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The role of a second autologous stem cell transplant (ASCT) as salvage therapy is unclear, particularly with the availability of novel agents to treat progressive multiple myeloma (MM). We retrospectively reviewed all MM patients who received a second ASCT as salvage therapy at our center from March 1992 to December 2009. Eighty-one MM patients received a second ASCT for relapsed MM. The median time to relapse after first transplant was 39 months (9.83-100). All patients received reinduction therapy before the second ASCT. The high-dose regimen given before the second ASCT consisted of melphalan (MEL) alone in the majority. Complete response, very good partial response, and partial response were seen in 7.7%, 39.7%, and 50%, respectively, at day 100 post-ASCT; the median time to relapse after the second ASCT was 19 months. Early deaths occurred in 2.6%. Median progression-free survival (PFS) based on the time to myeloma relapse after first ASCT was 9.83 months (relapse ≤ 24 months) and 17.3 months (relapse ≥ 24 months) (P < .05). Median overall survival (OS) was 28.47 months (relapse ≤ 24 months) and 71.3 months (relapse >24 months) (P = .006). Second ASCT is a feasible and safe option for salvage therapy in MM. The best outcome was observed in patients whose time to progression was >24 months after first ASCT, as these patients had a subsequent PFS lasting over 1 year and an OS of almost 6 years., (Copyright © 2012. Published by Elsevier Inc.)

High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve excellent clinical responses in patients with POEMS syndrome (Jimenez Zepeda et al., Blood 2010;116:2403; Gertz et al., Am J Hematol 2005;79:319-328; Gherardi et al., Ann Neurol 1994;35:501-505; Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Salem et al., J Immunol 2009;182:2030-2040; Salem et al., Cancer Immunol Immunother 2010;59:341-353; Salem et al., Cell Immunol 2010;261:134-143). However, High-dose melphalan with ASCT should be considered carefully due to its treatment-related morbidity (Vuckovic et al., Blood 2003;101:2314-2317), especially in patients with poor performance status owing to polyneuropathy and multiorgan involvement, such as cardiac, respiratory, and renal failure. Significant increases in the concentration of circulating macrophage colony-stimulating factor, erythropoietin, IL-6, and TNF-α, reach near maximal values at approximately day +12, predating neutrophil engraftment, and clinically manifest with fever, rash and edema (Dispenzieri et al., Eur J Haematol 2008;80:397-406). Depending on the definition used, approximately 50% of patients satisfied criteria for engraftment syndrome (ES) (Vuckovic et al., Blood 2003;101:2314-2317). ES occurs in 27-47% of patients who undergo ASCT; mortality rate is reported from 8% to 18% (Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Vuckovic et al., Blood 2003;101:2314-2317). We have therefore reviewed our experience with ASCT in patients with POEMS syndrome who were treated with cyclophosphamide and prednisone as induction therapy followed by cyclophosphamide mobilization with an emphasis on treatment-related morbidity and frequency of ES. Our study confirms that ASCT is a feasible and efficacious treatment for patients with POEMS syndrome. In addition, the use of CP followed by cyclophosphamide mobilization decreases the incidence of PES leading to less morbidity and mortality rates., (2011 Wiley-Liss, Inc.)

Objectives: To understand the impact of therapy sequencing on progression‐free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low‐dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting. Methods: We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second‐line therapy, 575 patients were included. Results: Patients treated with LM had statistically similar 2nd PFS when re‐exposed to lenalidomide in second‐line therapy compared to those receiving non‐lenalidomide‐containing regimens (10.2 vs 14.0 months, P =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P =.004). Patients treated with LM also demonstrated deeper responses to second‐line therapy than their non‐LM counterparts. Conclusion: Our data suggest that patients progressing on LM who receive lenalidomide‐containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non‐lenalidomide‐containing second‐line regimens. Identification of patients mostly likely to benefit from further lenalidomide‐containing therapy is paramount. [ABSTRACT FROM AUTHOR]

Summary: Despite continuing improvements in the management of classical Hodgkin lymphoma (cHL), relapse remains associated with a risk of lymphoma‐related mortality. The biological composition of relapse tumour biopsies shows interpatient variability, which can be leveraged to design prognostic biomarkers. Here, we validated the RHL30 assay, a previously reported gene expression model in an independent cohort of 41 patients with relapsed cHL. Patients classified as high‐risk by the RHL30 assay had inferior failure‐free survival (FFS) after autologous stem cell transplantation (2‐year FFS 41% vs. 92%, P = 0·035). The RHL30 model is a robust biomarker that risk‐stratifies patients considered for autologous stem cell transplantation. [ABSTRACT FROM AUTHOR]

Post-autologous stem cell transplant (ASCT) studies have demonstrated that absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. To assess whether ALC recovery has prognostic significance in patients with multiple myeloma (MM) undergoing single ASCT, we conducted a retrospective analysis of ALC at different time-points in patients with MM. In total 769 consecutive patients who underwent single ASCT from January 2000 to December 2007 were evaluated. An ALC of ≥ 1400 cells/μL at day 0, day 15 and day 90 significantly correlated with a better overall survival (OS) (median OS of 111, 90.7 and 84 months vs. 74, 70.5 and 65 months, respectively,p< 0.001 for all time-points). Multivariate analysis showed that ALC is an independent prognostic factor for OS after ASCT. In conclusion, ALC is a surrogate marker of the host immune system that correlates with better survival in patients with MM undergoing single ASCT. Immunomodulatory drugs, vaccination strategies and cellular therapies in MM should be investigated. [ABSTRACT FROM PUBLISHER]

Autologous stem-cell transplant has been widely used to treat patients with AL amyloidosis. However, transplant-related mortality rates are high, and a recent randomized trial suggested that non-transplant regimens produced comparable results with less toxicity. In order to define the role of patient selection in stem cell transplantation, we evaluated 78 consecutive AL amyloidosis patients transplanted at our centre. Transplant-related mortality occurred in 11·5%. Complete haematological response and organ response were achieved in 56% and 60%. Median overall survival was significantly lower for patients with brain-type natriuretic peptide ( BNP) >300 pg/ml (17·5 months vs. not-reached) ( P = 0·0004), troponin-I >0·07 ng/ml (13·5 months vs. not-reached) ( P = 0·00001) and those not achieving a complete haematological response (88 months vs. not-reached) ( P = 0·0345); high BNP and troponin-I were the most important predictive factors in a multivariate analysis. Based on this study, patients with BNP <300 pg/ml and/or normal levels of troponin-I should be considered transplant candidates. [ABSTRACT FROM AUTHOR]

This is a randomized trial evaluating the safety and immunogenicity of one or two doses of 2009 pandemic H1N1 influenza vaccination in adults with lymphoid malignancies. Adults with a lymphoid malignancy receiving active systemic therapy, or within a year after autologous stem cell transplant, received one dose of AS03-adjuvanted A/California/7/2009 (H1N1) vaccine, and were randomized 21 days later to a second dose or no further vaccination. The primary outcomes were seroprotection and seroconversion rates by hemagglutination inhibition 21 and 42 days after initial vaccination. Twenty-two patients received one dose, and 20 patients received a second dose. Seroconversion rates at day 21 were 30% (one dose) and 5% (two doses), and subsequently 30% for both groups at day 42. Seroprotection rates at day 21 were 40% (one dose) and 15% (two doses), and subsequently 35% (one dose) and 40% (two doses) at day 42. Differences in serologic endpoints were not statistically significant between both study arms at day 42. Patients with low levels of B-cells (CD19-positive) had low seroconversion rates on days 21 (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.59-0.93, p = 0.043) and 42 (OR 0.12, 95% CI 0.01-1.07, p = 0.058). Only three of the 14 patients who received rituximab achieved seroprotective titers by day 42. Patients with lymphoid malignancies did not achieve rates of seroconversion or seroprotection seen in healthy subjects despite a second dose and the use of an adjuvant. Notwithstanding suboptimal immunogenicity, seasonal and pandemic influenza vaccination should continue to be recommended. [ABSTRACT FROM AUTHOR]

Summary The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi‐arm randomized phase II trial evaluating novel salvage therapies compared with R‐GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)‐eligible patients with relapsed/refractory diffuse large B‐cell lymphoma (RR‐DLBCL). This component of the LY.17 trial evaluated a dose‐intensive chemotherapy approach using a single cycle of inpatient R‐DICEP (rituximab, dose‐intensive cyclophosphamide, etoposide and cisplatin) to achieve both lymphoma response and stem cell mobilization, shortening time to ASCT. This report is the result of the protocol‐specified second interim analysis of the 67 patients who were randomized to either 1 cycle of R‐DICEP or to 3 cycles of R‐GDP. The overall response rate (ORR) was 65.6% for R‐DICEP and 48.6% for R‐GDP. The ASCT rate was 71.9% versus 54.3%, and 1‐year progression‐free survival rate was 42% versus 32%, respectively, for R‐DICEP versus R‐GDP. Although the improvement in ORR for R‐DICEP versus R‐GDP exceeded the pre‐specified 10% threshold to proceed to full accrual of 64 patients/arm, higher rates of grade 3–5 toxicities, and the need for hospitalization led to the decision to stop this arm of the study. CCTG LY.17 will continue to evaluate different salvage regimens that incorporate novel agents. [ABSTRACT FROM AUTHOR]