached for responding patients. The median OS was 29.5 months for patients with SD and 10.8 months for patients with progressive disease. CONCLUSIONS. The broad use of alemtuzumab in the routine clinical practice setting is feasible and active in unselected patients with pretreated CLL, and the current results confirmed the activity and safety of this agent, as reported in previously published clinical studies. Cancer 2006. © 2006 American Cancer Society. [source] Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemiaCANCER, Issue 12 2003Susan M. O'Brien M.D. Abstract BACKGROUND The objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti-CD52 monoclonal antibody, in patients with B-cell chronic lymphocytic leukemia and residual disease after chemotherapy. METHODS Forty-one patients received alemtuzumab 3 times weekly for 4 weeks. The first 24 patients received 10 mg per dose, and the next 17 patients received 30 mg. All patients received infection prophylaxis during therapy and for 2 months after treatment. RESULTS The overall response rate was 46%, including 39% of patients who received the 10 mg dose and responded versus 56% of the patients who received the 30 mg dose. The major reason for failure to respond was the presence of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of 29 patients (38%) achieved a molecular disease remission. The median time to disease progression had not been reached in responders with a median follow-up of 18 months. Six patients remained in disease remission between 24,38 months after therapy. Infusion-related events were common with the initial doses, but all such events were NCI Common Toxicity Criteria Grade 1,2. Infections were reported to occur in 15 patients (37%), and 9 of these infections were reactivation of cytomegalovirus. Three patients developed Epstein,Barr virus positive, large cell lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin. CONCLUSIONS Alemtuzumab produced significant responses in patients with residual disease after chemotherapy. Bone marrow disease was eradicated more frequently than lymph node disease, and molecular disease remissions were achieved. A randomized trial comparing alemtuzumab with observation after chemotherapy is indicated. Cancer 2003;98:2657,63. © 2003 American Cancer Society. [source] The clinical and epidemiological burden of chronic lymphocytic leukaemiaEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2004A. REDAELLI phd director of global outcomes research-oncology The purpose of this literature review was to identify and summarize published studies describing the epidemiology and management of chronic lymphocytic leukaemia (CLL). Chronic lymphocytic leukaemia represents 22,30% of all leukaemia cases with a worldwide incidence projected to be between <,1 and 5.5 per 100 000 people. Australia, the USA, Ireland and Italy have the highest CLL incidence rates. Chronic lymphocytic leukaemia presents in adults, at higher rates in males than in females and in whites than in blacks. Median age at diagnosis is 64,70 years. Five-year survival rate in the USA is 83% for those <,65 years old and 68% for those 65 + years old. Hereditary and genetic links have been noted. Persons with close relatives who have CLL have an increased risk of developing it themselves. No single environmental risk factor has been found to be predictive for CLL. Patients are usually diagnosed at routine health care visits because of elevated lymphocyte counts. The most common presenting symptom of CLL is lymphadenopathy, while difficulty exercising and fatigue are common complaints. Most patients do not receive treatment after initial diagnosis unless presenting with clear pathologic conditions. Pharmacological therapy may consist of monotherapy or combination therapy involving glucocorticoids, alkylating agents, and purine analogs. Fludarabine may be the most effective single drug treatment currently available. Combination therapy protocols have not been shown to be more effective than fludarabine alone. As no cure is yet available, a strong unmet medical need exists for innovative new therapies. Experimental treatments under development include allogeneic stem cell transplant, mini-allogeneic transplants, and monoclonal antibodies (e.g. alemtuzumab against CD52; rituximab against CD20). [source] Prolymphocytic leukaemia of B- and T-cell subtype: a state-of-the-art paperEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2008M. Dungarwalla Abstract Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite recent advances in immunophenotyping and molecular cytogenetics, leading to a better understanding of the underlying cell biology of the prolymphocytic leukaemias, prognosis for these patients remains poor. Purine analogues and monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia although further studies are warranted. Monoclonal antibody therapy with alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia (T-PLL) but responses are still transient and further disease progression is inevitable. While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant. [source] Atypical lymphocytic lobular panniculitisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2004Cynthia M. Magro Background:, Although subcutaneous T-cell lymphoma (SCTCL) is considered an aggressive form of lymphoma, some patients manifest a long waxing and waning phase unaccompanied by constitutional symptoms. Methods:, Twelve patients were prospectively encountered, presenting with a lymphocytic panniculitis accompanied by lymphoid atypia, although not fulfilling criteria for SCTCL. Clinical, histologic, phenotypic, and genotypic analyses were conducted. Results:, There were five men, one boy, and six women; none had symptoms compatible with lupus erythematosus or aggressive SCTCL. All but two had a waxing and waning course of years. Four patients had periodic cytopenias accompanied by fevers. While responding somewhat to prednisone, the lesions relapsed. In one patient, treatment with alemtuzumab (CAMPATH-1) led to complete lesional resolution with no recurrence. Light microscopy showed expansion of the interstices of the fat lobule by mildly atypical lymphocytes of the CD4 subset in 10 biopsies from eight patients; in the other four patients, there was an increase in CD8 lymphocytes. There was diminished expression of CD5 and/or CD7 in the majority of biopsies. Ten of 13 biopsies showed clonal T-cell receptor-, rearrangements. Conclusions:, We apply the term atypical lymphocytic lobular panniculitis to this distinctive form of lymphocytic panniculitis manifesting this light microscopic, phenotypic, and genotypic profile. [source] BK virus nephropathy after allogeneic stem cell transplantation: A case report and literature review,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2009Lazaros J. Lekakis Polyomaviruses are increasingly recognized as important human pathogens. Among those, BK virus has been identified as the main cause of polyomavirus-associated nephropathy (PVAN), a major cause of renal allograft failure. PVAN has also been well described in the setting of non-renal solid organ transplantation. The reports of PVAN after hematopoietic stem cell transplantation (HCT) are surprisingly very few. Here, we describe a patient with treatment-related myelodysplastic syndrome who received an unrelated donor HCT after ablative conditioning and in vivo T cell depletion with alemtuzumab. He developed a biopsy-proven BK nephropathy, which contributed to his renal failure. Leflunomide as well as cidofovir were given at different times, both in combination with intravenous immunoglobulin. Both treatments were effective in reducing the BK viral load, the cystitis symptoms and both stabilized but did not really improved the renal function. The patient was still dialysis-dependent when he died from Pseudomonas sepsis 13 months after HCT. A critical review of the literature and the treatment modalities for post-HCT PVAN are provided. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] Impact of alemtuzumab as conditioning regimen component on transplantation outcomes in case of CMV-seropositive recipients and donorsAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2008Yee Soo Chae We studied the incidence of cytomegalovirus (CMV) infection, clinical outcomes, and complications in 39 recipients of alemtuzumab-containing conditioning-stem cell transplantation, who were classified into two groups based on the median dose (35 mg) of alemtuzumab. All the recipients and donors were CMV-seropositive before transplantation. The median survival duration was 321 days (range, 46,1098 days) and the 2-year survival rate was 47.8%. The probability of nonrelapse mortality at 100 days and 2 years was 14.6% and 31.2%, respectively. The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) at Day 100 was 21.8%. The overall incidence of chronic GVHD (cGVHD) was 28.6%, including a 17.9% incidence of extensive cGVHD. The cumulative incidence of CMV antigenemia was 68.0%. There were no statistical differences in the engraftment, acute and cGVHD, relapse, CMV antigenemia, and overall survival (OS) between the two groups. Yet, the nonrelapse mortality (NRM) was significantly lower for the low-dose group (5.9% vs. 51.7%, P = 0.010). The present study showed that alemtuzumab was effective for GVHD prevention, yet caused a relatively high incidence of CMV antigenemia, regardless of the dose. Thus, a low dose of alemtuzumab (, 35 mg) would seem to be preferable in an allogeneic SCT setting when both the recipient and the donor are CMV seropositive. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Refractory idiopathic pure red cell aplasia complicated by immune thrombocytopenia successfully treated with subcutaneous alemtuzumabAMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2008Dat C. Pham No abstract is available for this article. [source] EBV negative Richter's syndrome from a coexistent clone after salvage treatment with alemtuzumab in a CLL patientAMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2006Ann Janssens Abstract Transformation of B cell chronic lymphocytic leukemia (B-CLL) to large cell lymphoma or Hodgkin's disease is known as a Richter's syndrome (RS). According to the literature, 1,10% of B-CLL patients develop this high-grade lymphoid malignancy. The relationship between the immunosuppressive effect of nucleoside analogues (NA) and monoclonal antibodies and the development of large cell transformation still remains a controversial issue. We describe a CLL patient who developed a large B cell lymphoma 94 months after diagnosis and 3 months after the start of alemtuzumab. The CLL immunophenotype was retained by the transforming cells although a different light chain was expressed. Molecular analysis of the immunoglobulin heavy chain confirmed that the CLL and the RS had a different clonal origin. Subsequent molecular analyses of stored samples showed that the clone with transforming capacity already appeared two years before the clinical appearance of the RS. We hypothesize that alemtuzumab promoted the uncontrolled growth of the latest clone by eradicating the initial B-CLL clone efficiently, and by inducing a strong T cell depletion with consequent impairment of the immunosurveillance. We also ruled out that the RS was EBV driven. In conclusion, we report a case of EBV negative RS after alemtuzumab as salvage therapy. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] CD52 expression in hairy cell leukemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2003Michael M. Quigley Abstract Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder characterized by splenomegaly, pancytopenia, and circulating atypical lymphocytes with circumferential cytoplasmic projections. Although uncommon, HCL cases refractory to standard therapy occur, and effective alternatives are limited. There is evolving literature supporting monoclonal antibody therapy in the treatment of B-cell lymphoid malignancies, including anti-CD52 (Campath-1H, alemtuzumab). We have examined nine cases of HCL and one case of HCL variant by flow cytometry for CD52 expression. All cases expressed CD52 antigen in 92,100% of the malignant cells. The demonstration of CD52 antigen expression on HCL cells provides the rationale for the use of alemtuzumab in refractory HCL. Am. J. Hematol. 74:227,230, 2003. © 2003 Wiley-Liss, Inc. [source] Investigation of Lymphocyte Depletion and Repopulation Using Alemtuzumab (Campath-1H) in Cynomolgus MonkeysAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010D. J. Van Der Windt As the target CD52 molecule is expressed on erythrocytes of most nonhuman primate strains, using alemtuzumab in these species would cause massive hemolysis. Six cynomolgus monkeys of Indonesian origin, screened by agglutination assay for absence of CD52 on erythrocytes, were administered alemtuzumab in a cumulative dose to a maximum of 60 mg/kg. In two monkeys, mycophenolate mofetil (MMF) was added as maintenance therapy. Complete depletion of T and B lymphocytes (>99.5%) was achieved with 20 mg/kg alemtuzumab and was more profound than in monkeys treated with antithymocyte globulin (n = 5), as quantified by flow cytometry. Repopulation was suppressed by weekly injections of 10 mg/kg. Without MMF, repopulation of CD20+B cells and CD8+T cells was complete within 2 and 3 months, respectively, and repopulation of CD4+T cells was 67% after 1 year. MMF significantly delayed CD4+T-cell repopulation. Among repopulating CD4+ and CD8+ T cells, a phenotypic shift was observed from CD45RAhiCD62Lhi naïve cells toward CD45RAloCD62Llo effector memory cells. In lymph nodes, the depletion of naïve cells was more profound than of memory cells, which may have initiated a proliferation of memory cells. This model offers opportunities to investigate lymphocyte depletion/repopulation phenomena, as well as the efficacy of alemtuzumab in preclinical transplantation models. [source] Alemtuzumab Induction Prior to Cardiac Transplantation with Lower Intensity Maintenance Immunosuppression: One-Year OutcomesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010J. J. Teuteberg Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1,3 (8.5 vs. 12.9), month 4,6 (10.2 vs. 13.0), month 7,9 (10.2 vs. 11.9) and month 10,12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids. [source] Homeostatic Repopulation by CD28,CD8+ T Cells in Alemtuzumab-Depleted Kidney Transplant Recipients Treated With Reduced ImmunosuppressionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008P. Trzonkowski Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation. We found that after alemtuzumab induction the recovery of CD8+ T cells was much faster than that of CD4+ T cells. It was complete 6 months posttransplant while CD4+ T cells did not fully recover even 15 months posttransplant. Repopulating CD8+ T cells were mainly of immunosenescent CD28,CD8+ phenotype. In a series of in vitro experiments we showed that CD28,CD8+ T cells might suppress proliferation of CD4+ T cells. There were three successfully treated acute rejections during the study (first at +70 day, two others +12 months) that occurred in patients with the lowest level of CD28,CD8+ T cells. We hypothesize that expanded CD28,CD8+ T cells might compete for ,immune space' with CD4+ T cells suppressing their proliferation and therefore delaying CD4+ T-cells recovery. This delay might be associated with the clinical outcome as CD4+ T cells, notably CD4+ T effector memory cells, were shown to be associated with rejection. [source] Recovery of Functional Memory T Cells in Lung Transplant Recipients Following Induction Therapy with AlemtuzumabAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2007A. Zeevi Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow® and T Cell MemoryÔ, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4,5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R,) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R, patients predepletion may require a prolonged period of prophylaxis. [source] Immunocompetent T-Cells with a Memory-Like Phenotype are the Dominant Cell Type Following Antibody-Mediated T-Cell DepletionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2005Jonathan P. Pearl T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We therefore studied patients undergoing profound T-cell depletion with alemtuzumab or rabbit anti-thymocyte globulin following renal transplantation, evaluating the phenotype and functional characteristics of their residual cells. Naïve T cells and T cells with potential regulatory function (CD4+CD25+) were not prevalent following aggressive depletion. Rather, post-depletion T cells were of a single phenotype (CD3+CD4+CD45RA-CD62L-CCR7-) consistent with depletion-resistant effector memory T cells that expanded in the first month and were uniquely prevalent at the time of rejection. These cells were resistant to steroids, deoxyspergualin or sirolimus in vitro, but were calcineurin-inhibitor sensitive. These data demonstrate that therapeutic depletion begets a limited population of functional memory-like T cells that are easily suppressed with certain immunosuppressants, but cannot be considered uniquely pro-tolerant. [source] Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy-induced lymphopenia: Twelve-year outcomesARTHRITIS & RHEUMATISM, Issue 2 2008Alice R. Lorenzi Objective To assess immunologically relevant outcomes in a cohort of rheumatoid arthritis (RA) patients with prolonged therapy-induced lymphopenia. Methods Morbidity (infection or malignancy) and mortality were assessed in 53 RA patients who were treated with the lymphocytotoxic monoclonal antibody alemtuzumab between 1991 and 1994. Data were obtained by interview, medical record review, and Office for National Statistics mortality monitoring. Lymphocyte subsets were enumerated by flow cytometry. A retrospective, matched-cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database of patients with rheumatic disorders. Results Lymphopenia persisted in the patients: median CD3+CD4+, CD3+CD8+, CD19+, and CD56+ lymphocyte counts measured at a median followup of 11.8 years from the first administration of alemtuzumab were 0.50 × 109/liter, 0.26 × 109/liter, 0.11 × 109/liter, and 0.09 × 109/liter, respectively. Twenty-seven of 51 cases and 46 of 101 controls with available data had died, yielding a mortality rate ratio of 1.20 (95% confidence interval 0.72,1.98). Causes of death were similar to those that would be expected in a hospital-based RA cohort. No opportunistic infections were noted, and only 3 infections were documented following 36 elective orthopedic procedures. Conclusion Despite continued lymphopenia 11.8 years after therapy, our patient cohort did not exhibit excess mortality or unusual infection-related morbidity, and surgery was well tolerated. These data should be reassuring for clinicians and patients who are considering lymphocytotoxic or other immunomodulatory therapy for RA. [source] Cutaneous cryptococcosis with alemtuzumab in a patient treated for chronic lymphocytic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2007Marie-Sarah Dilhuydy No abstract is available for this article. [source] | |||||||||||||||||||||||||