The addition of cladribine to standard induction chemotherapy has no impact on the incidence and spectrum of infectious complications in newly diagnosed AML patients.

IntroductionImatinib mesylate (IM) remains the treatment of choice for chronic myeloid leukemia (CML) showing a remarkable efficacy and offers a perspective for long disease-free survival. Due to prolonged administration of IM, the questions about the possible impact on the development of secondary malignancies (SM) are raised.ObjectiveTo investigate the incidence and clinical outcome of secondary malignancies during IM therapy for CML.Material and MethodsThe records of 221 CML patients treated with IM between 2003–2013 in a single institution were reviewed. The Poisson regression model was used to estimate the relative risks for SM and death in CML patients.ResultsSecondary malignancies developed in eight out of the 221 patients (3.6%) receiving IM for a median of 61 months (range, 10–137 months). Female/male ratio was 5/3. Two patients were diagnosed with their CML at accelerated phase whereas 6 had chronic phase. The median age at IM initiation was 58 years (range, 31–72 years). Five of these 8 SM patients received IM after other treatments failure: interferon α (n=5), hydroxyurea (n=4) and cytarabine (n=1). Three patients received IM as a frontline therapy. All patients were on IM at 400mg daily at SM occurrence. The therapy for SM included surgery (n=3), chemotherapy only (n=3), and chemotherapy followed by radiotherapy (n=1). One patient did not receive treatment due to disseminated disease. All CML patients were in hematologic and complete cytogenetic response (CCR) at the time of SM development. All of them also met the criteria for major molecular response (BCR-ABLIS ≤0.1%). They continued their IM while receiving treatment for SM. Among eight patients with SM, five patients are alive and remain in CCR on IM whereas three patients died due to SM. The risks for SM development as well as death due to SM in CML patients were not statistically increased if compared to age-adjusted population.ConclusionsThe association between IM therapy for CML and SM development has not been found.

Extramedullary (EM) relapses of acute leukemia (AL) without concomitant bone marrow involvement are increasingly reported as a late complication after allogeneic hematopoietic stem cell transplantation (alloHSCT), however, the data regarding their incidence in larger cohorts of patients (pts), treatment options and long-term outcome are scarce. We retrospectively analysed this mode of leukemia recurrence in a group of 324 consecutive pts with AL (123 with ALL, 201 with AML, F/M 156/168, median age 29 years, range 10–61) who underwent alloHSCT in our institution between June 1993 and December 2007. 62 pts (34 with ALL, 28 with AML) relapsed (any site) after a median time of 8 months (range, 1–77 ). 7 (11,3 %) out of all pts who relapsed (2 with pre-pre B ALL, 2 with CD10+, Ph+ ALL, 2 with 45 X, −Y, t(8;21) AML, 1 with CD117+, 46, XY, t(19;11), del 13 AML, F/M 4/3, median age 29 years, range 28–40 years) developed isolated EM infiltrates after a median time of 13 months (range, 8–33 months) after alloHSCT. The leukemic origin of pathologic infiltrates was confirmed in each case by immunohistochemical methods or flow cytometry with the use of appropriate combination of the following markers: CD10, CD19, CD20, CD45, CD79a, CD34, TdT, CD13, CD33, CD117, MPO, lysozyme. We revealed complete donor chimerism in 6/7studied pts. 4 pts (3 with ALL, 1 with AML) developed skin and/or subcutaneous tissue infiltrates; in one of them ( patient with pre-preB ALL) leukemic tumor of the peritibial soft tissues was additionally observed. Other sites of EM relapse included (No. of cases/diagnosis): leptomeninges of the brain (1/Ph+ ALL), paraspinal soft tissues (1/AML), small intestine and the root of mesentery (1/AML). Treatment plans for those isolated EM relapses included (No. of cases/diagnosis): 1/involved-field radiotherapy (IF-RT) followed by chemotherapy (CHT) and interpheron-alpha (2/pre-pre B ALL), 2/imatinib + CHT + steroids and methotrexate intrathecally (1/Ph+ ALL), 3/imatinib + CHT (1/Ph+ ALL), 4/CHT (1/AML), 5/dasatinib (1/CD117+ AML,), 6/surgery (1/AML). In one patient who showed peritibial infiltrates, donor lymphocyte infusions and daunorubicine injections to the femoral artery, as well as total skin electron irradiation due to recurrent skin involvement were additionally applied. Unfortunately, all of the patients died after a median time of 10 months (range, 1–30) due to resistant systemic relapse and/or infectious complications. Only one patient who responded well to IF-RT was alive more than 2 years following relapse. Our data indicate that the graft-versus-leukemia effect observed in the EM sites of the body may not be as effective as in the bone marrow in some pts with AL following alloHSCT. Isolated EM disease affects slightly more often ALL than AML pts relapsing after alloHSCT. Sites of EM relapses vary widely among the pts with skin and/or subcutaneous tissue being frequently involved. Local radiation therapy seems to be effective treatment option, but it does not prevent from systemic relapse and should be followed by other therapeutic modalities. In selected pts with specific indications individualized management, such as intraarterially administered anthracyclines or total skin electron irradiation may result in transient improvement. Tyrosine kinase inhibitors such as imatinib or dasatinib should also be considered in cases of Ph+ ALL or c-kit positive AML. According to our experience occurrence of EM relapse following alloHSCT is associated with poor prognosis and the optimal therapy remains a challenge.

1011 Poster Board I-33 Background: Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation increases the risk of infectious complications. Material and methods: 118 AML patients, included in two consecutive randomized trials between 1999-2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65 ). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/- purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively. Results: The frequency of neutropenic fever as well as microbiologically documented bacterial, fungal and viral infections during induction and consolidation did not differ between two compared groups - receiving or not purine analogues. Time to infection occurrence and infection duration were similar in both study groups. During induction and both consolidation treatments significant lower values of lymphocytosis were observed in the group of patients treated with purine analogues. There was a slight tendency to increased rate of mucositis for patients treated with purine analogues (60% vs. 44.3%, p=0.07) during induction treatment, while infections affecting skin and soft tissues were significant frequent for patients treated without purine analogues (43.3% vs. 18%, p=0.03) during second consolidation treatment (high dose AraC). The usage of intravenous anti-infectious medications (antibiotics, antifungal, antiviral) and periods of hospitalization did not differ between two groups in this study. Conclusions: We conclude that the use of purine analogues, either cladribine or fludarabine along with conventional induction and consolidation therapy does not aggreviate infectious complications in adults with AML. Disclosures: No relevant conflicts of interest to declare.

4358 Background Addition of purine analogues to standard induction therapy of acute myeloid leukemia (AML) had previously been demonstrated to increase complete remission rate and does not aggravate infectious complications. The aim of this study was to analyze whether the use of cladribine or fludarabine during induction and consolidation treatment increase the need for more frequent transfusions of red blood cell concentrates, platelet concentrates and fresh frozen plasma. Material and methods 118 AML patients, included in two consecutive randomized trials between 1999–2006 in a single centre were analyzed. Induction therapy consisted of daunorubicin + cytarabine (DA-7, n=53) alone or in combination with cladribine or fludarabine (DAC-7 + DAF-7, n=65). Consolidation included one course of high-dose AraC + mitoxantrone and one course of high-dose AraC +/− purine analogues. A median age was 45(17-58) years and 48(20-60) years for patients treated with and without purine analogues, respectively. Results During induction treatment 7 (1-19) units of red blood cell concentrates (median and range) was transfused in the group with purine analogues compared to 6 (1-23) in the group without purine analogues, p=0,24. Number of transfused platelet concentrates bags was 6 (1-30) in the group of purine analogues and 7 (0-19) in the group without purine analogues, p = 0.49. In the group with purine analogues 0 (0-31) units of fresh frozen plasma was transfused compared to 0 (0-26) in the group without purine analogues, p = 0.91. During HAM consolidation therapy 3 (0-11) units of red blood cell concentrates was transfused in the group with purine analogues compared to 2 (0-9) in the group without purine analogues, p = 0.15. Number of transfused platelet concentrates bags in the group with purine analogues was 2 (0-8) vs. 2 (0-12) in the group without purine analogues, p = 0.25. In the course of HAM consolidation treatment - 0 (0-56) units of fresh frozen plasma was transfused in the group with purine analogues compared to 0 (0-0) in the group without purine analogues, p = 0.027. During HD Ara-C consolidation therapy 3 (0-7) units of red blood cell concentrates was transfused in the group with purine analogues compared to 2 (0-5) in the group without purine analogues, p = 0.03. Number of transfused platelet concentrates bags in the group treated with purine analogues was 3 (1-12) vs. 3 (1-6) in the group without purine analogues, p = 0.61. In the course of HD Ara-C consolidation treatment 0 (0-9) units of fresh frozen plasma was transfused in the group with purine analogues compared to 0 (0-11) in the group without purine analogues, p=0,34. Conclusions The vast majority of the obtained results did not reveal any significant differences between the group of AML patients treated with or without purine analogues. During HAM consolidation treatment statistical significance for more fresh frozen plasma units transfused was shown in the patients treated with purine analogues, although the median value was the same in both groups (0). This situation was random and independent of prior use of purine analogues in the induction therapy, because in one of the woman-patient gynecological complications and DIC occurred (bleeding from uterine fibroids). This situation required intensive supportive therapy including fresh frozen plasma transfusions. In one case 56 units of fresh frozen plasma was transfused and in second arm of the study was not applied a plasma transfusions in any patient. Also during second (HD Ara-C) consolidation treatment number of transfused units of RBC's concentrates was significant higher in the group of patients treated with purine analogues, although the median values were similar (3 vs 2). These differences may arise from the fact that in some patients - especially in group of patients treated with purine analogues who obtained the better results of therapy – second HD Ara-C treatment was also more often followed by mobilization and collection of stem cells from peripheral blood for transplantation. In the procedure of stem cells collection a higher hematocrit value is recommended – so frequent decision for RBC's transfusions was made in this group of patients. We conclude that the use of purine analogues in the treatment of AML patients does not increase the need for more frequent transfusions of red blood cell concentrates, platelet concentrates and fresh frozen plasma. Disclosures: No relevant conflicts of interest to declare.