Chronic Myeloproliferative Syndrome Research Articles

Esplenectomía por tumor hematopoyético extramedular esclerosante del bazo

Extramedullary hematopoietic tumors are rare and characterized by the presence of hematopoietic elements at various stages of maturity, atypical megakaryocytes, and fibroblastic proliferation. We report the case of a patient with sclerosing extramedullary hematopoietic tumor of the spleen.The patient was 71-year-old man with a history of hypertension, diabetes, and hepatitis C virus infection. Multiple spleen lesions were identified in imaging tests during workup due to abdominal discomfort. Although a vascular tumor was suspected, laparoscopic splenectomy was decided after considering other possible causes. The pathology examination revealed a sclerosing extramedullary hematopoietic tumor of the spleen, which was confirmed by immunohistochemical tests. These tumors are usually single or, less frequently, multiple lesions affecting different organs and are associated with chronic myeloproliferative syndromes. The histologic confirmation is mandatory due to their similarity to malignant tumors. Extramedullary hematopoietic tumors are rare, and there is little scientific clinical evidence regarding their diagnosis and management. The histological confirmation is mandatory due to their similarity to malignant tumors.

Secondary Acute Myeloid Leukemia from a Previous Chronic Myeloproliferative Neoplasm: A Study of Grelam-Chile Concerning Chilean Patients on Behalf of AML Pethema Registry

Introduction: Secondary Acute Myeloid Leukemia (sAML) from Chronic Myeloproliferative Neoplasm (chMPN) is associated with an unfavorable prognosis and is characterized by a unique set of cytogenetic and molecular features distinct from de novo AML. The only cure for these patients is allogeneic Stem Cell Transplantation (SCT), which usually is not possible given the advanced age and comorbidities from this patient population. Methods: We present a retrospective analysis of sAML Chilean patients due to chMPN from the multicentric epidemiological registry of AML of the PETHEMA Spanish Group. Results: There are 802 AML Chilean patients incorporated in the online PETHEMA platform. 158 are sAMLand 26 are secondary to chMPN. Compared with the sAML group, patients with previous chMPN were mainly male (56% vs. 76%, respectively), had a larger white blood cell count (32,720 mm3 vs. 61,130 mm3), and had splenomegaly (P <0.05). There was no difference in age (median 62,35 years old), peripheral blood blasts (media 28,8%), fibrinogen (287 mg/dl), or other laboratory tests (p>0.05). Regardless of the type of chMPN: Chronic Myeloid Leukemia: 8 patients: Chronic myelomonocytic leukemia: 5, Primary Myelofibrosis: 5, Chronic Myeloproliferative Syndrome not specified subtype: 6, Polycythemia Vera/essential Thrombocytosis 2. 50% received previously chemotherapy, mainly Tyrosine Kinase Inhibitors (7) and hydroxycarbamide (7). Regardless sAML % had an abnormal karyotype. Treatment used, it was Anthracycline/Daunorubicin (38%), azacytidine with or without Venetoclax (19%), and palliative care (23%). In the first induction, the rate of Complete response (CR), or complete response with incomplete hematological response (iCR), was reached in only 3 patients, and these had negative MRD. From the patients with partial responses, 9 patients received a second line of treatment, mainly azacytidine. After that, three more patients reached CR. Only one patient received allogeneic SCT. The average stay in the hospital was 41,4 days, and Overall survival (OS) was 12,2 months (OS in all sAML was 14,2 months, N.S. p>0.05). The mortality rate was 84%, and the main cause was progressive disease in 60% of those cases. Conclusion: We present our local experience with this type of sAML. The outcome remains poor; it seems that allogeneic SCT is the only cure, but most patients cannot reach it. More research is needed to improve the high rates of mortality for this patient population.

P392 POST–THROMBOEMBOLIC PULMONARY HYPERTENSION: A COMPLEX CASE

Abstract Introduction Patients with post–thromboembolic pulmonary hypertension (CTEPH) achieve functional recovery after pulmonary endarterectomy (PEA). 40% of them are inoperable (1,2). Clinical case 66–year–old man admitted in 2012 to our ward for dyspnea on exertion and high echocardiographic probability of pulmonary hypertension (PI). Medical history: smoking; thalassemia trait; COPD; splenectomy at 13; diagnosis of chronic myeloproliferative syndrome. BP: 120/70 mmHg. NYHA class III. Blood tests: Hb: 9.4 g/dl; MCV: 70; HCT: 30%; PLT: 511; WBC: 14.84 (Mo 13%).NT–pro BNP:933. Autoantibodies and tests –HIV: negative. EGA in AAPaO2: 53 mmHg, PaCO2: 32 mmHg, SO2: 87%. PFR: FEV1: 68% FVC:74%, FEV1/FVC:72.DLCO:75%.6MWT:450m,Borg:0/3;Baseline SO2: 86%,final SO2 74%. On ECG: sinus r. at 64 beats/min. Echocardiogram: left sections within limits; right ventricle:DTD:30mm; RV/LV< 1; right atrial area: 19cm2, PAPs: 70+5 mmHg (Vel: 4.1 m/s), AcT: 90 msec. TAPSE: 16mm. Performs pulmonary CT scan with contrast medium: negative for pulmonary embolism; some 1 cm bubbles of emphysema in the subpleural area of the right middle lobe; right heart catheterization: PAD: 13mm; PAPM: 50mm; IC: 4.1l /min/m2; RVPtot:11WU;RVP:art:5.2WU;WP:11mmHg.Haematological diagnosis of thalassemia intermedia and exclusion of myeloproliferative syndrome/P lung scintigraphy is positive for multiple bilateral perfusion defects. The possibility of PEA for peripheral lesions at the referral Centre, therapy with warfarin (TAO), riociguat and bronchodilators was started., discontinued therapy with TAO. Finding of recurrence of pulmonary micro embolism on scintigraphy. At the end of the intravitreal treatments with resumption of TAO, at control catheterization evidence of PAD:5mm PAPm19mmHg;WP:9mmHg;IC: 3.4l/min/m2; RVPart:2.9 WU;NYHA:II. Discussion Not all CTEPH from thalassemia intermedia can perform PEA (3). Hypercoagulability is an important pathogenetic mechanism in the genesis of PH (4) and comorbidities have a significant role in the prognosis and response to medical therapy. COPD is the comorbidity that favors hypercoagulability, worsens pulmonary ventilation and gaseous exchanges (5). Conclusions In thalassemia intermedia with inoperable CTEPH, hypercoagulability is the condition that most influences the prognosis and efficacy of vasodilator therapy.

Prévalence des Effets Indésirables des Inhibiteurs de Tyrosine Kinase Utilisés dans le Traitement de la Leucémie Myéloïde Chronique au CHU de Sidi Bel-Abbès

Chronic myeloid leukemia (CML) is a malignant hemopathy within the framework of chronic myeloproliferative syndromes, predominant on the granular line. Her drug treatment is based on tyrosine kinase inhibitors (TKIs) which inhibit the abnormal BCR-ABL protein kinase that causes CML and thus block the signals that cause cancer cells to multiply abnormally. However, other proteins are also inhibited, so they can cause a wide range of adverse effects (AEs). The objective of this study was to study the prevalence of AEs of TKIs used in the therapeutic management of CML by the hematology department of University Hospital Center (UHC) of Sidi Bel-Abbes in Algeria and that of the ITK discontinuation following an AE. It was a retrospective descriptive study carried out over a period of four months, from April 01st, 2021 to July 31st, 2021, on CML patients treated with TKI in the hematology department of Sidi Bel-Abbes HUC in Algeria. The primary outcome measure was the prevalence of AEs associated with the use of normal dosages or overdose of the following TKIs: Imatinib, Dasatinib and Nilotinib. Data were collected from patient charts, filled by doctors of hematology department, using questionnaire, and analyzed by Statistical Package for the Social Sciences software, version 20. A total of 40 patients were included, including 22 women, mean age 51.55±11.66years (23-78). Twenty-six patients reported at least one AE. Among the 106 AEs declared, 69 AEs (65.09 %) declared with Imatinib, 26 AEs (24.53 %) with Dasatinib and 11 AEs (10.38 %) with Nilotinib. A predominance of musculoskeletal effects 43 (40.56 %), followed by general disorders 18 (17 %), myelosuppression 14 (13.20 %) and digestive system 12 (11.32 %). AEs were responsible for permanent discontinuation of ITK in three cases (11.54 %), including two cases (07.70 %) on Imatinib because of neutropenia and one case (03.84 %) onDasatinibsuffering from pleural effusion. AEs could be controlled in 13 (50 %) of cases, including 9 (34.62%) by temporary discontinuation and 4 (15.38 %) by reducing the dosage, allowing improvement of symptoms and continuation or reintroduction of treatment. The prevalence of AEs was high in the studied population, their occurrence was inevitable, good management of AEs from the start of treatment is necessary to avoid switching to another TKI, especially in good responders. It is recommended to establish a low-sodium diet beforehand for all TKIs and a low-carbohydrate diet, especially for Nilotinib, and not to rush to stop the TKI because most often, EIs regress over time in order to allow good therapeutic adherence and obtain better results.

T(10;12)(q24;q15): A new cytogenetic marker in hematological malignancies

Cytogenetic studies have played a crucial role in the discovery of genes involved in several diseases. In the field of oncohematology, cytogenetics is still necessary for the classification and prognosis of many diseases. Here we report a new recurrent chromosome translocation, t(10;12)(q24;q15), in two patients with different hematological malignancies: myelodysplastic syndrome with excess blasts (MDS-EB), and myelofibrosis (MF) secondary to essential thrombocythemia (ET). The chromosome alteration was observed as a sole karyotype change in the patient with MDS-EB, both at the initial diagnosis and following progression to MDS-EB2. A putative HMGA2-KLLN rearrangement by RNA-sequencing was detected in this patient. The patient with ET, had a normal karyotype at diagnosis and the t(10;12)(q24;q15) translocation emerged as a sole cytogenetic alteration after transformation, and when MF was evident. We reviewed the literature to determine whether this chromosome abnormality had previously been described in other hematological patients and found two cases: an aggressive T-cell lymphoblastic lymphoma (T-LBL) and a case of transformed chronic myeloproliferative syndrome (CMS), in both of which t(10;12)(q24;q15) was also the only karyotype change. The clinical evolution of all four cases suggested that t(10;12)(q24;q15) is associated with a poor outcome in oncohematological patients.

Trombocitemia esencial en pediatría: caso clínico

Chronic myeloproliferative syndromes are rare disorders in pediatric age, for which the knowledge of the pathology and its management is limited. Chronic myeloproliferative syndromes in adults are commonly driven by JAK2 and MPL mutations, but in pediatrics there is no clear relationship. Currently, there are guidelines and protocols for the management of adult patients, which allows risk stratification and recommended treatment. However, this would not be the case in pediatric patients. We present a patient with essential thrombocythemia and the differential diagnoses that were studied at the Alejandro A. Posadas hospital.

Morbidity and Mortality Associated with Performing Bone Marrow Aspiration and Biopsy

Background: Bone marrow aspiration and biopsy are diagnostic methods in the study of hematological diseases. Complications are rare. Knowing the morbidity and mortality related to the procedure is essential in order to implement preventive behaviors and improvement plans. Objective: To determine the incidence of complications in patients over 18 years who were undergone to bone marrow biopsy and aspiration in a university hospital between October 2013 and May of 2015. Furthermore, frequency, socio-demographic and clinical characteristics were established as well. Materials & methods: Observational, descriptive and retrospective study. The unit of analysis was biopsies and bone marrow aspirations. The information was obtained from the database of outpatient hematology ward, into the program Group of Education and Monitoring of Egress (GESE) of the Hematology Service of Hospital de San Jose (Bogota, Colombia), and from medical records. Results: A total of 1252 bone marrow aspirates and biopsies were performed on 914 patients. Seventy-seven complications were reported, which corresponds to 6.15% of all documented procedures. The most frequent complication was: pain (100%), being more affected the women (66%), OR 1,91(IC 1,18-3,11) p=0,003. Regard to pathology diagnosis, 53.2% of biopsies were histologically normal hematopoiesis, followed by 16.8% for chronic myeloproliferative syndromes, which was the diagnosis most commonly associated with bleeding events (40%):OR 8,9 (IC 1,2-66,44) p=0,006, and death (1.3%). Conclusion: Pain was the most frequently reported complication, and among bleeding complications, chronic myeloproliferative disorders were the most common diagnosis. The largest number of complications in women may be related to the anatomical differences between the genders. It is recommended to improve post-procedure analgesia and prospective studies to establish association between complications and diagnosis.

Disease and Therapy Associated Complications of the Central Nervous System after Allogeneic Hematopoietic Cell Transplantation - a Significant Proportion of Patients Will Suffer from Permanent Damage

Introduction: Neurological symptoms after allogeneic hematopoietic cell transplantation (HCT) represent diagnostic challenges, since their onset can be rapid and permanent neurological damage is imminent. Little data is available on incidence, morbidity and mortality of central nervous system (CNS) complications after allogeneic HCT.Methods: We retrospectively analyzed data from 1204 patients undergoing allogeneic HCT at our center within the last 10 years. Out of this cohort, 102 patients (8.6%; 38 women and 64 men, median age 55 years, range 19-75 years) suffered from 107 post-HCT CNS complications. Underlying diagnoses were acute (ALL n=24; AML n=49) or chronic leukemia (CLL n=2; CML n=1; CMML n=2), myelodysplastic (n=8) or myeloproliferative (n=5) syndromes, non-Hodgkin lymphoma (n=10) or severe aplastic anemia (n=1). Conditioning was performed using reduced-intensity (n=61) or myeloablative (n=41) regimens. Grafts were applied from matched related (n=22), mismatched related (n=1), haploidentical (n=4), matched unrelated (n=49) or mismatched unrelated donors (n=26). 41 patients in the cohort suffered from acute (median grade 1; grades 1-4) and 41 patients from chronic GvHD (limited n=20; extensive n=21), respectively.Results: CNS complications comprised cerebrovascular events (hemorrhagic, n=26; thromboembolic, n=10), infections (n=19; viral infections including CMV and VZV n=11; bacterial n=2; toxoplasmosis n=6), toxic leukoencephalopathy (n=11), inflammatory changes without detection of underlying cause (n=14) including cerebral vasculitis or cerebral graft versus host disease (GvHD), disease relapse (n=13; meningeosis leucaemica n=10; myeloid sarcoma of the dura n=1), secondary intracerebral tumors (n=2), posterior reversible encephalopathy syndrome (PRES; n=4), seizures (n=6), migraine (n=1), or neurological and psychiatric syndromes without detection of a defined etiology (n=2). Median time between HCT and onset of CNS symptoms was 4.6 months (range, 0-155 months). CNS complications occurring early after HCT comprised hemorrhagic events (median 1.4 months after HCT; 0.2-107.9 months), seizures (median 3.0 months after HCT; 0.1-6.9 months), infections (median 4.7 months after HCT; 0.1-70.3 months), leukoencephalopathy (median 3.7 months; 0-33.6 months) and psychiatric disorders (median 1.3 months; 0.8-6.4 months). Other complications occurred later (p=0.006) comprising inflammatory disorders without a definite cause (median 7.1 months; 1.2-97.4 months), ischemia (median 29.9 months; 0.6-95.5 months), and malignant causes (median 10 months; 1.7-156 months).Treatment was guided by the respective diagnosis and symptoms including transfusion of platelet concentrates, interventional recanalization, antibiotics or virostatic drugs, immunosuppression, or systemic and/or intrathecal chemotherapy. These therapies led to complete resolution of neurological symptoms in 31 (30%) patients. In 43 patients (42%) amelioration with residual symptoms (n=15; 15%) or stabilization (n=28; 27%) was achieved. In 28 cases (27%) no response to therapy was observed resulting in a letal outcome (causes of death: cerebrovascular events n=7 (19%); infections n=10 (53%); leukencephalopathy n=2 (18% ); GvHD n=1 (7% l); CNS malignancy n=6 (40% ); unknown cause n=2).Risk factors for the development of CNS complications were thrombocytopenia (bleeding, n=18), positivity for toxoplasmosis before HCT (toxoplasma infections, n=6), arterial hypertension (PRES, n=4) and possibly irradiation of the neurocranium (inflammatory diseases; n=4).Median overall survival was 13.8 and 6.4 months after HCT and onset of CNS complications, respectively. Cumulative incidence of CNS disease related deaths was 11% and 21% at 100 days and 12 months, respectively (1% and 2% for the complete patient cohort of 1,204 patients).Conclusions: Complications and/or manifestations in the CNS account for a significant number of HCT-related complications resulting in significant mortality and morbidity. 70% of these patients will suffer from irreversible neurological damage. Therefore, precise and timely diagnosis is necessary to guide causal therapy and prevent permanent damage. DisclosuresNo relevant conflicts of interest to declare.

Abstract P1-10-03: Biosimilar filgrastim in the treatment of patients with breast cancer undergoing neutropenia-inducing chemotherapy: A subanalysis of the NEXT study

Abstract Introduction Febrile neutropenia (FN) is a frequent and serious complication in breast cancer patients undergoing chemotherapy. In addition to being a major risk factor for infection-related morbidity/mortality and disease progression, FN can lead to dose delays and reduction. Nivestim™ (Hospira Inc), a biosimilar filgrastim, is a granulocyte colony-stimulating factor licensed for the treatment of neutropenia and FN induced by myelosuppressive chemotherapy. The NEXT (Nivestim safety profile in patiEnts treated with cytotoXic CT in real-life clinical pracTice) study was a prospective real-world trial assessing the safety of curative or prophylactic biosimilar filgrastim in the treatment of patients undergoing chemotherapy. The large size of this study enabled a subanalysis to be performed in breast cancer patients; the results are presented herein. Methods NEXT was a prospective, noninterventional, longitudinal, multicenter French study (NCT01574235). Patients with a solid tumor or a malignant hemopathy (excepting chronic myeloproliferative and myelodysplastic syndromes) undergoing or starting neutropenia-inducing chemotherapy were enrolled. Objectives were to evaluate safety and incidence of FN and infection. Patients received biosimilar filgrastim (Hospira) and were monitored for 1–6 chemotherapy cycles, with 3 visits at inclusion, during, and following treatment. Results A total of 2114 patients were enrolled in this study; of these, 463 patients had breast cancer and were included in this analysis. Mean age was 58.4 years, 97% were female, 95.8% had an ECOG PS of 0–1, and 19.4% had metastatic disease. The majority of patients (n = 454; 98.1%) received biosimilar filgrastim as prophylaxis (primary, 94.1%; secondary, 5.9%); 9 (1.9%) patients received curative biosimilar filgrastim. Median time to initiation of biosimilar filgrastim was 7.5 days for curative patients and 4 days for prophylactic patients. Mean treatment duration was: 6.0±1.7 days (curative) and 5.6±2.6 days (prophylactic). Biosimilar filgrastim-related adverse events (AEs) were reported in 119 patients (curative, n = 1; primary prophylaxis, n = 111; secondary prophylaxis, n = 7). The rate of AEs was higher in breast cancer patients (26.1%) compared with the entire NEXT study population with solid tumors (21.1%); similar rates of FN were reported but breast cancer patients had higher rates of AEs and bone and muscle pain compared with the total study population. Considering the prophylactic group only, 4.7% experienced FN and 1.6% reported an infection. The incidence of FN and/or infection resulted in hospitalization in 4.7% of patients (mean duration: 4.6±2.5 days), chemotherapy dose reduction in 2.7% of patients, and a delay of chemotherapy in 5.2% of patients. Conclusion These data demonstrate the safety and efficacy of biosimilar filgrastim in a real-world setting. The subanalysis illustrated that biosimilar filgrastim was effective and well tolerated in breast cancer patients in the curative and prophylactic setting. These results mirror those of the parent NEXT study, and show that biosimilar filgrastim is a valid alternative therapeutic option for chemotherapy-induced neutropenia in breast cancer patients. Citation Format: Albrand H, Kamioner D, Leprêtre S. Biosimilar filgrastim in the treatment of patients with breast cancer undergoing neutropenia-inducing chemotherapy: A subanalysis of the NEXT study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-03.

ChemInform Abstract: Synthesis and Biological Applications of Hydroxamates

AbstractReview: 146 refs.

The Experience of Gruppo Laziale for the Study of Ph-, Chronic Myeloproliferative Syndromes in the Treatment of Myeloproliferative Neoplasms in Blastic Phase with Azacytidine

Prognosis of patients with myeloproliferative neoplasms developing blast phase (MPN-BP) is very poor with a median survival of about 2-3 months; nowadays, no treatment can induce a durable complete response (CR) in patients who are not candidate to BMT. Very recently, a possible role of azacytidine (AZA) was reported in these patients, but there is still a lack of data as to its efficacy; to address this issue, we evaluated retrospectively 19 patients (M/F 15/4 F, median age 71.3 years, interquartile range (IQR) 64.5 – 77.7] with MPN-BP treated with AZA and collected in the database of our cooperative group. The primary MPN diagnosis was Essential Thrombocythemia in 6 cases (31,6%), Policythemia Vera in 3 (15,8%), Primary Myelofibrosis in 7 (36,8%) and MDS/MPN in 3 (15,8%); the JAK-2 V617F mutation was present in 11/17 patients tested (64.7%). All but 1 patient received previous chemotherapies during chronic phase. Median time from diagnosis to BP evolution was 52.6 months (IQR 11.2 – 181.8). All patients were treated with AZA at the standard dosage of 75 mg/m2: 16 patients received a 7-day schedule and 3 a 5-day schedule every 28 days. Two patients died early after 5-AZA initiation for pulmonary fungal infection and respiratory failure respectively, 4 patients had a disease progression, 4 patients maintained stable disease, 3 patients had a hematological improvement, 1 patient achieved partial response and 5 patients (26.3%) a CR after 4, 4, 4, 5, and 12 months. The median cumulative survival from BP evolution was 9.9 months (95%CI 6.7 – 13.1).A comparison with the historical cohort of 72 patients of our database presenting MPN-BP and treated with approaches other than AZA (median cumulative survival 3.1 months, 95%CI 1.1 – 5.1) showed a significant advantage for patients treated with AZA (p= 0.02). Our data confirm the relative good efficacy and safety of AZA in this group of patients with otherwise dismal prognosis, underlining the possible achievement of long-lasting responses in a sizeable portion of them. DisclosuresNo relevant conflicts of interest to declare.

Safety of Biosimilar Filgrastim in Patients with Haematological Malignancies Undergoing Neutropenia-Inducing Chemotherapy: A Subanalysis of the Next Study

IntroductionFebrile neutropenia (FN) is a major risk factor for infection-related morbidity/mortality as well as a dose-limiting toxicity in patients (pts) undergoing chemotherapy (CT). Biosimilar filgrastim (Nivestim™, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. The NEXT (Nivestim™ safety profile in patiEnts treated with cytotoXic CT in real-life clinical pracTice) study aimed to assess the safety of biosimilar filgrastim in pts undergoing CT for malignancies.MethodsThe NEXT study was a prospective, observational, non-interventional, longitudinal, national, multicentre study conducted in France. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Adult pts (n=2114) undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as prophylaxis, or as curative treatment, were included. Data collected included pt characteristics, biosimilar filgrastim treatment-related data and treatment emergent AEs, including FN. Pts were monitored for 1–6 CT cycles at three visits: inclusion, a follow-up visit during treatment and the final visit following CT. Here we present data for pts with haematological malignancies.ResultsOf the pts analysed, 525 had haematological malignancies (chronic lymphoid leukaemia [CLL]/acute lymphoid leukaemia [ALL]: 70; lymphoma: 408; myeloma: 47). Overall, the mean age ± standard deviation (SD) of pts with haematological malignancies was 64.8 ± 15.4 years (64.4% male). At inclusion, 88.0% of pts had no prior FN (CLL/ALL: 88.6%; lymphoma: 89.2%; myeloma: 76.6%); 31.1% had prior CT (CLL/ALL: 32.9%; lymphoma: 27.5%; myeloma: 59.6%) and 27.1% had prior G-CSF therapy (CLL/ALL: 21.4%; lymphoma: 26.7%; myeloma: 38.3%). Of the pts prescribed a prior G-CSF therapy, 39.2% received biosimilar filgrastim. The majority of pts (98.9%) received biosimilar filgrastim prophylactically (CLL/ALL: 100.0%; lymphoma: 98.8%; myeloma: 97.9%).Of the group receiving biosimilar filgrastim with curative intent, the median time to initiation of biosimilar filgrastim therapy was 14.0 days after the start of the last CT cycle (lymphoma: 14.0 days; myeloma: 14.0 days); mean treatment duration ± SD was 4.8 ± 1.6 days (lymphoma: 5.2 ± 1.5 days; myeloma: 3.0 ± 0.0 days). In this group, 50.0% of pts received a dose of 30 MIU (lymphoma: 40.0%; myeloma: 100.0%) and biosimilar filgrastim was administered subcutaneously in all pts.In the prophylactic biosimilar filgrastim group, the median time to initiation of biosimilar filgrastim was 6 days after start of the last CT cycle (CLL/ALL: 6.0 days; lymphoma: 6.0 days; myeloma: 6.5 days); mean treatment duration ± SD was 6.7 ± 4.6 days (CLL/ALL: 7.5 ± 7.0 days; lymphoma: 6.6 ± 4.0 days; myeloma: 5.9 ± 4.5 days). In this group, 70.9% of pts received a dose of 30 MIU (CLL/ALL: 57.1%; lymphoma: 72.5%; myeloma: 78.3%) and biosimilar filgrastim was administered subcutaneously in all pts. Anti-infective prophylaxis was reported in 51.2% of pts (CLL/ALL: 88.6%; lymphoma: 42.9%; myeloma: 67.4%). In the prophylactic group, 7.5% (95% confidence interval [CI] 5.5, 10.1) experienced FN (CLL/ALL: 7.1% [2.7, 16.0]; lymphoma: 7.1% [4.9, 10.1]; myeloma: 10.9% [4.3, 23.5]).Of the pts with haematological malignancies, 18.6% experienced ≥1 AE (CLL/ALL: 8.6%; lymphoma: 21.5%; myeloma: 8.5%). The most common AEs (>5.0% of pts) were bone/muscular disorders (total: 13.7% [CLL/ALL: 7.1%, lymphoma: 16.0% myeloma: 4.3%]) and muscle pain (total: 13.4% [CLL/ALL: 7.1%, lymphoma: 15.5% myeloma: 4.3%]). In this analysis, 7.5% of pts were hospitalised for FN and/or infection (CLL/ALL: 7.1%; lymphoma: 7.1%; myeloma: 10.9%). The mean duration of hospitalisation ± SD for FN and/or infection after the first CT cycle was 11.3 ± 16.2 days (CLL/ALL: 10.5 ± 6.4 days; lymphoma: 11.4 ± 17.4 days; myeloma: 0.0 ± 0.0 days), 3.4% of pts had a CT dose reduction (CLL/ALL: 2.1%; lymphoma: 2.8%; myeloma: 2.3%) and 7.7% of pts (CLL/ALL: 15.7%; lymphoma: 5.9%; myeloma: 11.4%) had a delay in administration of CT due to FN and/or infection.ConclusionBiosimilar filgrastim was effective and well-tolerated in pts undergoing CT for haematological malignancies and is an alternative therapeutic option for pts with CT-induced neutropenia. DisclosuresMaloisel:Pfizer: Research Funding; Novartis: Research Funding; Hospira: Research Funding; Amgen: Research Funding. Albrand:Hospira: Employment.

Good Usage of Biosimilar Filgrastim: A Subanalysis of the Next Study

▪IntroductionFebrile neutropenia (FN), a major risk factor for morbidity/mortality, is associated with dose delays and/or reductions in potentially cytotoxic chemotherapy (CT) regimens. It is defined as an oral temperature >38.5°C, or two consecutive readings of >38.0°C for 2 h, with an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L. Guidelines from the European Organisation for Research and Treatment of Cancer (EORTC) recommend prophylactic use of granulocyte-colony stimulating factor (G-CSF) when using a CT regimen associated with a >20% risk of FN or in less intensive CT regimens if certain risk factors (eg >65 years, advanced disease, history of prior FN) are present. Biosimilar filgrastim (Nivestim™, Hospira Inc.) is a G-CSF licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. As the NEXT (Nivestim™ safety profile in patiEnts treated with cytotoXic chemotherapy in real-life clinical pracTice) study was conducted in France, the real-life usage of biosimilar filgrastim is compared with that recommended by current EORTC guidelines.MethodsThe NEXT study was a prospective, non-interventional, longitudinal, multicentre, national study. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Secondary objectives included the description of patients (pts) treated with, and patterns of use of, biosimilar filgrastim.Adult pts undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as primary or secondary prophylaxis, or as curative treatment, were included. The subanalysis presented here included only pts receiving prophylactic biosimilar filgrastim. Data were recorded on case report forms and included pt characteristics (demographics, medical history, CT-related data), biosimilar filgrastim treatment-related data (indication, dose, route of administration, treatment initiation) and treatment-emergent AEs, including FN. Individual FN risk factors were analysed. Pts were monitored for 1–6 CT cycles at three visits: inclusion, a follow-up visit during treatment and the final visit following CT.ResultsOverall, 2102 pts were included in the study analysis and 2065 pts received prophylactic biosimilar filgrastim. At inclusion, 73.9% of pts had no prior FN. Of the pts included in this analysis, 19.4% received CT associated with a high risk of developing FN (intermediate risk: 55.6%; low risk: 25.0%). Of the pts receiving CT regimens associated with an intermediate risk of FN, 95.4% had ≥1 risk factor for FN and of those receiving a regimen associated with a low risk of FN, 96.5% had ≥1 FN risk factor (Table 1).Of all pts receiving prophylactic biosimilar filgrastim, 3.5% developed FN after the first CT cycle, 1.8% developed an infection and 2.4% were hospitalised for FN and/or infection after the first CT cycle. Median time to initiation of biosimilar filgrastim was 2 days after the last CT dose; mean treatment duration ± SD was 6.0±3.8 days. Anti-infective prophylaxis was reported in 14.5% of pts.ConclusionThe majority of pts received prophylactic biosimilar filgrastim according to EORTC guidelines (ie either had >20% risk of FN or had ≥1 FN risk factor). Biosimilar filgrastim (Nivestim™) is an alternative therapeutic option for pts with prophylactic CT-induced neutropenia.Table 1Proportion of patients with risk factors for FNRisk factorPatients (%)Chemotherapy regimen associated with a high risk(>20%) of FNChemotherapy regimen associated with an intermediate risk (10–20%) of FNChemotherapy regimen associated with a low risk(<10%) of FNFemale51.558.647.9Age >65 years35.940.255.9Advanced disease40.441.966.4≥1 severe comorbidity25.627.535.2Poor nutritional status*3.83.17.0WHO performance grade ≥30.00.10.3Haemoglobin <12 g/dL at inclusion37.739.150.9Concomitant radiotherapy2.32.85.0Prior FN7.66.111.5*Defined as a body mass index <18.5 kg/m2WHO, World Health Organization DisclosuresMaloisel:Pfizer: Research Funding; Novartis: Research Funding; Hospira: Research Funding; Amgen: Research Funding. Albrand:Hospira: Employment.

Safety of Biosimilar Filgrastim in Patients Undergoing Neutropenia-Inducing Chemotherapy: The Next Study

▪IntroductionFebrile neutropenia (FN) is a frequent and potentially serious complication of cytotoxic chemotherapy (CT). It is defined as an oral temperature >38.5°C, or two consecutive readings of >38.0°C for 2 h, with an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L. Biosimilar filgrastim (Nivestim™, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) approved in France for the treatment of neutropenia and FN resulting from myelosuppressive CT. Previous clinical trials have demonstrated that the efficacy and safety of biosimilar filgrastim are similar to the reference product (Neupogen®, Amgen Inc). The NEXT (Nivestim™ safety profile in patiEnts treated with cytotoXic chemotherapy in real-life clinical pracTice) study aimed to confirm the safety of biosimilar filgrastim in patients (pts) undergoing cytotoxic CT for malignancies.MethodsThe NEXT study was a prospective, non-interventional, longitudinal, multicentre study conducted in France. The primary objective was to evaluate the safety of biosimilar filgrastim by gathering adverse event (AE) data. Secondary objectives included the description of pts treated with, and patterns of use of, biosimilar filgrastim.Adult pts undergoing cytotoxic CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as primary or secondary prophylaxis, or as curative treatment, were included. Data were recorded on case report forms and included pt characteristics (demographics, medical history, CT-related data), biosimilar filgrastim treatment-related data (indication, dose, route of administration, treatment initiation) and treatment emergent AEs, including FN. Pts were monitored for 1–6 CT cycles at three visits: baseline, follow-ups during treatment and the final visit following CT.ResultsOf 2114 pts enrolled in the study, 2102 pts were included in the study analysis (50.2% male). Baseline demographics included, mean age ± standard deviation (SD) was 63.5±12.7 years, 75.0% of pts had solid tumours and 25.0% had haematological malignancies (lymphoma: 19.3%; myeloma: 2.2%; acute leukaemia: 0.2%; chronic lymphocytic leukaemia: 3.1% other haematological malignancies: 0.1%). At baseline, 92.5% of pts had no prior FN; 34.4% had previous CT; 20.2% had received previous G-CSF therapy. The majority (98.2%) of pts received prophylactic biosimilar filgrastim (primary prophylaxis: 8.2%; secondary prophylaxis: 90.1%). Of the pts receiving prophylactic biosimilar filgrastim, 79.9% received a dose of 30 MIU and therapy was administered subcutaneously in 99.4% of these pts. In the prophylactic biosimilar filgrastim group, the median time to initiation of biosimilar filgrastim was 2 days after the last CT dose; mean treatment duration ± SD was 6.0±3.8 days. Anti-infective prophylaxis was reported in 14.5% of these pts.During the study 20.4% of pts experienced ≥1 AE; AEs were reported most frequently in pts with acute leukaemia (40.0%), lymphoma (21.6%) and solid tumours (21.1%). 12.7% of pts reported bone, muscular or chest pain. The other most common AEs included gastrointestinal disorders (5.5%), nausea (3.0%), general disorders and administration site disorders (2.4%), diarrhoea (2.3%) and headache (1.8%).Of the 2114 pts enrolled, the incidence of FN was 4.9% (95% confidence interval [CI] 4.06, 5.98) and 3.1% (95% CI 2.39, 3.93) of pts experienced an infection. Mean duration of hospitalisation ± SD for FN and/or infection after the first CT cycle was 8.7±10.9 days. Overall, 4.7% of pts had ≥1 CT dose reduction and 7.4% of pts had a delay in administration of CT due to FN and/or infection.ConclusionThese results provide further clinical evidence that biosimilar filgrastim (Nivestim™) is safe and effective in treating and preventing neutropenia and febrile neutropenia in pts receiving cytotoxic CT for haematological malignancies and solid tumours. These data continue to support a similar clinical safety and efficacy profile of biosimilar filgrastim (Nivestim™) compared with the reference filgrastim (Neupogen®, Amgen). Biosimilar filgrastim (Nivestim™) is an alternative therapeutic option for pts with prophylactic or curative CT-induced neutropenia. DisclosuresMaloisel:Pfizer: Research Funding; Novartis: Research Funding; Hospira: Research Funding; Amgen: Research Funding. Albrand:Hospira: Employment.

Safety of biosimilar filgrastim in patients undergoing neutropenia-inducing chemotherapy: Next study.

211 Background: Febrile neutropenia (FN) is a serious, frequent complication of cytotoxic chemotherapy (CT). Biosimilar filgrastim (Nivestim, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF) licensed for the treatment of neutropenia and FN induced by myelosuppressive CT. The NEXT (Nivestim safety profile in patients [pts] treated with cytotoxic CT in real-life clinical practice) study aimed to assess the safety of biosimilar filgrastim in pts undergoing CT for malignancies (excluding chronic myeloproliferative and myelodysplastic syndrome) and receiving biosimilar filgrastim as prophylaxis, or as curative treatment. Methods: NEXT was a prospective, non-interventional, longitudinal, multicentre study conducted in France. Recorded data included pt demographic and clinical characteristics, biosimilar filgrastim treatment-related data on efficacy and safety, such as adverse events (AEs), including FN. Pts were monitored for 1–6 CT cycles with three visits at inclusion, during treatment, and following CT. Results: Overall, 2114 pts were enrolled in the study. Of these, 2,102 pts were analysed (50.2% male). Mean age ± SD was 63.5 ± 12.7 years. 75% of pts had solid tumours and 25% had haematological malignancies. The majority (98.2%) of pts received prophylactic biosimilar filgrastim and 1.8% for curative intent. At inclusion, 92.5% of patients had no prior FN; 34.4% had prior CT; 20.2% had prior G-CSF therapy. During the study 20.4% of pts experienced ≥1 AE; AEs were reported most frequently in pts with acute leukaemia (40.0%), lymphoma (21.9%) and solid tumours (21.1%). 12.7% of pts reported bone, muscular or chest pain. 4.9% of pts experienced FN and 3.1% had an infection. Conclusions: Biosimilar filgrastim (Nivestim) was effective and well-tolerated in both the prophylactic and curative setting in pts undergoing CT for solid tumours and haematological malignancies. Biosimilar filgrastim seems to be as efficacious and as well tolerated compared with the reference filgrastim (Neupogen, Amgen) regarding retrospective data. Clinical trial information: NCT01574235.

Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib

AbstractMyeloid neoplasms and eosinophilia with rearrangements of PDGFRB are uncommon Philadelphia-negative myeloproliferative neoplasms. Patients are typically male, with morphologic features of a Philadelphia-negative chronic myeloproliferative syndrome or chronic myelomonocytic leukemia with eosinophilia. Reciprocal translocations involving PDGFRB result in fusion genes with constitutively activated receptor tyrosine kinase sensitive to inhibition with imatinib. We present an updated and expanded analysis of a cohort of 26 such patients treated with imatinib. After a median follow-up of 10.2 years (range, 1.8-17 years), the 10-year overall survival rate was 90% (95% confidence interval, 64%-97%); after median imatinib duration of 6.6 years (range, 0.1-12 years), the 6-year progression-free survival rate was 88% (95% confidence interval, 65%-96%). Of the patients, 96% responded; no patients who achieved a complete cytogenetic (n = 13) or molecular (n = 8) remission lost their response or progressed to blast crisis. Imatinib is well-tolerated and achieves excellent long-term responses in patients with PDGFRB rearrangements.

Detection of Jak2 V617f Mutation, Secondary to the Presence of Bcr-Abl1 Translocation in a Patient with Chronic Myeloid Leukemia: Report of a Case and Review of the Literature

The myeloproliferative neoplasms are classified in four major diseases: Chronic Myeloid Leukemia, Polycythemia Vera, Primary Myelofibrosis and Essential Thrombocythemia. The JAK2 V617F mutation is found in 95% of Polycythemia Vera, and 50% of Essential Thrombocythemia and Primary Myelofibrosis patients. It was thought that the JAK2 V617F mutation and BCR-ABL1 translocation were mutually exclusive; but now a few cases have been reported with both alterations. We report a rare case with the presence of JAK2 V617F mutation, secondary to a diagnosis of BCR-ABL positive chronic myeloid leukemia. The patient was initially diagnosed as chronic myeloid leukemia and was BCR-ABL1 positive, so he started to receive Imatinib. He responded well to the therapy for three years, but after this time the patient had a hematological relapse still with no detectable copies of BCR-ABL1. For this reason, we thought of the possible development of another genetic alteration. Because the patient had a very high platelet count, we decided to look for the JAK2 V617F mutation, which result was positive. This case is just one of the few that have been reported worldwide that have a coexistence of these two genetic alterations: the BCR-ABL1 transcript and JAK2 V617F mutation in chronic myeloproliferative syndromes. This is the first case in the Central American population, found in our series of a total of 168 patients with Philadelphia positive chronic myeloid leukemia.

Familial Essential Thrombocythemia Among Qatari Tribes

Essential thrombocythaemia (ET) is a chronic myeloproliferative syndrome due to sustained proliferation of megakaryocytes,which results in elevated numbers of circulating platelets, thrombotic or haemorrhagic episodes and occasional leukaemic transformation.Familial essential thrombocythemia,also called hereditary or inherited thrombocythemia or thrombocytosis, is a rare disorder transmitted in an autosomal dominant with clinical presentation and complications resembling sporadic essential thrombocythaemia (ET).Mutations in the thrombopoietin (TPO) gene causing overproduction of TPO and elevated TPO serum levels familial essential thrombocythemia is a heterogeneous disorder as families have been described with an activating mutation in the gene for the TPO receptor (c-MPL), the thrombopoietin gene, a germline mutation in JAK2 V617I or without a mutation in any of these genesOccurrence of Essential thrombocythemia among arab population never been reported before. In this study, essential thrombocythemia is documented in 25 families from 5 major tribes in Qatar Familial cases were defined when two or more individuals within the same pedigree were affected with MPNs. Clinical records of affected relatives were reviewed systematically to confirm MPNs diagnosis. Patients without family history of were defined as having sporadic. MPNs Diagnosis of MPNs was made in accordance with the WHO criteria 2008Ninety eight members of both sexes from 18 to 62 years of age in three successive generations. The propositus had a persistent elevation of the platelet count, splenomegaly, a normal hemoglobin level, a normal white blood cell count, and abnormal platelet aggregation. Platelet arachidonic acid metabolites assayed by high-performance liquid chromatography and serum thrombopoietin levels were normal. Megakaryocytes were increased in number and size. Both mature and early immature megakaryocytes, but no atypical megakaryocytes, were identified by surface immunofluorescence. Bone marrow cultures showed normal myeloid and erythroid colony formation, and chromosome studies revealed a normal The analysis of mutations of JAK2 and MPL may improve our ability to identify these conditions. In a consecutive series of patients observed in our Institution from January 2011 to June 2013 total No of 300 MPNs patients were diagnosed, out of 300 patient, 119 had PV, 160 had ET, 15 had PMF and six patient had unclassified atypical MPN case. Out of 119 PV pts, 116 (97.4%) were positive for the JAK2 V617F mutation and 3 cases met the WHO criteria for PV but were negative for JAK2 V617F and JAK2 exon 12 mutations. Out of 160 ET pts, 80 (50%) were positive for JAK2 V617F, one had MPL S505N mutation and 79 cases met the WHO criteria for ET but were negative for both JAK2 617F and MPL mutations. Out of 15 PMF pts 5 (33.3%) were positive for JAK2 V617F and the unclassified case which was characterized by Deep Vein Thrombosis had JAK2 exon 13 mutation (R564L).25 Arab families were described as having familial ET (5 major tribes were screened )20 were having JAK2V617F positive in three consequetive generations ,4 families were having Familial ET in three generations but both Jak2v617F and MPL were negativeMPL S505N mutation was found in one family( Father and daughter).there was no difference in clinical presentation and response to therapy in sporadic versus familial cases. ConclusionIn our series of familial cases clinical presentation, therapeutic approach type and severity of complications were comparable to that of sporadic cases. Furthermore, the present study indicates the relevant possibility of familial MPNs, thus suggesting the opportunity of a detailed family history as part of the initial work-up of patients with MPNs; in addition it also suggests the usefulness of an accurate biological studies Disclosures:Yassin:qatar national research fund: Patents & Royalties, Research Funding. Al-Dewik:qatar national research fund: Patents & Royalties, Research Funding. Cassinat:qatar national research fund: Patents & Royalties, Research Funding.

Profil cytogénétique des leucémies myéloïdes aigues et chroniques

Introduction : Chronic and acute myeloid leukemia (CML and AML) are malignant homeopathy caused by the attack of a hematopoietic original cell and resulting in clonal proliferation. Chronic myeloid leukemia is a chronic myeloproliferative syndrome characterized by a dominant proliferation of granular lineage, a presence of almost specific chromosomal abnormality (Philadelphia chromosome Ph) or its molecular equivalent (bcr/abl rearrangement). It is also characterized by a clinical evolution in three steps: chronic, accelerated and acute processing. Materials and methods : The report is a retrospective study realized over a period of 3 years. It concerned karyotypes realized for patients with myeloproliferatifs syndromes. Our series accounted for 128 karyotypes, among which 86 requests within the CML and 42 requests for AML. Results : In the CML group, 51 % of the patients presented a chromosome Ph or one of its variants. These variants in our group were either translocations t (1,9,22) (q35, q34, q11) or t (3,9,22) (p21, q34, q11) or t (9,13,22) (q34, q34, q11). A case of double chromosome Ph and 9 cases of negative Ph were identified. In the MLA group, among the found chromosomal abnormalities, we had 5 cases of t (8,21) (q22, q22), a case for each of the following chromosomal aberrations: del (3), t (10,11), t (13,14), del (19), del(20) and t (13,17) with three abnormalities being at the same patient’s. Discussion : In more than 90 % of the cases, the CML is characterized by the presence of a chromosome marker in hematopoietic cells. The chromosome Philadelphia (Ph) which results from a mutual balanced translocation t (9; 22) (q34; q11) is visible in conventional cytogenetic. In our series, the chromosome Ph is present at 37 % of the patients. In case of acute processing, supernumerary abnormalities are identified such as trisomy 8, duplication of the Ph, isochromosome 17.The t (8,21) is the most frequent chromosomal abnormality in our series. Conclusion : During myeloproliferatifs syndromes, the chromosome study allows to forecast the prognosis of the disease and a better therapeutic follow up of the patients.

Risk Factors of GANCICLOVIR–RELATED Neutropenia After Allogeneic STEM CELL Transplantation: A Retrospective Monocenter Study On 547 Patients

AbstractAbstract 4186 Introduction:Cytomegalovirus (CMV) disease is a serious complication that may occur in the weeks or months following bone marrow transplantation. Therefore it must be treated as soon as positive CMV reactivation is noticed: pre-emptive therapy has demonstrated to improve survival among patients reactivating CMV after transplantation. However, GANCICLOVIR (GCV) as well as CMV infection itself involves a well-know marrow toxicity, notably neutropenia that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. So far, only two studies specifically identified risk factors and outcome of GCV –related neutropenia, finding low marrow cellularity between day 21 and 28, hyperbilirubinemia > 6mg/dl during the first 20 days, serum creatinine > 2mg/l after day 21, and absolute neutrophil count as predictive factors. However, transplantation has evolved in recent years, especially thanks to the reduce intensity conditioning (RIC) and supportive care. The present analysis aims at identifying risk factors of neutropenia among a large cohort of patients treated by pre-emptive GCV who received allogeneic stem cell transplantation at our Institution over last years. Patients and Methods:This is a retrospective study on a cohort of 547 consecutive patients allografted from January 2005 to June 2011 at our Institution. Diagnoses were: acute myeloid and lymphoblastic leukemia, non-Hodgkin’s lymphoma, Hodgkin’s disease, chronic lymphocytic leukemia, myeloproliferative and myelodisplasic syndromes, aplastic anemia, metastatic solid tumor. Transplants were performed using three sources: bone marrow, peripheral blood stem cells, cord blood; patients receiving haploidentical transplant were excluded. Donors were HLA-sibling and matched or mismatched unrelated ones. Myeloablative, non-myeloablative and RIC regiments were administered according to local guidelines or established protocols. The principal objective of the study was to identify factors associated with the occurrence of grade 3–4 neutropenia among patients receiving antiviral therapy due to CMV reactivation. Secondarily, overall survival (OS), transplant-related mortality (TRM) and relapse/progression were analyzed and compared between patients who reactivated CMV vs. those who did not. Results:A total of 547 patients were included in the analysis. One hundred ninety patients presented CMV reactivation (34.7%). Thirty patients were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally one hundred and sixty patients were analyzed. We found that ANC above 3000 is a protective factor, (HR= 0.26, CI 95 %, 0.125–0.545, p < 0001); creatinine <2ml/dl after 21 days is a risk factor for GCV- related neutropenia (HR= 2.4, CI 95%, 1.11 – 5.17, p = 0.002) as well as a high viral load (HR=2.68, CI 95%, 1.25–5.737, p = 0.01). Using landmark analysis at day +100, overall survival (OS) at five years is lower for patients with CMV reactivation 43% (32–54) vs. 57% (46–68), p<0.0001. As concerns treatment-related mortality (TRM), we found a higher TRM among patients who developed CMV reactivation: 29% (21–36) vs. 12% (8–17), p=0.003. There is no significant difference in the risk of relapse in patients who reactivated CMV vs. those who did not reactivate 32 % vs. 34 % (p=n.s.).In conclusion, this large analysis revealed three risk factors of GCV-related neutropenia among patients with CMV reactivation after allogeneic hematopoietic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, thus potentially reducing morbidity and mortality associated with CMV reactivation. Disclosures:No relevant conflicts of interest to declare.