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The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (R/R cHL) after autologous stem cell transplantation (auto-SCT) is poor. Recently, the anti-CD30 monoclonal antibody-drug conjugate, brentuximab vedotin (BV), has shown remarkable activity in the setting of R/R cHL. In the pivotal phase II study, BV produced an overall response rate of 75% and a median progression-free survival of 6.7 months. Although these results have been reproduced by large registry studies, the impact of BV on the overall survival (OS) of patients with R/R cHL has not been addressed so far. The aim of this study was to examine the impact of BV on OS in the setting of post auto-SCT R/R cHL. Analysis was performed in a group of patients with R/R cHL after a previous auto-SCT reported in the Greek registry during the last 2 decades. By using a multivariate model and censoring patients at the time of subsequent allo-SCT or treatment with immune checkpoint inhibitors, we showed that treatment with BV in the posttransplant relapse setting has a positive impact on the outcome and results in significant improvement of OS. To our knowledge, this the first published study, addressing the impact of BV on the OS in the setting of posttransplant relapse. [ABSTRACT FROM AUTHOR]

International Staging System (ISS), serum free light chain ratio (sFLCR) and lactate dehydrogenase (LDH) are well known, easily assessed independent prognostic indicators of outcome in multiple myeloma (MM). The purpose of the study was to re-examine the prognostic contribution of these variables in a multicenter setting with special attention to MM patients treated with autologous stem cell transplantation (ASCT) or novel agents (NA). Three hundred and five symptomatic newly diagnosed MM patients were retrospectively studied. Twenty-seven per cent, 32% and 41% were in ISS stages 1, 2, and 3, respectively. Fifty-six per cent of them presented kappa light chain monoclonality; median sFLCR was 27.04 (0.37-1.9 × 105) and 47.97 (0.26-2.3 × 107) for kappa patients and lambda patients, respectively; patients with sFLCR above median constituted the high sFLCR group. Thirty-one per cent of patients had increased LDH. As first line treatment, 55.7% received conventional treatment and 44.3% NA. After induction, 24% underwent ASCT, whereas 76% received NA at any line, either bortezomib (82.5%), thalidomide (48%) or lenalidomide (27%). When the 305 patients were analyzed together, staging, high sFLCR and abnormal LDH were predictive of survival. The same was true for patients that never received NA, whereas neither high sFLCR nor abnormal LDH constituted adverse factors in patients that received NA frontline. In the last group of patients, no difference was observed between ISS stages 2 and 3. The median 5-year survival of patients that never received NA versus those who did frontline was 29% vs 47%, 7% vs 52% and 24% vs 40% in patients with abnormal LDH, high sFLCR and ISS stage 3, respectively ( p = 0.03, p < 0.00001 and p = 0.035). In conclusion, patients gaining the most from NA are those with an aggressive disease as reflected by advanced stage, abnormal LDH and high sFLCR. In addition, the adverse impact of these three variables is obscured by NA. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding the toxicity in patients with relapsed hairy cell leukemia who are treated with rituximab.

During the last decade several novel agents have been used in the management of patients with multiple myeloma. Immunomodulatory drugs and proteasome inhibitors exert their efficacy both directly by inducing apoptosis of myeloma cells and indirectly through the interruption of the interactions between myeloma and stromal cells in the bone marrow (BM) microenvironment. These interactions are crucial for myeloma cell growth and survival. The adherence of myeloma cells to BM stromal cells leads to the overproduction of several cytokines with angiogenic properties that enhance the survival and growth of myeloma cells through paracrine and autocrine loops. The correlation of these molecules with clinical features and survival of myeloma patients supports the importance of angiogenesis in the pathogenesis of the disease and reveals these cytokines as suitable targets for the development of novel anti-myeloma therapies. This review summarises all available preclinical and clinical data for the effect of novel agents that are used in myeloma therapy, such as thalidomide, lenalidomide, bortezomib and VEGF inhibitors, on angiogenesis, which is at least partially responsible for their remarkable anti-myeloma efficacy. [ABSTRACT FROM AUTHOR]

ATLL is etiologically associated with HTLV-I retrovirus. A population of 10 to 20 million worldwide is estimated to be infected by the virus, but only 1 - 4% develop ATLL during a 70-year lifespan. The latency period is more than 30 years. The aim of this study was to report two cases of ATLL in Greek patients with the concomitant study of their family members. A 55-year-old woman and a 59-year-old man presented with leucocytosis and lymphocytosis. Both were asymptomatic and physical examination was unremarkable except for minimal lymphadenopathy in the second patient. In both patients blood smears showed small-to-medium-sized, multilobulated lymphocytes, with different degrees of nuclear irregularity. Immunophenotypic study was as follows: CD2 + (97%), CD3 + (95%), CD5 + (95%), CD3/CD4 + (93%), CD3/CD25 + (84%), CD7 - /CD4 + (89%) CD2 + /HLA-DR + (53%), TCRaβ + (96%) and CD7-(7%). Bone marrow biopsy revealed a normal cellularity with dyserythropoiesis and scattered small lymphocytes (CD4 + on immunostaining) Serum HTLV I and II antibodies were positive. T-cell receptor γ-chain rearrangement was positive in blood lymphocytes by PCR. Cytogenetic analysis showed complex karyotypic abnormalities. DNA analysis by PCR demonstrated the integration of the HTLV-1 DNA in the DNA of the neoplastic T cells. Both patients rapidly developed acute type ATLL. In the first patient multiple subcutaneous nodules on the palmar surface of both hands were also observed. She received deoxycoformycin, which was stopped because of autoimmune hemolytic anemia. Corticosteroid treatment was initiated, with gradual improvement. She suffered from recurrent opportunistic infections. She is currently under interferon and zidovudine therapy with stable blood parameters. Chemotherapy was administered to the other patient with > 50% initial response. Both patients' families were tested for serum anti HTLV-I antibodies and their mates were found to be positive; they also had detectable viral DNA by PCR analysis while asymptomatic, with no abnormal clinical findings and normal white blood cell count and morphology. In conclusion, the two aforementioned patients are the first fully documented ATLL patients described in Greece. Investigation for HTLV-I antibodies should be mandatory in all patients with T-cell lymphoproliferative disorders. [ABSTRACT FROM AUTHOR]

We present the case of a 71 year-old man with secondary acute myeloblastic leukemia, who was successfully treated with low dose melphalan plus Epo plus G-CSF. We treated the patient with 2 mg of melphalan once a day orally, G-CSF 5 mg/kg 3 times a week and Epo 10.000 ui subcutaneously 3 times a week until the maximum response was obtained. Complete remission was achieved after 16 weeks of continuous treatment. Treatment-related toxicity was not significant. We recommend the use of low dose melphalan in elderly patients with high risk MDS as a treatment option. [ABSTRACT FROM AUTHOR]

CD55 and CD59 are complement regulatory proteins that are linked to the cell membrane via a glycosyl-phosphatidylinositol anchor. They are reduced mainly in paroxysmal nocturnal hemoglobinuria (PNH) and in other hematological disorders. However, there are very few reports in the literature concerning their expression in patients with acute leukemias (AL). We studied the CD55 and CD59 expression in 88 newly diagnosed patients with AL [65 with acute non-lymphoblastic leukemia (ANLL) and 23 with acute lymphoblastic leukemia (ALL)] using the sephacryl gel test, the Ham and sucrose lysis tests and we compared the results with patients' clinical data and disease course. Eight patients with PNH were also studied as controls. Red cell populations deficient in both CD55 and CD59 were detected in 23% of ANLL patients (especially of M 0 , M 2 and M 6 FAB subtypes), 13% of ALL and in all PNH patients. CD55-deficient erythrocytes were found in 6 ANLL patients while the expression of CD59 was decreased in only 3 patients with ANLL. No ALL patient had an isolated deficiency of these antigens. There was no correlation between the existence of CD55 and/or CD59 deficiency and the percentage of bone marrow infiltration, karyotype or response to treatment. However no patient with M 3 , M 5 , M 7 subtype of ANLL and mature B- or T-cell ALL showed a reduced expression of both antigens. The deficient populations showed no alteration after chemotherapy treatment or during disease course. This study provides evidence about the lower expression of CD55 and CD59 in some AL patients and the correlation with their clinical data. The possible mechanisms and the significance of this phenotype are discussed. [ABSTRACT FROM AUTHOR]

Aim: Bisphosphonates are potent inhibitors of osteoclastic activity and are used in the treatment of multiple myeloma (MM) in combination with chemotherapy. The effect of pamidronate on markers of bone resorption [cross‐linked N‐telopeptides of type I collagen (NTx)], markers of bone formation [serum alkaline phosphatase (BAP) and osteocalcin (OSC)], interleukin‐6 (IL‐6), β2‐microglobulin, CRP, paraprotein and disease‐related pain and skeletal events has been evaluated in 62 newly diagnosed patients with MM. Patients and methods: The patients were randomly assigned to two groups: the first included 32 patients under chemotherapy and pamidronate (group I) and the second 30 patients on chemotherapy only (group II). Pamidronate was administered at a monthly dose of 90 mg iv, and the above parameters were evaluated at the beginning of this study and after 1, 3, 6, 9, 12 and 14 months of treatment. Results: The addition of pamidronate to chemotherapy resulted in a significant reduction of NTx, IL‐6 and paraprotein from the 3rd month and of β2‐microglobulin, CRP and pain from the 6th month of treatment. No changes of NTx, IL‐6, β2‐microglobulin, CRP or skeletal events were observed in patients of group II, while paraprotein was significantly reduced after 6 months of treatment. The differences in NTx, IL‐6, paraprotein and β2‐microglobulin were statistically significant between the two groups. Multivariate analysis revealed a significant correlation between changes of NTx, changes of IL‐6 in both groups and reduction of pain and paraprotein in group I. Conclusions: These results suggest that pamidronate may have a synergistic action with chemotherapy in decreasing osteoclastic activity, in reducing markers of myeloma activity and myeloma related pain and in improving the quality of life in patients with MM. [ABSTRACT FROM AUTHOR]

Abstract: Tissue inhibitor of metalloproteinase-1 (TIMP-1) was evaluated in the pre-treatment serum of 55 newly diagnosed patients with symptomatic myeloma. TIMP-1 was elevated in 47% of patients and correlated with lytic bone disease and increased bone resorption. Importantly, TIMP-1 correlated with ISS stage (p =0.005) and was an independent prognostic covariate for survival [HR: 1.003 (1–1.006), p =0.004] in these patients who were all treated with novel agents (bortezomib and/or IMiDs) during their disease course. Our study provides evidence that pre-treatment serum TIMP-1 is associated with advanced myeloma and suggests the further evaluation of this molecule to better determine its prognostic potential in MM. [Copyright &y& Elsevier]

Purpose: To present our long-term experience regarding the use of chemotherapy plus low-dose involved-field radiotherapy (IFRT) for clinical Stage I-IIA Hodgkin''s lymphoma.Methods and materials: We analyzed the data of 368 patients. Of these, 66 received mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and 302 received doxorubicin (or epirubicin), bleomycin, vinblastine, and dacarbazine [A(E)BVD]. Patients with complete remission or very good partial remission were scheduled for low-dose IFRT (≤3200 cGy).Results: The 10-year failure-free survival (FFS) and overall survival (OS) rate was 85% and 86%, respectively. A(E)BVD-treated patients had superior 10-year FFS and OS rates compared with MOPP-treated patients (87% vs. 75%, p = 0.009; and 93% vs. 71%, p = 0.0004, respectively). Only 10 of 41 relapses had any infield (irradiated) component. Of the complete responders/very good partial responders treated with low-dose IFRT, those who received <2800 cGy had inferior FFS but similar OS as those who received 2800–3200 cGy. Adverse prognostic factors for FFS included age ≥45 years, leukocytosis ≥10 × 109/L, and extranodal extension. Secondary acute leukemia developed after MOPP with or without salvage therapy (n = 6) or after ABVD plus salvage therapy (n = 2). None of the nine secondary solid tumors developed within the RT fields.Conclusion: IFRT at a dose of 2800–3000 cGy is highly effective in clinical Stage I-IIA HL patients who achieved a complete response or very good partial response with A(E)BVD. The long-term toxicity with respect to secondary malignancies appears to be acceptable. [Copyright &y& Elsevier]