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Claire Dearden - One of the best experts on this subject based on the ideXlab platform.
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t cell Prolymphocytic Leukemia
Hematology-oncology Clinics of North America, 2017Co-Authors: Amit Sud, Claire DeardenAbstract:T-cell Prolymphocytic Leukemia (T-PLL) is a rare and aggressive T-cell malignancy. T-PLL can be distinguished from other lymphoid diseases by the evaluation and integration of clinical features, morphology, immunophenotyping, cytogenetics, and molecular features. The current therapeutic approach relies on immunotherapy followed by a hematopoietic stem cell transplant in selected cases. Clinical outcomes are generally poor, although insights from genomic and molecular studies may increase our understanding of this disease, with the promise of additional effective therapeutic options.
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b and t cell Prolymphocytic Leukemia antibody approaches
Hematology, 2012Co-Authors: Claire DeardenAbstract:B- and T-cell subtypes of Prolymphocytic Leukemia (PLL) are rare, aggressive lymphoid malignancies with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features. Prognosis for these patients remains poor, with short survival times and no curative therapy. The advent of mAbs has improved treatment options. In B-PLL, rituximab-based combination chemoimmunotherapy is effective in fitter patients. TP53 abnormalities are common and, as for chronic lymphocytic Leukemia, these patients should generally be managed using an alemtuzumab-based therapy. Currently, the best treatment for T-PLL is IV alemtuzumab, which has resulted in very high response rates of more than 90% when given as frontline treatment and a significant improvement in survival. Consolidation of remissions with autologous or allogeneic stem cell transplantation further prolongs survival times, and the latter may offer potential cure. The role of allogeneic transplantation with nonmyeloablative conditioning needs to be explored further in both T- and B-PLL to broaden the patient eligibility for what may be a curative treatment.
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how i treat Prolymphocytic Leukemia
Blood, 2012Co-Authors: Claire DeardenAbstract:T- and B-cell subtypes of Prolymphocytic Leukemia (PLL) are rare, aggressive lymphoid malignancies with characteristic morphologic, immunophenotypic, cytogenetic, and molecular features. Recent studies have highlighted the role of specific oncogenes, such as TCL-1, MTCP-1, and ATM in the case of T-cell and TP53 mutations in the case of B-cell Prolymphocytic Leukemia. Despite the advances in the understanding of the biology of these conditions, the prognosis for these patients remains poor with short survival and no curative therapy. The advent of monoclonal antibodies has improved treatment options. Currently, the best treatment for T-PLL is intravenous alemtuzumab, which has resulted in very high response rates of more than 90% when given as first-line treatment and a significant improvement in survival. Consolidation of remissions with autologous or allogeneic stem cell transplantation further prolongs survival, and the latter may offer potential cure. In B-PLL, rituximab-based combination chemo-immunotherapy is effective in fitter patients. TP53 abnormalities are common and, as for chronic lymphocytic Leukemia, these patients should be managed using an alemtuzumab-based therapy. The role of allogeneic transplant with nonmyeloablative conditioning needs to be explored further in both T- and B-cell PLL to broaden the patient eligibility for what may be a curative treatment.
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hematopoietic stem cell transplantation in t Prolymphocytic Leukemia a retrospective study from the european group for blood and marrow transplantation and the royal marsden consortium
Leukemia, 2012Co-Authors: Wieslaw Wiktorjedrzejczak, Claire Dearden, L C De Wreede, A Van Biezen, L Brinch, Veronique Leblond, Mats Brune, Liisa Volin, Majid Kazmi, Arnon NaglerAbstract:T-Prolymphocytic Leukemia (T-PLL) has a very poor prognosis with conventional immunochemotherapy. Incidental reports suggest that allogeneic hematopoietic stem cell transplantation (allo-HSCT) might have a role in this disease. Therefore, the purpose of the present study was to analyze the outcome of transplants for T-PLL registered with the European Group for Blood and Marrow Transplantation database and the Royal Marsden Consortium. Eligible were 41 patients with a median age of 51 (24-71) years; median time from diagnosis to treatment was 12 months, and in complete remission (CR) (11), partial remission (PR) (12), stable or progressive disease (13) and unknown in 5 patients. A total of 13 patients (31%) received reduced-intensity conditioning. Donors were HLA-identical siblings in 21 patients, matched unrelated donors in 20 patients. With a median follow-up of surviving patients of 36 months, 3-year relapse-free survival (RFS) and OS was 19% (95% CI, 6-31%) and 21% (95% CI, 7-34%), respectively. Multivariate analysis identified TBI and a short interval between diagnosis and HSCT as factors associated with favorable RFS. Three-year non relapse mortality and relapse incidence were each 41% with the majority of relapses occurring within the first year. These data indicate that allo-HSCT may provide effective disease control in selected patients with T-PLL.
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alemtuzumab therapy in t cell Prolymphocytic Leukemia comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route
Blood, 2011Co-Authors: Claire Dearden, Amit Khot, Monica Else, Mike Hamblin, Effie Grand, Ashok Roy, Saman Hewamana, Estella Matutes, Daniel CatovskyAbstract:Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell Prolymphocytic Leukemia (T-PLL). Alemtuzumab given intravenously as first-line treatment in 32 patients resulted in an overall response rate of 91% with 81% complete responses. Studies in B-cell chronic lymphocytic Leukemia have shown subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab. The UKCLL05 pilot study examined the efficacy and toxicity of this more convenient method of administration in 9 previously untreated patients with T-PLL. Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9 patients (22%) died while on treatment. Recruitment was terminated because of these poor results. After rescue therapy with intravenous alemtuzumab and/or pentostatin, median progression-free survival and overall survival were similar to the intravenous group. Alemtuzumab delivered intravenously, but not subcutaneously, remains the treatment of choice for previously untreated T-PLL.
Estella Matutes - One of the best experts on this subject based on the ideXlab platform.
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alemtuzumab therapy in t cell Prolymphocytic Leukemia comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route
Blood, 2011Co-Authors: Claire Dearden, Amit Khot, Monica Else, Mike Hamblin, Effie Grand, Ashok Roy, Saman Hewamana, Estella Matutes, Daniel CatovskyAbstract:Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell Prolymphocytic Leukemia (T-PLL). Alemtuzumab given intravenously as first-line treatment in 32 patients resulted in an overall response rate of 91% with 81% complete responses. Studies in B-cell chronic lymphocytic Leukemia have shown subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab. The UKCLL05 pilot study examined the efficacy and toxicity of this more convenient method of administration in 9 previously untreated patients with T-PLL. Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9 patients (22%) died while on treatment. Recruitment was terminated because of these poor results. After rescue therapy with intravenous alemtuzumab and/or pentostatin, median progression-free survival and overall survival were similar to the intravenous group. Alemtuzumab delivered intravenously, but not subcutaneously, remains the treatment of choice for previously untreated T-PLL.
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b cell Prolymphocytic Leukemia and chronic lymphocytic Leukemia have distinctive gene expression signatures
Leukemia, 2009Co-Authors: I Del Giudice, Daniel Catovsky, Nnenna Osuji, Tim Dexter, Vasantha Britobabapulle, N Parryjones, Sabina Chiaretti, Monica Messina, Gareth J Morgan, Estella MatutesAbstract:B-cell Prolymphocytic Leukemia and chronic lymphocytic Leukemia have distinctive gene expression signatures
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igvh genes mutation and usage zap 70 and cd38 expression provide new insights on b cell Prolymphocytic Leukemia b pll
Leukemia, 2006Co-Authors: Estella Matutes, I Del Giudice, Nnenna Osuji, Vasantha Britobabapulle, N Parryjones, Zadie Davis, Alison Morilla, David Oscier, Daniel CatovskyAbstract:IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell Prolymphocytic Leukemia (B-PLL)
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histopathology of the spleen in t cell large granular lymphocyte Leukemia and t cell Prolymphocytic Leukemia a comparative review
The American Journal of Surgical Pathology, 2005Co-Authors: Nnenna Osuji, Estella Matutes, Daniel Catovsky, Irvin A Lampert, Andrew WotherspoonAbstract:We review retrospectively the spleen histology in 8 patients with T-cell large granular lymphocyte (LGL) Leukemia and 4 with T-cell Prolymphocytic Leukemia (T-PLL) to identify characteristic patterns of involvement and to distinguish such patterns from those described in other low grade B- and T-cell malignancies. Moderate splenic enlargement with red pulp expansion due to lymphocytic infiltration was characteristic of LGL Leukemia. Abnormal lymphocytes expressed cytotoxic granule proteins and were consistently CD45RO and CD5 negative in contrast to normal red pulp T cells. This infiltration respected anatomic boundaries with encroachment but no invasion of white pulp areas. Unlike in hairy cell Leukemia, the main differential diagnosis for red pulp lymphocytosis, the white pulp was not only preserved in T-cell LGL Leukemia but showed germinal center hyperplasia with expansion of the mantle zones. By comparison, T-PLL spleens showed marked red pulp lymphoid infiltration by medium-sized cells with irregular nuclei and prominent eosinophilic nucleoli. T-PLL lymphocytes, unlike LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp areas. T-cell prolymphocytes did not express cytotoxic granule proteins or NK-cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+, CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-. Expression of CD4 and CD8 in these cells mirrored that of circulating T-PLL cells. These observations on the morphologic and immunohistochemical appearances of the spleen in T-cell LGL Leukemia and T-PLL may aid diagnosis of these uncommon T-cell disorders, particularly T-cell LGL Leukemia, where presentation may be cryptic and where unique pathognomonic features, are absent.
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histopathology of the spleen in t cell large granular lymphocyte Leukemia and t cell Prolymphocytic Leukemia a comparative review
The American Journal of Surgical Pathology, 2005Co-Authors: Nnenna Osuji, Estella Matutes, Daniel Catovsky, Irvin A Lampert, Andrew WotherspoonAbstract:We review retrospectively the spleen histology in 8 patients with T-cell large granular lymphocyte (LGL) Leukemia and 4 with T-cell Prolymphocytic Leukemia (T-PLL) to identify characteristic patterns of involvement and to distinguish such patterns from those described in other low grade B- and T-cell malignancies. Moderate splenic enlargement with red pulp expansion due to lymphocytic infiltration was characteristic of LGL Leukemia. Abnormal lymphocytes expressed cytotoxic granule proteins and were consistently CD45RO and CD5 negative in contrast to normal red pulp T cells. This infiltration respected anatomic boundaries with encroachment but no invasion of white pulp areas. Unlike in hairy cell Leukemia, the main differential diagnosis for red pulp lymphocytosis, the white pulp was not only preserved in T-cell LGL Leukemia but showed germinal center hyperplasia with expansion of the mantle zones. By comparison, T-PLL spleens showed marked red pulp lymphoid infiltration by medium-sized cells with irregular nuclei and prominent eosinophilic nucleoli. T-PLL lymphocytes, unlike LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp areas. T-cell prolymphocytes did not express cytotoxic granule proteins or NK-cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+, CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-. Expression of CD4 and CD8 in these cells mirrored that of circulating T-PLL cells. These observations on the morphologic and immunohistochemical appearances of the spleen in T-cell LGL Leukemia and T-PLL may aid diagnosis of these uncommon T-cell disorders, particularly T-cell LGL Leukemia, where presentation may be cryptic and where unique pathognomonic features, are absent.
Daniel Catovsky - One of the best experts on this subject based on the ideXlab platform.
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alemtuzumab therapy in t cell Prolymphocytic Leukemia comparing efficacy in a series treated intravenously and a study piloting the subcutaneous route
Blood, 2011Co-Authors: Claire Dearden, Amit Khot, Monica Else, Mike Hamblin, Effie Grand, Ashok Roy, Saman Hewamana, Estella Matutes, Daniel CatovskyAbstract:Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell Prolymphocytic Leukemia (T-PLL). Alemtuzumab given intravenously as first-line treatment in 32 patients resulted in an overall response rate of 91% with 81% complete responses. Studies in B-cell chronic lymphocytic Leukemia have shown subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab. The UKCLL05 pilot study examined the efficacy and toxicity of this more convenient method of administration in 9 previously untreated patients with T-PLL. Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9 patients (22%) died while on treatment. Recruitment was terminated because of these poor results. After rescue therapy with intravenous alemtuzumab and/or pentostatin, median progression-free survival and overall survival were similar to the intravenous group. Alemtuzumab delivered intravenously, but not subcutaneously, remains the treatment of choice for previously untreated T-PLL.
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b cell Prolymphocytic Leukemia and chronic lymphocytic Leukemia have distinctive gene expression signatures
Leukemia, 2009Co-Authors: I Del Giudice, Daniel Catovsky, Nnenna Osuji, Tim Dexter, Vasantha Britobabapulle, N Parryjones, Sabina Chiaretti, Monica Messina, Gareth J Morgan, Estella MatutesAbstract:B-cell Prolymphocytic Leukemia and chronic lymphocytic Leukemia have distinctive gene expression signatures
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igvh genes mutation and usage zap 70 and cd38 expression provide new insights on b cell Prolymphocytic Leukemia b pll
Leukemia, 2006Co-Authors: Estella Matutes, I Del Giudice, Nnenna Osuji, Vasantha Britobabapulle, N Parryjones, Zadie Davis, Alison Morilla, David Oscier, Daniel CatovskyAbstract:IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell Prolymphocytic Leukemia (B-PLL)
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histopathology of the spleen in t cell large granular lymphocyte Leukemia and t cell Prolymphocytic Leukemia a comparative review
The American Journal of Surgical Pathology, 2005Co-Authors: Nnenna Osuji, Estella Matutes, Daniel Catovsky, Irvin A Lampert, Andrew WotherspoonAbstract:We review retrospectively the spleen histology in 8 patients with T-cell large granular lymphocyte (LGL) Leukemia and 4 with T-cell Prolymphocytic Leukemia (T-PLL) to identify characteristic patterns of involvement and to distinguish such patterns from those described in other low grade B- and T-cell malignancies. Moderate splenic enlargement with red pulp expansion due to lymphocytic infiltration was characteristic of LGL Leukemia. Abnormal lymphocytes expressed cytotoxic granule proteins and were consistently CD45RO and CD5 negative in contrast to normal red pulp T cells. This infiltration respected anatomic boundaries with encroachment but no invasion of white pulp areas. Unlike in hairy cell Leukemia, the main differential diagnosis for red pulp lymphocytosis, the white pulp was not only preserved in T-cell LGL Leukemia but showed germinal center hyperplasia with expansion of the mantle zones. By comparison, T-PLL spleens showed marked red pulp lymphoid infiltration by medium-sized cells with irregular nuclei and prominent eosinophilic nucleoli. T-PLL lymphocytes, unlike LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp areas. T-cell prolymphocytes did not express cytotoxic granule proteins or NK-cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+, CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-. Expression of CD4 and CD8 in these cells mirrored that of circulating T-PLL cells. These observations on the morphologic and immunohistochemical appearances of the spleen in T-cell LGL Leukemia and T-PLL may aid diagnosis of these uncommon T-cell disorders, particularly T-cell LGL Leukemia, where presentation may be cryptic and where unique pathognomonic features, are absent.
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histopathology of the spleen in t cell large granular lymphocyte Leukemia and t cell Prolymphocytic Leukemia a comparative review
The American Journal of Surgical Pathology, 2005Co-Authors: Nnenna Osuji, Estella Matutes, Daniel Catovsky, Irvin A Lampert, Andrew WotherspoonAbstract:We review retrospectively the spleen histology in 8 patients with T-cell large granular lymphocyte (LGL) Leukemia and 4 with T-cell Prolymphocytic Leukemia (T-PLL) to identify characteristic patterns of involvement and to distinguish such patterns from those described in other low grade B- and T-cell malignancies. Moderate splenic enlargement with red pulp expansion due to lymphocytic infiltration was characteristic of LGL Leukemia. Abnormal lymphocytes expressed cytotoxic granule proteins and were consistently CD45RO and CD5 negative in contrast to normal red pulp T cells. This infiltration respected anatomic boundaries with encroachment but no invasion of white pulp areas. Unlike in hairy cell Leukemia, the main differential diagnosis for red pulp lymphocytosis, the white pulp was not only preserved in T-cell LGL Leukemia but showed germinal center hyperplasia with expansion of the mantle zones. By comparison, T-PLL spleens showed marked red pulp lymphoid infiltration by medium-sized cells with irregular nuclei and prominent eosinophilic nucleoli. T-PLL lymphocytes, unlike LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp areas. T-cell prolymphocytes did not express cytotoxic granule proteins or NK-cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+, CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-. Expression of CD4 and CD8 in these cells mirrored that of circulating T-PLL cells. These observations on the morphologic and immunohistochemical appearances of the spleen in T-cell LGL Leukemia and T-PLL may aid diagnosis of these uncommon T-cell disorders, particularly T-cell LGL Leukemia, where presentation may be cryptic and where unique pathognomonic features, are absent.
Steven Coutre - One of the best experts on this subject based on the ideXlab platform.
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a pediatric case of t cell Prolymphocytic Leukemia
Pediatric Blood & Cancer, 2015Co-Authors: Bryan Mitton, Steven Coutre, Jennifer Willert, Krysta Schlis, Matthew H Porteus, Sandhya Kharbanda, Rajni AgarwalhashmiAbstract:T-cell Prolymphocytic Leukemia (T-PLL) is a rare entity, and to date has never been reported in children. Here, we describe the first pediatric case of T-PLL in a 16-year old male and review his clinical course through treatment. He underwent therapy with alemtuzumab and pentostatin, which was successful in inducing initial remission. He then underwent an allogeneic matched sibling stem cell transplant following a myeloablative conditioning regimen and remains disease-free 1.5 years after diagnosis. Pediatr Blood Cancer 2015;62:1061–1062. © 2014 Wiley Periodicals, Inc.
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cytomegalovirus viremia during campath 1h therapy for relapsed and refractory chronic lymphocytic Leukemia and Prolymphocytic Leukemia
Clinical Lymphoma Myeloma & Leukemia, 2002Co-Authors: Dorothy D Nguyen, Thai M Cao, Kathleen Dugan, Stacey A Starcher, Lenn R Fechter, Steven CoutreAbstract:Campath-1H is effective therapy for patients with relapsed and refractory chronic lymphocytic Leukemia (CLL) and Prolymphocytic Leukemia (PLL), but it is associated with profound lymphopenia and deficiencies in cell-mediated immunity. We report the incidence of cytomegalovirus (CMV) viremia in 34 patients treated with Campath-1H for relapsed or refractory CLL and PLL. All patients received infection prophylaxis during therapy and continuing for at least 2 months following Campath-1H. Five patients (15%) developed CMV viremia at a median of 28 days (range, 20-30 days) after the first dose of Campath-1H. The median CMV viral load was 860/mL (range, 420-2100/mL), as determined by quantitative plasma polymerase chain reaction (PCR). All 5 patients had a temperature > 38.5 degrees C, normal chest radiographs, normal liver function tests, and negative bacterial blood cultures with no clinical evidence of CMV disease at the time of presentation with CMV viremia. The median absolute neutrophil count (ANC) was 740/ microL (range, 340-1600/ microL), and the median absolute lymphocyte count (ALC) was 16/microL (range, 11-169/ microL) for the 5 patients at the time of CMV viremia. All 5 patients received ganciclovir therapy followed by prompt fever resolution and clearance of CMV viremia by plasma PCR. By univariate regression analysis, the following were not risk factors for CMV viremia: age, number of prior regimens, prior rituximab therapy, prior splenectomy, modified Rai stage at Campath-1H therapy (low/intermediate vs. high), ANC, and ALC; although, there was a trend towards significance for prior rituximab therapy (P = 0.07). Cytomegalovirus viremia may be a significant infectious complication during Campath-1H therapy and should be investigated further in future studies.
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campath 1h treatment of t cell Prolymphocytic Leukemia in patients for whom at least one prior chemotherapy regimen has failed
Journal of Clinical Oncology, 2002Co-Authors: M J Keating, B Cazin, Steven Coutre, R Birhiray, Tibor Kovacsovics, W Langer, Brian Leber, T Maughan, G Tjonnfjord, M BekraddaAbstract:PURPOSE: We conducted a retrospective analysis to evaluate the safety and efficacy of Campath-1H, an anti-CD52 humanized monoclonal antibody, in previously treated T-Prolymphocytic Leukemia (T-PLL) patients in a compassionate-use program. PATIENTS AND METHODS: Seventy-six patients with T-PLL (including four chemotherapy-naive patients) received 3, 10, and 30 mg of Campath-1H on sequential days, followed by 30 mg three times weekly, as 2-hour intravenous infusions, for 4 to 12 weeks. RESULTS: Median patient age was 60 years (range, 35 to 84). Spleen liver, lymph node, and skin involvement were present in 64%, 40%, 54%, and 18% of patients, respectively. All tested patients had CD2, CD7, CD4, and/or CD8 positivity, whereas CD5 and CD3 were positive in 98% and 96% of tested patients, respectively. The objective response rate was 51% (95% confidence interval [CI], 40% to 63%), with a 39.5% complete response (CR) rate (95% CI, 28% to 51%). The median duration of CR was 8.7 months (range, 0.13+ to 44.4), and me...
Donna Adams - One of the best experts on this subject based on the ideXlab platform.
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alemtuzumab in relapsed or refractory chronic lymphocytic Leukemia and Prolymphocytic Leukemia
Leukemia & Lymphoma, 2002Co-Authors: Steven L Mccune, Jon P Gockerman, Joseph O Moore, Carlos M Decastro, Adam J Bass, Nelson J Chao, Gwynn D Long, James J Vredenburgh, Cristina Gasparetto, Donna AdamsAbstract:Twenty-three adult patients with relapsed or refractory chronic lymphocytic Leukemia (CLL) or Prolymphocytic Leukemia (PLL) were treated for up to 12 weeks with the anti-CD52 monoclonal antibody alemtuzumab. Patients were a median of six years from diagnosis and had been treated with a median of four chemotherapy regimens (median of 24 total cycles) prior to enrollment. Fourteen patients (61%) had received prior monoclonal antibody therapy with rituximab. Adverse symptoms were primarily mild to moderate fever, rigor/chills, nausea/vomiting, or fatigue/malaise in up to 86% of patients. Patients with low blood counts at the initiation of alemtuzumab tolerated therapy well. A total of 17 patients were evaluable for disease response. Nine patients (53%) responded with complete remissions in the peripheral blood. Of these nine, five were evaluated by bone marrow biopsy with four complete responses (CR) and one partial response. Six of the nine presented with nodal disease at the start of alemtuzumab therapy wi...
