SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Leukemia & lymphoma

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Abstract Previous studies have suggested that CD30 may be expressed in diffuse large B-cell lymphomas (DLBCL). However, the prevalence of CD30+ DLBCLs and extent of CD30 expression within an individual tumor has not been fully evaluated. The aim of this study was to determine the frequency and extent of CD30 expression in DLBCLs, and explore possible relationships between CD30 expression and clinical and biologic variables. We retrospectively identified and analyzed 167 cases of CD30+ DLBCLs from our pathology archive. Twenty-one percent (95% CI: 14.8% - 27.1%) of these cases expressed CD30 and in 52% of them CD30 was positive in > 80% of tumor cells. CD30 expression was more frequent in DLBCLs with non-germinal center origin phenotype, BCL2+ DLBCLs and in patients ≤47 years old. There was significant interaction of BCL2 expression with age and subtype of DLBCL. A multivariate analysis performed in BCL2+ DLBCLs showed a higher frequency of CD30+ cases in non-GC DLBCLs (odds ratio [OR]: 6.5, 95% CI: 1.1 - 36.5) and in patients ≤47 years old (OR: 6.9, 95% CI: 1.5 - 29.5). These associations could suggest a common biologic pathogenesis. The effectiveness of anti-CD30 drugs in other lymphomas opens the possibility for its use in patients with CD30+ DLBCLs.

Concepts: Cancer, Medical statistics, B cell, Types of cancer, Lymphoma, Diffuse large B cell lymphoma, Anaplastic large cell lymphoma, B-cell lymphoma

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Abstract Over the past 3 years, ibrutinib (PCI-32765) has emerged as a breakthrough in targeted therapy for patients with certain types of B cell malignancies. Early stage clinical trials found ibrutinib to be particularly active in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), providing the rationale for ongoing Phase 3 trials. In contrast to conventional chemo-immunotherapy, ibrutinib is not myelo-suppressive, and responses are not affected by disease features that predict failure to respond to or short remission durations after chemo-immunotherapy, such as del17p. In CLL, ibrutinib characteristically causes an early redistribution of tissue-resident CLL cells into the blood, with rapid resolution of enlarged lymph nodes, along with a surge in lymphocytosis. Later, after weeks to months of continuous ibrutinib therapy, the growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients. This review discusses the discovery, preclinical and clinical development of ibrutinib, its pathophysiological basis, and outlines perspectives for future use of ibrutinib.

Concepts: Lymphocyte, Clinical trial, Cancer, Lymph node, B cell, Leukemia, Lymphoma, Pre-clinical development

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Abstracts: Curcumin and Taurine are natural products that have been used in this purpose to evaluate their therapeutic effect on the myeloid leukemic cells propagated in vitro. Sixty myeloid leukemia patients and thirty healthy volunteers were enrolled in the study. All patients groups were admitted to the medical oncology department of the National Cancer Institute, Cairo University. There were statistically significant differences between treated leukemic cells compared to normal mononuclear leukocytes in cell density, Interferon-γ and immunophenotypic characterizations mainly CD4(+), CD8(+) and CD25(+). This work highlights the possibility of using Curcumin and Taurine as a potential useful therapy in the management of patients suffering from chronic and acute myeloid leukemias.

Concepts: White blood cell, Medicine, Cancer, Bone marrow, Statistical significance, Chemotherapy, Leukemia, Acute myeloid leukemia

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Mantle cell lymphoma is a relatively rare type of non-Hodgkin lymphoma that accounts for approximately 6000 new cases per year in the USA. The median age of patients at presentation is around 65 years, and almost all patients present with stage IV disease. Over the past decade, our understanding of the molecular pathology of the disease has substantially improved. Furthermore, intensive chemotherapy treatment options were developed to improve the complete remission rates and to prolong the remission duration. More recently, several targeted agents have shown promising clinical results with good safety profiles. Future directions should focus on incorporating these novel agents in new less toxic regimens, and should also identify biomarkers that can better match patients with effective treatment strategies.

Concepts: Time, Better, Cancer, Improve, Chemotherapy, Lymphoma, Chemotherapy regimens, Mantle cell lymphoma

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The combination of lenalidomide, bortezomib and dexamethasone (RVD) has shown excellent efficacy in patients with relapsed or refractory multiple myeloma (RRMM). The aim of our study was to assess the efficacy and toxicity profile of RVD for patients with advanced RRMM. We retrospectively reviewed the records of all patients with RRMM treated with RVD between March 2009 and December 2011. Thirty patients received ≥1 full cycle of RVD. Primary endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). After a median of 5 cycles (1-16), a very good partial response (VGPR) was seen in 10%, partial response (PR) in 36.7% and stable disease (SD) in 13.3% (ORR of 46.7%). Disease progression occurred in 21 patients at a median of 3 months (range 1.41-4.59). Eight patients (26%) experienced grade ¾ adverse events, including anemia, neutropenia, muscle weakness and pneumonia. No patient experienced worsening peripheral neuropathy. Although RVD has been previously shown to be effective in RRMM, the ORR and PFS we observed were affected by very advanced disease status and heavy prior exposure to novel agents. Nevertheless, six of these patients with RRMM experienced a benefit of ≥6 months, suggesting synergism of this immunomodulatory derivative/proteasome inhibitor combination and/or re-establishment of drug sensitivity by an emergent myeloma clone.

Concepts: Multiple myeloma, Bone marrow, Thalidomide, Lenalidomide, Proteasome, Bortezomib, Dexamethasone, Spinal cord compression

28

The H97-I trial (1997-2004) for Hodgkin lymphoma at intermediate stage (HL-I) included 269 patients who were randomized to receive three or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The 197 patients who reached complete remission (CR) (73.2%, p = 0.41 between arms) received radiotherapy (RT); their 10-year progression-free survival (PFS) rate was 87.7 ± 3.0%, similar to that of the 180 patients of a historical control group (HCG) in CR after three ABVD cycles before RT. The 59 patients who reached post-ABVD partial remission (PR) received one course of intensive chemotherapy (i.v., mg/m(2), vindesine 5, adriamycin 90, BCNU 140, etoposide 600, methylprednisolone 600) before RT. In spite of this additional intensive chemotherapy, their PFS rate (78.4 ± 6.3%) remained significantly lower (p = 0.03) than that of the 197 patients who reached post-ABVD CR, and was similar to that of the 60 patients of the HCG in PR after three ABVD cycles who did not receive additional chemotherapy before RT.

Concepts: Chemotherapy, Lymphoma, Hodgkin's lymphoma, Doxorubicin, CYP3A4, ABVD, Antineoplastic drugs, Vinblastine

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Abstract Fewer than 10% of patients with myelodysplastic syndromes (MDS) are younger than 50 years. A series of 91 younger patients (median age 44 years with female prevalence) are reported and compared with elderly patients. Frequent karyotypic changes were trisomy 8 (9.8%) and monosomy 7 (5%). Twenty-three patients had occupational exposure to potential mutagens (benzene and solvents), with a male predominance, higher frequency of refractory cytopenia with multilineage dysplasia (RCMD) (52%) and higher frequency of monosomy 7 (21.7%). At a median follow-up of 72 months, 22 patients (24%) evolved to acute leukemia, with higher frequency being observed among the exposed cohort (39% vs. 19% non-exposed). Unfavorable factors for overall survival were: age > 40 years, > 5% of blasts, trilinear bone marrow involvement and intermediate-high World Health Organization Prognostic Scoring System (WPSS) risk. The present results suggest that younger MDS could be identified as a distinct subset. For patients belonging to the low/intermediate-I risk group, due to a low transformation rate, aggressive approaches should rarely be recommended.

Concepts: Cancer, Bone marrow, Syndromes, Benzene, Acute myeloid leukemia, World Health Organization, Myelodysplastic syndrome, Refractory cytopenia with multilineage dysplasia

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ABSTRACT Plasma cell dyscrasias accounts for 1% of all malignancies and 10 % of haematological malignancies. About 5% of patients with a plasma cell dyscrasia present with either solitary bone plasmacytoma (SBP) or less commonly, a soft tissue mass; extramedullary plasmacytoma (EMP) of monoclonal plasma cells. In this study we present clinical features, management and outcome of 60 patients of SP, this comprised 5.6% of 1129 patients of pasma cell dyscrasias treated over 10 year period at All India Institute of Medical Sciences. Median age was 49 years. Fifty two were SBP and 8 were EMP. Forty nine (82%) patients received radiotherapy with or without surgical excision or chemotherapy. Five year EFS and OS were 45.5% and 91% respectively. Median EFS and OS were 38 and 122 months respectively. Five year survival rate in patients who developed multiple myeloma and those who did not were 81% and 100% respectively. The median time of progression to myeloma was 21 months.

Concepts: Multiple myeloma, Medicine, Surgery, Radiation therapy, Plasma cell, Plasmacytoma, Paraprotein, Plasma cell dyscrasia

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Over the past decade, it has become increasingly clear that mantle cell lymphoma (MCL) is a more heterogeneous disease than originally recognized. Several groups have reported on a subgroup of patients with a less aggressive course than expected resulting in the term “indolent MCL”. Unlike the recognized histologic variants, the definition of indolent mantle cell lymphoma is unclear, and patients with indolent MCL are often identified only after having undergone prolonged periods of observation. In this review, we will discuss clinical and biologic features and provide a framework for the approach in identifying patients with indolent MCL.

Concepts: Cancer, Medical terms, Mantle cell lymphoma, 2004 albums, Mantle zone

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Abstract Despite recent advances in therapeutic strategies, a large proportion of patients with mantle cell lymphoma experience progression after first-line treatment. Several attempts have been performed for assessing the role of different therapies for the treatment of patients with relapsed/refractory MCL; however, a consensus on the optimal therapeutic strategy for each single patient has not been reached. Overall, clinical evidence from phase II studies show that high-dose containing regimens, stem cell transplantation, and different biological agents all have promising activity with acceptable safety profiles. Therefore, these therapies can represent suitable treatment options for patients with refractory/relapsed MCL. Among different biological agents, at present only temsirolimus was tested in a phase III study. This review discusses available evidence on the management of refractory/relapsed MCL as discussed during a consensus meeting on the current treatment strategies for MCL.

Concepts: Medicine, Clinical trial, Patient, Cell biology, Evidence-based medicine, Therapy, Strategy, Mantle cell lymphoma