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Qiuying Liu,1 Nicholas Harris,1 Narendranath Epperla,2 Leslie A Andritsos1,3 1Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA; 2Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; 3University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USACorrespondence: Leslie A AndritsosUniversity of New Mexico, 1201 Camino de Salud, Albuquerque, NM, 87102, USATel +1-505-925-0405Fax +1-505-925-0408Email landritsos@salud.unm.eduAbstract: Hairy cell leukemia variant (HCL-v) is a rare B-cell lymphoproliferative disorder with distinct immunophenotypic and molecular characteristics when compared to classical hairy cell leukemia (HCL-c). In contrast to the enormous progress in therapeutic options for HCL-c, HCL-v remains a therapeutic challenge due to inferior outcomes with standard chemoimmunotherapy and BCR signaling pathway inhibitors, and due to the fact that HCL-v has limited molecular therapeutic targets. In addition, because of the rarity of the disease, there is a paucity of later phase studies or multicenter trials to guide treatment decisions. In this article, we briefly review the diagnostic criteria and clinical characteristics of HCL-v and present a comprehensive overview of current therapeutic options in HCL-v.Keywords: salvage therapy, rare lymphoid malignancies, HCL-v, HCL-c

Additional file 4: Table S4. GLM-adjusted follow-up outcomes among opportunistic infection sub-cohorts.

Additional file 2: Table S2. List of PNA-related adverse events and corresponding ICD-9-CM Codes.

Additional file 1: Table S1. Baseline individual comorbidities and corresponding ICD-9-CM codes.

Additional file 3: Table S3. GLM-adjusted follow-up outcomes among myelosuppression sub-cohorts.

Shashank Cingam,1 Lainey Flatow-Trujillo,2 Leslie A Andritsos,1 Cecilia Arana Yi1 1University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA; 2Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM, USACorrespondence: Cecilia Arana YiUniversity of New Mexico Comprehensive Cancer Center, 1201 Camino De Salud NE, Albuquerque, NM 87131, USAEmail caranayi@salud.unm.eduAbstract: Polycythemia vera (PV) is a rare myeloproliferative neoplasm (MPN) associated with significant impairment in quality of life (QoL) due to disease-related symptoms and complications. Assessment of disease burden constitutes standard monitoring of symptoms and response. Conventional treatments for MPN, such as hydroxyurea, phlebotomy, or interferon, have not shown a significant impact in QoL or patient-reported outcomes (PRO). Ruxolitinib (RUX) is a JAK2 inhibitor approved for patients intolerant or resistant to hydroxyurea (HA). We conducted a systematic review of clinical trials of RUX in patients with PV that incorporated PRO measures to evaluate the effects on PRO and QoL. Three randomized Phase 3 studies reported in four publications were relevant for analysis. Although the small number of trials and potential for treatment bias in the review, treatment with RUX was associated with improved QoL and PRO in PV patients intolerant or resistant to hydroxyurea.Keywords: polycythemia vera, ruxolitinib, quality of life, patient-reported outcomes

On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor - T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AICs). Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase approved for the treatment of relapsed CLL and CLL with del(17p). The effect of ibrutinib treatment on the incidence of AIC is currently unknown. We reviewed medical records of 301 patients treated with ibrutinib, as participants in therapeutic clinical trials at The Ohio State University Comprehensive Cancer Center between July 2010 and July 2014. Subjects were reviewed with respect to past history of AIC, and treatment-emergent AIC cases were identified. Before starting ibrutinib treatment, 26% of patients had experienced AIC. Information was available for a total of 468 patient-years of ibrutinib exposure, during which there were six cases of treatment-emergent AIC. This corresponds to an estimated incidence rate of 13 episodes for every 1000 patient-years of ibrutinib treatment. We further identified 22 patients receiving therapy for AIC at the time ibrutinib was started. Of these 22 patients, 19 were able to discontinue AIC therapy. We found that ibrutinib treatment is associated with a low rate of treatment-emergent AIC. Patients with an existing AIC have been successfully treated with ibrutinib and subsequently discontinued AIC therapy.

The impact of rhinovirus in hematopoietic SCT (HSCT) recipients is not well defined. A retrospective, matched, case-control study of HSCT recipients with rhinovirus was conducted between 2009 and 2011. Controls were matched for timing relative to transplant, malignancy, and stem cell source. There were 47 cases and 94 controls. The cases and controls did not differ with respect to age, gender, ethnicity, donor source, malignancy, conditioning regimen, immunosuppression, antimicrobial prophylaxis or significant comorbidities. There were no differences in need for intensive care unit care, 100 day mortality, hospice discharge, relapse of disease, GVHD or development of disease or infection due to CMV or EBV. Other infectious complications after rhinovirus diagnosis were also equal. However, there was an increased number of recurrent hospitalizations from any cause among the cases (46.8% vs 24.5%, P=0.007). Recurrent hospitalizations due to any infection were also more common in cases (34% vs 14.9%, P=0.015). For patients who were diagnosed with rhinovirus pre-transplant (n=13), there was no difference in outcome compared with matched controls. HSCT recipients with rhinovirus have an increased risk of hospital readmission. However, there was no difference in outcome compared with matched controls. Transplantation in patients with active rhinovirus infection appears to be safe.

Central nervous system (CNS) involvement by chronic lymphocytic leukemia (CLL) can present with dramatic neurologic findings or can be quite subtle, discovered only at the time of autopsy. We describe a case of CLL in a patient who presented initially with hearing loss and was ultimately found to have involvement of the tympanic membrane. She noted improvement of her hearing after induction therapy but was not aware at the time of the involvement of her CNS with CLL. Upon worsening of hearing at the time of relapse, she was evaluated by imaging and CSF analysis as well as biopsy of the tympanic membrane, and involvement of the CNS was confirmed. She has received CNS-directed therapy with intrathecal liposomal cytarabine and intravenous CNS-directed therapy and has noted improved hearing and resolution of her imaging and CSF findings. This is the first reported case of tympanic membrane involvement with CLL and describes potentially effective methods for managing this challenging complication.

7577 Background: HCL is a rare indolent leukemia that is more common in men, with a 4:1 male predominance. To date, no studies have characterized the potential difference in outcomes of HCL between male and female patients. Hence, we sought to evaluate the outcomes of female HCL patients using the HCL-PDR. Methods: The HCL Foundation sponsored the development of HCL-PDR to characterize the clinical features and outcomes of this rare leukemia. HCL-PDR is an international multicenter PDR that includes patient, disease and treatment information abstracted from medical records. Adult patients enrolled in the HCL-PDR were included in the study. Female patients with HCL were the study population, with males as the comparator. The primary endpoint was the time to next treatment (TTNT) in females compared to males. Secondary endpoints included response rates (RR) and predictors of TTNT. Responses were categorized as: complete response (CR) including CR/CRu (CR unconfirmed)/HR (hematologic response), and partial response (PR), which included PR/PRu (PR unconfirmed)/pHR (partial HR). CRu was defined as no disease in bone marrow (BM) without available blood counts and HR as blood counts meeting criteria for HR, but no available BM. Cox proportional hazard models were used to estimate the hazard ratios for TTNT risk. Results: 357 patients were included: 265 males and 92 females. Table shows baseline characteristics stratified by sex. Among the patients who had disease status assessed after first treatment (n=224, males 169 and females 55), there was no significant difference in RR. However, females had significantly longer median TTNT (17.6 years) relative to males (8 years, HR 0.54, 95% CI 0.32-0.91, p=0.02) that remained significant after adjusting for other variables (RR and BRAF mutation) in multivariable analysis (HR 0.32, 95% CI 0.11-0.97, p=0.04). Factors predictive of longer TTNT include female sex and CR (HR.0.26, 95% CI 0.11-0.57, p=0.001). Conclusions: This is the first study to date reporting the clinical characteristics and outcomes in female HCL patients. The significantly longer TTNT in females compared to males may be related to factors such as underlying molecular features or hormonal influences. This finding needs to be explored further. [Table: see text]

On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.