Division Of Hematology Research Articles

Integrative holistic approaches for children, adolescents, and young adults with sickle cell disease: A single center experience

ContextPainful vaso-occlusive crises (VOCs) associated with sickle cell disease (SCD) are the most common cause of morbidity, hospitalizations, and poor quality of life. Additional symptoms such as sleep disturbances, fatigue, and stress are also common. Non-traditional approaches are often used by families, but concerns remain that patients may forgo standard of care effective therapies in favor of dangerous unproven alternatives. ObjectivesTo describe a single center experience related to a multidisciplinary integrative medicine clinic within the division of hematology dedicated to children and young adults with SCD. MethodsThe Sickle Cell Integrative Clinic at Children’s National Hospital services patients with SCD. The main goal of this clinic is to provide access to non-pharmacologic interventions, and to manage patients’ symptoms in a holistic manner along with standard of care management of SCD. This IRB approved study evaluated experiences of both patients and parents who attended this clinic. ResultsThirty-seven unique patients attended this clinic over 2 years and 31 participated in the study. After attending the SCD integrative clinic, the majority of patients reported integrative therapies to be an acceptable way of treating pain and believed these to be effective. Overall, the vast majority (88 %) of patients reported having a positive experience with the therapies offered in the clinic. None of the patients experienced any adverse events related to integrative therapies provided in the clinic. ConclusionOur experience suggests that encouraging conversations and offering safe and potentially effective integrative therapies alongside conventional SCD therapies under medical guidance allows patients to have an open discussion about their beliefs and treatment goals, improves patient satisfaction and can improve outcomes.

The relationship between red cell distribution width and prognostic scores in myelodysplastic syndrome

IntroductionThe myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes. Materials and methodsNinety-four MDS patients at the Aydın Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance. ResultsThe mean age of all the patients was 73 ± 10 years. Patients were observed for 41.88 ± 25 months. The mean RDW value for all cases was 15.5 ± 2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below). ConclusionAn increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.

Thrombocytopenia in a 7-day-old Male.

1. Lindy Zhang, MD*,† 2. Caroline DeBoer, MD†† 3. Alejandra Ellison-Barnes, MD‡ 4. Jessica Berger, MD‡‡ 5. Courtney E. Lawrence, MD*,¶ 6. Rosalyn W. Stewart, MD MS MBA‡,§ 7. Lydia H. Pecker, MD** 1. *Departments of Pediatric Hematology, 2. †Pediatric Oncology, 3. ‡Internal Medicine, and 4. §Pediatrics and 5. ¶Division of Transfusion Medicine, Department of Pathology, and 6. **Division of Hematology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD; 7. ††Advocate Aurora Healthcare, Milwaukee WI; 8. ‡‡Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA 1. Address correspondence to Lindy Zhang, MD, Charlotte R. Bloomberg Children’s Center, Johns Hopkins Hospital, 1800 Orleans St, Baltimore, MD 21287. E-mail: lindyzhang{at}jhmi.edu A term boy was born via elective, repeat cesarean delivery to a mother whose prenatal laboratory tests were positive for group B Streptococcus genital infection and negative for human immunodeficiency virus, syphilis, gonorrhea, and chlamydia infections, and showed immunity for rubella. He was the third child born to this mother. The mother had no other diagnosed illnesses, including autoimmune diseases. The cesarean delivery was complicated by extensive adhesions from previous deliveries, but the delivery was atraumatic for the infant. The infant weighed 3.81 kg (82nd percentile for age), and had ABO mismatch with his mother (mother’s blood type was O+, infant’s blood type was A+). By 20 hours of age, the infant developed indirect hyperbilirubinemia (total bilirubin, 7.9 mg/dL). This elevation in bilirubin levels was attributed to ABO isoimmunization. He received 12 hours of phototherapy delivered by a fiberoptic mattress and fluorescent bulbs on an overhead lamp. On postnatal day 2, he had a circumcision, which was complicated by bleeding and required cauterization with silver nitrate. The remainder of his hospital course was uneventful. He was discharged without any ongoing evidence of easy bruising or bleeding and was scheduled for close follow-up with his pediatrician. On postnatal day 6, the infant was presented for his first newborn visit to his pediatrician with jaundice. His total bilirubin level was 19.3 mg/dL. The pediatrician sent the infant to the emergency department for additional evaluation and treatment. There, the infant was found to have severe thrombocytopenia (platelet count, 35 K/mm3) and indirect hyperbilirubinemia (total bilirubin, 20.2 mg/dL; direct bilirubin, 0.3 mg/dL). Mild anemia was present (hemoglobin, 13.8 …

Therapeutic Plasma Exchange in Thyroid Storm Refractory to Conventional Treatment

Thyroid storm is a life-threatening condition with mortality rates reaching up to 20 to 30%. First-line treatment includes inhibition of thyroid hormone synthesis, prevention of release of preformed hormones, blocking of peripheral FT4 to FT3 conversion, enhancing hormone clearance, and definitive radioactive iodine ablation. However, in the presence of life-threatening adverse effects (e.g., agranulocytosis) and contraindications (e.g., fulminant hepatic failure), therapeutic plasma exchange (TPE) can be used to rapidly remove circulating thyroid hormones, antibodies, and cytokines in plasma; this is recommended by the American Society of Apheresis (ASFA) and the American Thyroid Association (ATA) as second-line treatment for thyroid storm. Here, we report a 49-year-old female with Graves’ disease admitted in our emergency room for a 6-week history of fever, weight loss, jaundice, exertional dyspnea, palpitations, and diarrhea. Her initial thyroid hormone levels were: FT4 64.35 (NV 9.01–19.05 pmol/L), FT3 23.91 (NV: 2.89–4.88 pmol/L), and TSH 0.00000 (NV: 0.35-4.94 mIU/L) and we managed her as a case of thyroid storm (Burch-Wartofsky score 70) by initiating high dose propylthiouracil. However, her sensorium deteriorated and serum bilirubin continued to rise from 307.2 on admission to 561.6 umol/L on the 5th hospital day (NV: 3 - 22 umol/L). TPE was performed after consultation with the Division of Hematology. Over the treatment course, her thyroid hormones normalized: FT4 13.18 pmol/L, FT3 2.30 pmol/L. However, despite TPE, her symptoms worsened and she became comatose, had hypotension despite vasopressors and developed new-onset atrial fibrillation. She expired on her 7th hospital day from multiorgan failure. TPE is effective in decreasing circulating thyroid hormone levels. However, it had no effect on clinically important outcomes as our patient still deteriorated and eventually succumbed. We still wrote and submitted this case report since if only successful cases were reported, the true effectiveness rate of TPE could not be determined.

Cancer treatment delays caused by the COVID-19 pandemic may not hinder outcomes.

Cancer treatment delays caused by the COVID-19 pandemic may not hinder outcomes.

First person – Samanta Sarti

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Samanta Sarti is first author on ‘Inducible modulation of miR-204 levels in a zebrafish melanoma model’, published in BiO. Samanta conducted the research described in this article while a PhD student in Laura Poliseno's lab at the Oncogenomics Unit Core Research Laboratory (CRL), ISPRO/Institute of Clinical Physiology (IFC), CNR, in Pisa, Italy. She is now a Postdoctoral researcher in the lab of Samuel Sidi in the Department of Medicine, Division of Hematology and Medical Oncology and Department of Cell, Developmental and Regenerative Biology, at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, investigating the role of miR-204 in melanoma development by its inducible modulation in a zebrafish melanoma model.

Venetoclax Has Modest Efficacy in the Treatment of Patients with Relapsed T-Cell Prolymphocytic Leukemia

Venetoclax Has Modest Efficacy in the Treatment of Patients with Relapsed T-Cell Prolymphocytic Leukemia

Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020.

Khot S, Park BS, Longstreth WT Jr. The Vietnam War and medical research: untold legacy of the U.S. Doctor Draft and the NIH “Yellow Berets”. Acad Med. 2011;86:502–8. Article Google Scholar Download references RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK Robert Peter Gale Department of Medicine, Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH, USA Hillard M. Lazarus Wake Forest University Comprehensive Cancer Center, Winston Salem, NC, USA Gordon L. Phillips II You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Robert Peter Gale. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Gale, R.P., Lazarus, H.M. & Phillips, G.L. Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020. Leukemia (2020). https://doi.org/10.1038/s41375-020-01027-x Download citation Received: 30 July 2020 Revised: 05 August 2020 Accepted: 11 August 2020 Published: 09 September 2020 DOI: https://doi.org/10.1038/s41375-020-01027-x

Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020

Khot S, Park BS, Longstreth WT Jr. The Vietnam War and medical research: untold legacy of the U.S. Doctor Draft and the NIH “Yellow Berets”. Acad Med. 2011;86:502–8. PubMed Article Google Scholar Download references RPG acknowledges support from the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme. Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London, UK Robert Peter Gale Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA Hillard M. Lazarus Wake Forest Comprehensive Cancer Center, Winston-Salem, NC, USA Gordon L. Phillips II You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Robert Peter Gale. The authors declare they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Gale, R.P., Lazarus, H.M. & Phillips, G.L. Roger Herschel Herzig: younger half of the dynamic duo which advanced leukaemia therapy and transplants: January 4, 1946 to July 18, 2020. Bone Marrow Transplant (2020). https://doi.org/10.1038/s41409-020-01055-2 Download citation Received: 30 July 2020 Revised: 14 August 2020 Accepted: 02 September 2020 Published: 09 September 2020 DOI: https://doi.org/10.1038/s41409-020-01055-2

MM-125: Assessment of Vitamin D Levels in Multiple Myeloma Patients Newly Diagnosed and After Treatment

Context: Vitamin D deficiency is extremely common in multiple myeloma (MM), with 40% of patients having vitamin D levels in the deficient range of levels less than 36 nmol/L, and it represents a surrogate feature for clinical multiple myeloma disease status. Objective: To compare vitamin D levels in newly diagnosed MM patients and those that received treatment. Design: Case-control study from July 2018 to July 2019. Setting: Clinical Hematology and Bone Marrow Transplantation Division of Internal Medicine Department, Ain Shams University, Cairo, Egypt. Patients and methods: A randomized sample of 60 participants enrolled, 20 are newly diagnosed multiple myeloma patients, 20 patients post-treatment and 20 age- and sex-matched apparently healthy volunteers as a control group. Serum 25-hydroxyvitamin D (25(OH) D) levels were measured by enzyme-linked immunoassay (ELISA) at diagnosis and after 12 weeks of treatment. Results: In the newly diagnosed group, 25% of subjects had vitamin D deficiency ( 30 ng/ml). In MM patients that received treatment, no patient had vitamin D deficiency, 65% had vitamin D insufficiency, and only 35% had sufficient levels. In control group; no vitamin D deficiency, 70% of subjects had vitamin D insufficiency, and 30% of subjects had sufficient levels, with statistically significant difference of vitamin D deficiency between newly diagnosed MM patients and those after treatment (p=0.024). Conclusion: Prevalence of vitamin D deficiency is higher amongst MM patients than that of controls. Moreover, it exhibits a relationship to disease status with lower values in newly diagnosed patients when compared to those that received treatment. This is suggesting the potential role of vitamin D in pathogenesis of MM.

Hematology and oncology clinical care during the coronavirus disease 2019 pandemic.

New York City has been at the epicenter of the coronavirus disease 2019 (COVID‐19) pandemic that has already infected over a million people and resulted in more than 70,000 deaths as of early May 2020 in the United States alone. This rapid and enormous influx of patients into the health care system has had profound effects on all aspects of health care, including the care of patients with cancer. In this report, the authors highlight the transformation they underwent within the Division of Hematology and Medical Oncology as they prepared for the COVID‐19 crisis in New York City. Under stressful and uncertain conditions, some of the many changes they enacted within their division included developing a regular line of communication among division leaders to ensure the development and implementation of a restructuring strategy, completely reconfiguring the inpatient and outpatient units, rapidly developing the ability to perform telemedicine video visits, and creating new COVID–rule‐out and COVID‐positive clinics for their patients. These changes allowed them to manage the storm while minimizing the disruption of important continuity of care to their patients with cancer. The authors hope that their experiences will be helpful to other oncology practices about to experience their own individual COVID‐19 crises.

Vitamin D Supplementation Improves Health-Related Quality of Life and Physical Performance in Children with Sickle Cell Disease and in Healthy Children.

No study determined if vitamin D supplementation improves health-related quality of life (HRQL) using pediatric Patient-Reported Outcomes Measurement Information System or physical functioning in type SS sickle cell disease (HbSS). Subjects with HbSS (n = 21) and healthy subjects (n = 23) were randomized to daily oral doses (4,000 vs. 7,000 IU) of cholecalciferol (vitamin D3) and evaluated at 6 and 12 weeks for changes in serum 25 hydroxyvitamin D (25(OH)D), HRQL, and physical functioning. In subjects with HbSS, significant reductions in pain, fatigue, and depressive symptoms and improved upper-extremity function were observed. In healthy subjects, significant reductions in fatigue and improved upper-extremity function were observed. Significant improvements in peak power and dorsiflexion isometric maximal voluntary contraction torques were observed in both groups. In subjects with HbSS, improved plantar flexion isometric maximal voluntary contraction torques were observed. Both groups saw significant improvement in their total Bruininks-Oseretsky Test of Motor Proficiency score. Daily high-dose vitamin D supplementation for African American children with and without HbSS improved HRQL and physical performance.

Vascular Access in Children With Blood Disorders or Cancer.

* Abbreviations: CVAD — : central venous access device miniMAGIC — : Michigan Appropriateness Guide for Intravenous Catheters in Pediatrics PICC — : peripherally inserted central catheter Children with disorders of blood and cancer frequently require long-term central venous access devices (CVADs) for recurrent blood draws, blood transfusions, and infusion of caustic medications, such as chemotherapy, immunotherapy, and biological agents. Their diagnosis puts them at increased risk for other comorbidities, such as systemic infection from neutropenia, along with thrombosis secondary to malignancy, immobility, chemotherapeutic agents (eg, steroids and asparaginase), or the underlying thrombogenic state of sickle cell disease.1–3 Therefore, careful consideration is needed when choosing a CVAD that is best for these patients. The guidelines/recommendations in this article are not American Academy of Pediatrics policy, and publication herein does not imply … Address correspondence to Julie Jaffray, MD, Division of Hematology, Oncology, and Bone Marrow Transplant, Department of Pediatrics, Children’s Hospital Los Angeles, 4650 Sunset Blvd, Mailstop #54, Los Angeles, CA 90027. E-mail: jjaffray{at}chla.usc.edu

Use of Chloroquine and Hydroxychloroquine in COVID-19 and Cardiovascular Implications: Understanding Safety Discrepancies to Improve Interpretation and Design of Clinical Trials.

Author(s): Oren, Ohad; Yang, Eric H; Gluckman, Ty J; Michos, Erin D; Blumenthal, Roger S; Gersh, Bernard J

Why Aren't People Living with HIV at Higher Risk for Developing Severe Coronavirus Disease 2019 (COVID-19)?

Why Aren't People Living with HIV at Higher Risk for Developing Severe Coronavirus Disease 2019 (COVID-19)?

Therapeutic Vulnerabilities in Acute Myeloid Leukemia (AML) with TP53 Alterations

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow with a low two‐year survival rate. Standard chemotherapy achieves complete remission in 60–80% of patients, but 20–30% patients relapse due to leukemia stem cells (LSCs) that can self‐renew and recapitulate disease. AML with TP53 alterations has a lower prognosis with survival rates of 0–10% at one year. In vitro drug screens have identified drugs to target AML, but none have studied the effect of these therapies on LSCs with TP53 alterations. These in vitro drug screens include Crizotinib, Elesclomol, AZD1480, GW2580, Venetoclax, and Entrectinib. Crizotinib, AZD1480, GW2580, Venetoclax, and Entrectinib are signaling pathway inhibitors. Elesclomol induces oxidative stress and apoptosis in cancer cells. The goal of this research is to understand the molecular mechanisms of self‐renewal and therapeutic vulnerabilities in LSCs of AML with TP53 alterations. Specifically, we investigate whether these agents target LSCs from AML with TP53 alterations. We performed in vitro viability and in vitro colony forming assays (CFAs) on primary human AML samples with TP53 alterations, plating them with drugs or vehicle control. Furthermore, we used CYTOF to assess the effects of each drug on signaling within leukemia subpopulations. Crizotinib proved to be effective in reducing in vitro viability, in vitro CFAs, and affecting the expression of immunophenotypic markers, such as CD34 and CD123, which are markers for leukemia stem cell populations. Our data reveals cell‐type specific effects of Crizotinib in human AML with TP53 alterations. Our findings suggest that Crizotinib may be an effective therapy for patients with AML with TP53 alterations.Support or Funding InformationThis research was supported and funded by: NIH/NIGMS MARC U* STAR T34 HHS 00026 National Research Service Award to UMBC, Summer Research at the University of Minnesota Medical School NIH HLBI 2R25HL088728‐11A1, Dr. Colin Campbell, Dr. Craig Henke, American Cancer Society Mentored Research Scholar Grant (MSRG‐16‐195‐01‐DDC), Frederick A. Deluca Foundation, CTSI K to R01 Award, NIH/NCATS, Lois and Richard King Assistant Professorship in Medicine, Division of Hematology, Oncology, Transplantation, Dept. of Medicine, University of Minnesota University of Minnesota Foundation Donors

Clinical problems and surgical interventions in inherited factor VII deficiency.

Aim:Factor VII deficiency is one of the hereditary coagulation disorders that has autosomal reccessive inheritance and is observed relatively frequently (1/500 000). It is clinically heterogeneous, and may be asymptomatic or lead to life-threatening bleeding. Thus, there is no correlation between FVII activity and clinical findings. Plasma-derived and recombinant FVII concentrates are currently used for treatment. In countries where access to these products is lacking, fresh frozen plasma and prothrombin complex concentrates are also used, though they contain low amounts of factor FVII. In this study, we present the clinical properties, treatments, and surgical interventions used in patients followed up in our clinic with a diagnosis of factor FVII deficiency.Material and Methods:Patients who were diagnosed as FVII deficiency in Division of Pediatric Hematology and Oncology between July 1997 and July 2018, were included in the study. The patients’ demographic characteristics, symptoms at presentation, PT, aPTT, and FVII values, types of bleeding, and treatments and surgical interventions used, were recorded. The bleedings observed in the patients were classified by severity as asymptomatic, minor, and major.Results:A total of 18 patients (7 girls and 11 boys) with a mean age of 9.64±9.63 years were included in the study. The mean follow-up time was found as 78.06±54.4 months. When the bleedings were classified clinically, no bleeding was observed in eight patients (44.4%). The factor FVII level was found as <10% in three of these eight asymptomatic patients and above 20% in the others. Minor bleeding was observed in nine patients (50%) and major bleeding was observed in one patient. When the patients were classified as asymptomatic and symptomatic, there was no significant difference between the two groups in terms of FVII level (p=0.57). A total of 21 surgical interventions were performed in 14 (78%) of 18 patients who were being followed up.Conclusion:FVII deficiency has a very wide spectrum both clinically and in terms of approach to surgical interventions. Therefore, patients with factor FVII deficiency should be followed up and treated by comprehensive care centers with close collaboration of multiple disciplines.

Finish before the start: Analyzing preanalytical sample errors in a tertiary care hematology laboratory

(a) To evaluate the types and frequencies of preanalytical errors occurring in a tertiary care hematology diagnostic center and (b) To evaluate differences if any, across groups [outpatient data (OPD) vs inpatient data (IPD), type of test requested [complete blood count (CBC) vs coagulation] and laboratory (routine vs emergency). A prospective study was conducted over a period of nine months (August 2017-April 2018) to address the above objectives. All samples received in the clinical hematology division of our institute were included in the analysis. Categories of preanalytical errors were defined. This included insufficient, clotted, diluted, and lipemic samples. Clerical errors such as wrong/absent sample labeling, requisition form-sample mismatch, and wrong vacutainer selection were also documented. IPD and OPD data, as well as data pertaining to samples sent for different tests [complete blood count (CBC)/coagulation] and in the routine and emergency laboratories, were segregated. All errors in each category were recorded as numbers and corresponding percentages (proportions). The two-tailed z-test was applied to assess the significance of the difference in proportions across all groups. Statistical significance was kept at P < 0.05. A total of 189,104 samples were received in the clinical hematology laboratory during the aforementioned period, out of which preanalytical errors were found in 4052 (2.14%) samples. Inadequate sample quantity (ISQ) comprised the bulk of preanalytical errors in our laboratory (1.11% of total samples) followed by sample clots (0.88%). There was no significant difference in the error frequencies in OPD and IPD (P = 0.1031). The proportion of errors was higher in routine vis-à -vis emergency samples and also in samples sent for coagulation analysis vis-à -vis CBC.

Patient Reported Outcomes (PROs) Show Superior Quality of Life (QOL) of Patients with Chronic Myeloid Leukemia (CML) Treated with First Compared to Newer Generations of Tyrosine Kinase Inhibitors (TKIs)

Background: Tyrosine kinase inhibitors (TKIs) prolong the survival of patients with chronic myeloid leukemia (CML). Nowadays, the life expectancy of these patients is approaching that of an age-matched population. Since imatinib, was first introduced 20 years ago, several newer more potent TKIs, have been approved for CML. While these drugs are effective, they come with the trade-off of adverse effects, some are common to all and some are drug-specific. Most patients will receive prolonged treatment, therefore quality of life (QOL) is becoming a major concern. QOL under these drugs has not been directly compared. Herein, we compared the QOL of patients with CML treated with imatinib, dasatinib and nilotinib using patient reported outcomes (PROs) questionnaire. Methods: This nationwide study was a joint initiative of the Israeli CML patients' organization and the division of hematology at Rabin Medical Center, Israel. Patients completed computerized questionnaires that were provided to us by the European Organization for Research and Treatment of Cancer (EORTC). The questionnaires included 30 items core questionnaire (QLQ-C30), 24 items of CML-specific questionnaire (QLQ-CML24) and additional items that were added by the researchers. Questioners are composed of functional, symptom and global health/QOL scales/items. All scales and single-item measures were standardized and the score ranges from 0 to 100. High score for functional and QOL items/scales represents better function and QOL. High score in symptoms items represents worse symptomatology. We used the Mann-Whitney test to compare medians and χ2 to compare categorical variables. Results: Overall, 195 patients completed the questionnaire. The median age was 58 years (range: 23 to 89) and of those 102 patients (59%) were males. Time from diagnosis ranged between less than a year and 46 years (median: 7 years). In the primary analysis we included 139 patients (71%) who received either imatinib (n = 70, 36%), dastainib (n = 45, 23%) or nilotinib (n = 24, 12%). We did not include the few patients who received bosutinib (n = 8, 4%), ponatinib (n = 2, 1%) or patients who discontinued treatment (n = 22, 11%). Patients on imatinib were older (median age 67 years, range : 32 to 89) compared with patients on either nilotinib (median age 50 years, range 26 to 85 ) or dasatinib (median age 47 years, range: 26 to 85) (P&lt;0.0001), but had similar demographics and disease characteristics. The EORTC questionnaires included 34 items related to symptoms experienced by patients within the last week. These items were grouped into 13 symptom scales. Overall, the symptomatic profile was more severe in patients who received either dasatinib or nilotinib compared with imatinib. For example, compared with patients who received dasitinib or nilotinib, patients on imatinib experienced lesser limitation on daily activities (38 and 47 vs. 25 respectively, P = 0.02), less fatigue (53 and 57 vs. 37 respectively, P = 0.001) and lesser degree of impaired body image (38 and 46 vs. 26 respectively, P = 0.022). Likewise, symptom burden score was 41 in patients on nilotinib, higher than in patients receiving dasatinib (27, P = 0.005) or imatinib (30, P = 0.018). In addition, patients on imatinib had less painful episodes compared with patients on nilotinib (28 vs. 47. P = 0.014). The questionnaire included also 18 items that were grouped into 8 scales which estimated their functional status. Compared with nilotinib, patients on imatinib had better emotional functioning (77 vs. 61, P = 0.009); patients were less worried, stressed depressed or nervous. Patients were also more satisfied of the knowledge and treatment they received by their caregivers (41 vs. 19 24, P = 0.01). Finally, although patients on imatinib were older, they reported better home and work function (67) compared with either nilotinib (50) or dasatinib (50) (P &lt; 0.001). Conclusions: Compared with nilotinib and dasatinib, patients who received imatinib reported lower levels of symptomatology. They reported less fatigue, limitation of daily activities, impaired body image and pain. They were also more satisfied by their caregiver, had better emotional functioning and were less worried, depressed or nervous. Since patients on 2nd generation TKIs were almost 2 decades younger, these differences reflect not only the TKI toxicity profile but also the generation-gap and the primary significance "Generation Y" gives to QOL issues. Disclosures Shacham: novartis: Consultancy. Sharf:Janssen: Other: Advocacy grants funding; Novartis: Honoraria, Other: Advocacy Advisory Board, Research Funding; Abbvie: Other: Advocacy grants funding; Takeda: Other: Advocacy grants funding; Incyte: Honoraria, Other: Advocacy Advisory Board, Research Funding; Pfizer: Honoraria, Other: Advocacy Advisory Board, Research Funding; BMS: Other: Advocacy grants funding, Research Funding; Roche: Other: Advocacy grants funding.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate &gt; 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.