Background: Background: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by the presence of driver mutations (JAK2, CALR or MPL) in most of the patients. The development of next generation sequencing (NGS) has favored the incorporation of mutational information in novel prognostic scores. However, most of these risk stratification models also include cytogenetic information, which is only available for a fraction of patients with this disease, thus reducing their real-life applicability. Mutation-enhanced international prognostic scoring system for transplant-age patients (MIPSS70) is based on clinical and mutational risk factors and it is useful in the absence of cytogenetic information, but it has not been validated yet in a real-life clinical setting. Aims: Aims: To validate MIPSS70 risk stratification model for transplant-age PMF patients from a multicenter database. Methods: Methods: From the GEMFIN multicenter database, 668 myelofibrosis patients with enough information to calculate MIPSS70 were selected. As the score is intended for patients aged ≤70 years with PMF, the final analysis was carried out in 218 patients meeting these criteria. Patients who received allogeneic stem cell transplantation were censored on the date of transplantation.

Background:Currently one of the most burning issues regarding the specific treatment of Chronic Myeloid Leukemia (CML) with Interleukin‐2‐inducible T‐cell kinases (ITKs) is whether in a percentage of patients who meet specific requirements treatment interruption could be attempted and maintain molecular relapse‐free survival without treatment restarting with the consequent reduction of side effects related to medication and the progressive increase in the quality of life of patients.Aims:To analyse molecular relapse‐free survival after suspension of Imatinib, Nilotinib or Dasatinib, which achieved and maintained a Molecular Response ≥ 4.5 log for at least 36 months.Methods:Multicenter prospective observational post‐authorization follow‐up study of patients with Chronic Phase Ph+ CML (CP‐CML). Inclusion criteria: minimum ITK treatment time of 5 years, no resistance to a previous ITK, no accelerated phase diagnosis or blast crisis and those who have achieved and maintained the Molecular Response ≥ 4.5 log for at least 36 months prior to treatment interruption. These patients were candidates for discontinuation of ITKs. Molecular monitoring of bcr‐abl oncogene levels was performed using the Real‐Time Reverse Polymerase Chain (RT‐PCR) technique with the GeneXpert automated system with a sensitivity of 5 log.Results:71 patients with CP‐CML were discontinued. 51 discontinued Imatinib treatment, 7 discontinued dasatinib treatment and 12 discontinued Nilotinib treatment. The preliminary rates of Molecular Relapse Free Survival (MRFS) and Treatment Free Remission (TFR) are consistent with those obtained in the different clinical trials, and no progression to advanced stages of the disease has been reported. With a median follow‐up of 9 months, 78% remain without specific treatment with ITK for not having lost the major molecular response, (BCR ABL ≤ 0.1%) cut‐off point established in the study as a criterion for reintroduction of ITK treatment. Relapse occurred before 6 months of discontinued treatment with a median of 3 months.Summary/Conclusion:Discontinuation of treatment with ITKs translates into clinical benefit for patients with CP‐CML, as it would reduce treatment‐related side effects and improve quality of life.

The term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. The term is controlversial for some authors and the optimal treatment is not well established. Therapy should be based in the control of clonal plasma cell disorder. There is few clinical reports regarding evolution of MGRS with novel drugs for GM. We present a clinical case of severe MGRS with a rapid hematological and renal response to Bortezomib (Bz) treatment with complet recovery of kydney function.

In the latest recommendations for the management of chronic‐phase chronic myeloid leukemia suboptimal responses have been reclassified as “warning responses.” In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first‐line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty‐six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression‐free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months ( P = 0.002); as well as the probability of achieving a deep molecular responses (MR 4.5 ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively ( P = <0.001) .The treatment change to 2GTKI remained safe; however, we have observed a 19% of treatment discontinuation due to side effects. We have observed an improvement of molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival. Am. J. Hematol. 89:E206–E211, 2014. © 2014 Wiley Periodicals, Inc.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1–8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3–18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1–54.2). Median overall survival (OS) was 30 months (95 % CI 25.6–34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.

Abstract Abstract 4942 INTRODUCTION. Patients with Mantle cell lymphoma (MCL) have an adverse outcome after relapse due to chemorefractory disease with conventional treatments. Bendamustine, a nitrogen mustard compound chemically related to the alkylating agents, has demonstrated high efficacy with a low toxicity profile in reported clinical trials. AIM. To analyze the Spanish experience in patients with relapsed/refractory MCL treated with Bendamustine. METHODS. Retrospective analysis of spanish experience in relapsed/refractory MCL treated with Bendamustine alone or in combination. This study has been approved by local ethical committees. RESULTS. Currently, there are 36 patients registered and 28 are available for this analysis. Patients'characteristics: 69% male, median age 65 years old (range 41–81), 87% ECOG≤ 1, 83% Ann Arbor stage IV, 37% high risk MIPI and 9% blastic variant. Previous regimens were CHOP or CHOP like ± R in 42.5%, HyperCVAD/MtxAraC ± R in 42.5%, R-CVP in 9% and other regimens in 6%. Median number of previous treatments were 2.6 (range 1–6), all patients had received prior Rituximab and 73% had chemosensitive disease to the last treatment. Bendamustine regimen was R-B (R-375mg/m2 D1, B-90 mg/m2 D1-2) in 78% patients, R-B with B-70 mg/m2 in 8%, B alone in 3%, R-B-Bortezomib in 3% and R-B plus consolidation (SCT, Y90Ibritumomab-tiuxetan) in 8%. Median number of cycles was 4.61 (range 1–7). G- CSF support was administered in 43% of cycles. Response: Overall response rate was 73%, with 43% CR & uCR and 30% PR. Survival: Median overall survival from diagnosis is 8,26 years (range: 1.6–11,6 years) without plateau. Median progression free survival (PFS) after Bendamustine treatment was 16 months (95% CI: 11.7–20.4), data that compares favourably with patients' PFS to previous therapy (12 months, 95% CI: 6.5–17.5). Median PFS for patients who achieved CR/uCR is 32.6 months (95% CI: 19.9–45.4) versus 11 months in patients with PR (95% CI: 3.9–18.8). With a median follow-up for surviving patients of 12 months since Bendamustine treatment, the estimated OS at 3 years is 47% (+ SD 14%). Toxicity: No treatment related mortality has been described so far. Over 152 cycles, only 10 hospitalizations due to febrile neutropenia were reported. No one case of lysis tumoral syndrome has been reported. CONCLUSION. Bendamustine plus Rituximab is a good rescue treatment in non selected pretreated patients with mantle cell lymphoma. CR rate and duration of response seem to reproduce in current clinical practice the good data reported in previous clinical trials and compares favourably with other available treatments. Disclosures: No relevant conflicts of interest to declare.