ALBERT

Description: Background Polycythemia vera (PV) is a subgroup of myeloproliferative neoplasm (MPN) BCL-ABL1 negative. The current therapy of PV should be aimed at preventing vascular complications and avoid increasing the risk of leukemic transformation. The therapy response monitoring is based in the European LeukemiaNet (ELN) unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera consensus process, published by Barbui T et al in Br J Haematol 2010;148(6):961-963. Objectives We conducted a study to assess in our clinical practice the aplicability of the standard criteria for resistance and intolerance proposed by ELN in patients (pts) with PV that have been treated with hydroxycarbamida (HU). Methods This is a retrospective study in a cohort of pts with PV enrolled in a single Hematology University center in South Brazil. All pts were treated according to PV guidelines, and the response monitoring was based on clinical practice. All database was compared to standard criteria proposed by ELN. Intolerance /resistance was defined by: a) need for phlebotomy to keep hematocrit 〈 45% after 3 months of at least 2 g/d of HU or b) uncontrolled myeloproliferation (ie, platelet count 〉 400 x109/L and white blood count (WBC) 〉 10 x109/L) after 3 months of at least 2g/d of HU or c) failure to reduce massive splenomegaly by 50% as measured by palpation or failure to completely relieve symptoms related to splenomegaly after 3 months of at least 2 g/d of HU or d) absolute neutrophil count 〈 1.0 x109/L or platelet count 〈 100 x109/L or hemoglobin 〈 10 g/dL at the lowest dose of HU required to achieve a complete or partial clinicohematologic response or e) presence of leg ulcers or other unacceptable HU related nonhematologic toxicities, such as mucocutaneous manifestations, GI symptoms, pneumonitis or fever at any dose of HU. Results We analyzed data from 33 patients with PV assisted in the last five years in our outpatient clinical data. The ELN criteria for resistance and intolerance were accessed in these patients. At diagnosis, 42,4% of pts were younger than 61yo, and 54,5 were male. Arterial hypertension, diabetes mellitus and dyslipidemia were identified on 21, 2 and 7 pts, respectively. Only one patient was tobacco smoker at diagnosis. Total of 5 pts showed WBC 〉 15 x109/L, and 7 pts showed platelets 〉 450 x109/L. Massive splenomegaly is a rare PV manifestation in our series, occurring in 2 pts. Five patients complained of symptoms related to PV as pruritus and vasomotor phenomena at diagnosis. Less than 5% of patients had been treated with 2 g of HU for more than 3 months. In daily practice, when the patient presented hematologic toxicity, the HU was decreased and, if the hematocrit was over 45%, an occasional phlebotomy was performed. In relation to platelets (less than 400 x 109/L) and leucocyte (less than 10 x109/L) counts, these targets were not used exclusively in the clinical practice to change treatment. The intolerance was easily discriminated in patients with leg ulcers and other non-hematological events. Conclusion These criteria were done based on an expertise consensus for international criteria standardization for clinical studies. Its application in a retrospective study, using clinical daily practice data is not adequate. The reason is that in the last years the main target to treat patients was the hematocrit above 45%, the exact number of platelets and leucocytes is still not a consensus to define resistance, so different counts had been used to guide treatment, we rarely used HU doses above 1500 mg/daily to treat our patients and massive splenomegaly was observed in very few patients. These criteria should be used most for prospective studies. Disclosures No relevant conflicts of interest to declare.

Description: Sustained deep molecular response (MR4.5) after imatinib treatment defines a subgroup of patients with chronic myeloid leukemia (CML) with better outcome and that probably would be able to stop treatment in the future, according to results of clinical TKI discontinuation trials. Most of these trials showed that patients with a long-term imatinib treatment and low Sokal risk have a higher probability of maintain a deep molecular remission after stopping treatment. OBJECTIVES The main objective is to review the molecular responses, overall survival and event free survival of CP CML patients that have been treated with imatinib in 14 hematology centers in South Brazil. Using our data basis we also would like to see how many of them present long-term imatinib treatment, sustained deep molecular remission and correlate these findings with the Sokal risk groups. These data would allow us to predict patient profile that could be able to discontinue the treatment in the future in a prospective clinical trial. PATIENTS AND METHODS This is a retrospective study in a cohort of pts with chronic myeloid leukemia chronic phase (CP) that have been treated in 14 hematology centers in South Brazil. All pts received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the ELN recommendations. MR(4.5) was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction. All tests were performed at a central standardized according to ELN. Event-free-survival (EFS) was measured from the start of imatinib to the date of any of the following events while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase. Overall survival (OS) was measured from the start of imatinib until death of any cause or to the date patient was last known to be alive. RESULTS Data from 474 patients was analyzed. After a median observation time of 46 months, 5-year overall survival (OS) was 86%, 5-year event-free-survival was 53%. Of the 474 patients, 258 had adequate PCR evaluations during treatment. 118 of 258 (45,7%) patients achieved MR(4.5) and 69 of 258 (27%) had sustained response for at least two years after a minimum time of treatment of 3 years. The cumulative incidence of MR(4.5) after 9 years was 76% (median, 3 years). In the group that achieved MR(4.5), there was only 1 (0,8%) death and 1 (1,1%) progression compared to 8 deaths (5,7%) and 8 progressions (7,5%) in the group without MR(4.5); these differences were significant with p=0,03 and 0,02 respectively. In the subgroup of 69 patients that had had been treated with imatinib for 3 year or more and sustained deep response (RM4,5) for at least two years, 21 pts had low Sokal risk, 7 pts intermediate Sokal risk and only 4 pts a high Sokal risk. Unfortunately, in 37 pts the Sokal risk could not be accessed due to missing information. CONCLUSION In our series MR(4.5) is reached in the majority of patients with long-term imatinib treatment. MR(4.5) is a predictor of outcome with only one disease progression and one death due to CML in this group of patients. Unfortunatly PCR are not available for all patients in our clinical practice, but this situation are improving. Regarding the 69 patients with TKI discontinuation trial criteria, we find out that 21 patients fulfill such criteria. In the future, according to the results of current stop trials it could be possible include this selected group of CP CML patients in a prospective clinical trial. Disclosures No relevant conflicts of interest to declare.

Description: Background Monitoring response to TKI therapy is one of the key management strategies of chronic myeloid leukemia (CML). Early molecular response to first-line TKI therapy is emerging as an effective prognostic factor indicator of long-term durable response and survival. Objectives We conducted a study to evaluate the importance of the early molecular response (EMR) at 3, 6 and 12 months (mo), and 3-year event free survival (EFS). Methods This is a retrospective study in a cohort of pts with chronic myeloid leukemia chronic phase (CP) enrolled in 14 Hematology centers in South Brazil. All pts received imatinib 400mg as first or second-line therapy. Patient evaluation and response criteria followed the ELN recommendations. EFS was measured from the start of imatinib to the date of any of the following events while on therapy: death from any cause, loss of complete hematologic response, loss of complete cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, or progression to accelerated phase or blastic phase. Results We analyzed data from 517 pts with CML-CP diagnosed since 1990. After a median observation time of 46 months, 5-year overall survival (OS) was 86% and 5-year event-free-survival was 53%. At 3 mo, EFS was 72,5% for 46 pts with BCR-ABLIS ≤10% compared to 58% for 14 pts with BCR-ABLIS 〉10% (p1% (p0,1% (p