Academic literature on the topic 'P 25.5 UL 2011 R888'

8067 Background: We studied the value of a proposed prognostic index (PI) generated by baseline absolute monocyte (AMC) and lymphocyte (ALC) counts for pts with DLBCL, using values as previously reported (Leukemia 25:1502-9, 2011). Methods: From 03/07 to 01/09, 245 consecutive pts with untreated DLBCL receiving standard R-CHOP from the MDACC database were evaluated. Baseline AMC and ALC were retrospectively recorded. High AMC (≥610/uL) and a low ALC (≤1000/uL) were examined as dichotomized variables for progression-free (PFS) and overall survival (OS). An AMLPI was generated, stratifying pts into 3 risk groups (RGs): low-(AMC <610/uL and ALC >1000/uL), intermediate-(AMC ≥610/uL or ALC ≤1000/uL), and high-risk(AMC ≥610/uL and ALC ≤1000/uL). The prognostic effect of the AMLPI and the IPI were examined by multivariate analysis (MVA). Results: Ninety (37%) had high AMC and 71 (29%) had low ALC. By univariate analysis, a high AMC was associated with inferior PFS (p=0.01) and OS (p=0.03). The frequencies of AMLPI RGs were: low-105 pts (43%), intermediate-119 (48%), and high risk-21 (9%). With a median follow-up of 22 months (range <1-42), 3-year PFS and OS rates for these RGs were 80%, 61%, and 46% (p=0.007) and 92%, 76%, and 60% (p=0.006), respectively. Three-year PFS rates for IPI 0-2 and 3-5 RGs were 73% and 58%, respectively (p=0.0004); comparable OS rates were 88% and 68%(p<0.0001). For pts with IPI 0-2, 1-year PFS rates for AMLPI low, intermediate, and high RGs were 92%, 89% and 80% (p=0.022); comparable 1-year OS rates were 96%, 95% and 80% (p=0.049). By MVA, AMLPI effect (low vs. high RGs) on PFS was significant (p=0.046) as was IPI effect (0-2 vs 3-5, p=0.005); similar results were observed for OS (p=0.052 and p=0.003, respectively). Conclusions: Baseline AMC and AMLPI are significant variables for PFS and OS for pts with DLBCL receiving R-CHOP. AMLPI can identify pts with low, intermediate, and high-risk disease for PFS and OS, particularly for those with IPI 0-2. AMLPI may also add prognostic value beyond that of the IPI.

نظرية الأهلية: دراسة تحليلية مقارنة بين الفقه وعلم النفس، هدى محمد حسن هلال، هيرندن: المعهد العالمي للفكر الإسلامي، 2011م، 340 صفحة. علم النفس والعولمة؛ رؤى مستقبلية في التربية والتنمية، مصطفى حجازي، القاهرة: المركز الثقافي العربي، 2010م، 335 صفحة. أزمة علماء النفس المسلمين، مالك بدري، عمان: مركز ديبونو لتعليم التفكير، 2010م، 84 صفحة. إسلامنا والتراث "نحو تقويم الخطاب الديني"، أحمد عبده ماهر، وأحمد عبد الرحيم السايح،خاص: أحمد عبده ماهر، 2010م، 280 صفحة. المعرفة والسلطة في التجربة الإسلامية "قراءة في نشأة علم الأصول ومقاصد الشريعة"، عبد المجيد الصغير، القاهرة: رؤية للنشر والتوزيع، 2010م، 616 صفحة. التبادل الاقتصادي وضبطه بمقاصد الشريعة: دراسة مقارنة، ثناء محمد إحسان الحافظ، بيروت: دار الفكر المعاصر، 2010م، 480 صفحة. الدليل المبسط في مقاصد الشريعة، محمد هاشم كمالي، هيرندن: المعهد العالمي للفكر الإسلامي، 2011م، 48 صفحة. مقاصد الشريعة: دليل للمبتدئ، جاسر عودة، هيرندن: المعهد العالمي للفكر الإسلامي، 2011م، 76 صفحة. Religion and Spirituality in Psychotherapy: An Individual Psychology Perspective, Thor Johansen, New York: Springer Publishing Company; 5 edition (December 7, 2009), 240 pages. Conceptions of Islamic Education: Pedagogical Framings (Global Studies in Education), Yusef Waghid, Switzerland: Peter Lang Publishing, First printing edition (May 25, 2011), 160 pages. Nature and Technology in the World Religions (A Discourse of the World Religions), P. Koslowski, Dordrecht, Netherlands: Kluwer Academic Publishers, (July 29, 2011), 166 pages. Imam Bukhari and the Love of the Prophet- pbuh, (Al-Hidayah Series), Muhammad Tahir-ul-Qadri, London: Minhaj-ul-Quran International (MQI), July 30, 2009, 148 pages. Hadith: Muhammad's Legacy in the Medieval and Modern World. Jonathan Brown, London: Oneworld (June 1, 2009), 304 pages. Light From the East: How the Science of Medieval Islam Helped to Shape the Western World, John Freely, London: B. Tauris (April 12, 2011), 256 pages. للحصول على كامل المقالة مجانا يرجى النّقر على ملف ال PDF في اعلى يمين الصفحة.

Abstract Abstract 1720 Background: The myelodysplastic syndromes are commonly divided into lower- and higher-risk subtypes depending on blast percentage and International Prognostic Scoring System (IPSS) score (0–1.0, low or Int-1, median overall survival (OS) 3.5–5.7 years). Because the IPSS is limited in its ability to identify poor prognosis lower-risk patients (pts), a prognostic scoring system specifically for lower-risk MDS pts (LR-PSS) was developed (Garcia-Manero Leukemia 2008) at MD Anderson (MDA), based on unfavorable (non-del(5q), non–diploid) cytogenetics, hemoglobin (hgb) <10g/dl, platelet count (plt) <50 k/uL or 50–200k/uL, bone marrow blast %≥4, and age ≥60 years. The IPSS-R (Greenberg Leuk Res 2011) improves upon the IPSS using novel cytogenetics classifications (Schanz EHA 2010) and a neutrophil cut-off of 800 k/uL. We validated the LR-PSS and the IPSS-R in a separate cohort of lower-risk MDS patients seen at Cleveland Clinic (CC) or at MDA not included in LR-PSS development. Methods: Of 1293 MDS patients identified at CC or MDA from 1991–2010, 664 had lower-risk disease and adequate data for analyses. OS was calculated from first date seen at either institution. The Kaplan–Meier method was used to estimate median OS. Univariable analyses were performed using the log-rank test; multivariable analyses used a Cox proportional hazards model stratified by treatment center. Harrell's c index and the Akaike information criteria (AIC) were used to assess the discriminatory power of the models and relative goodness of fit, respectively. Results: Comparing CC to MDA, baseline values were similar except median age: 70 vs. 67 years (p=.02); time since diagnosis: 2.7 vs. 1.1 months (p<.0001); hgb <10: 51% vs. 43% (p=.05); plt <50k/uL: 30 vs. 24% (p=.06); ANC <1.5 k/uL: 27% vs. 36% (p=.01); blasts <4%: 75% vs. 65% (p=.003); WHO classification RA/RARS/RCMD/CMML: 11/15/26/12% vs. 16/9/45/0% (p<.0001). Cytogenetics were diploid: 61% vs. 66%; del(5q): 9% vs. 2%; del(20q): 3% vs. 5%; -Y: 4% vs. 2%, respectively (p=.5). Median OS was 36.8 months (95% C.I. 33–45) and median follow-up of patients still alive was 13.9 months (range 0.01–155). LR-PSS and IPSS-R classifications for CC and MDA Pts and OS are in Table 1 and Figure 1. In univariable analyses, The IPSS, LR-PSS, and IPSS-R were all predictive of OS (p=.002, <.0001, and <.0001, respectively). Multivariable analyses confirmed the overall predictive abilities of the prognostic tools and of Hgb, plt, age, and IPSS/IPSS-R cytogenetics (all p≤.03). Compared to the IPSS-R, the LR-PSS had the higher (better) Harrell's c value (.64 vs.63) and lower (better) AIC (2518 vs. 2525). The LR-PSS upstaged 156 pts (25%) from IPSS low or Int-1 to LR-PSS Category 3, and downstaged 47 pts (12%) from Int-1 to Category 1. The IPSS-R upstaged 164 pts (27%) from IPSS low or Int-1 to IPSS-R Categories ≥Intermediate, and downstaged 5 pts (1%) from Int-1 to Very Good. Conclusions: The LR-PSS and IPSS-R are valid tools for distinguishing among pts previously thought to have lower-risk disease by the IPSS, and identifying those who have better and worse survival. This latter group of pts may benefit from earlier interventions with disease-modifying therapies, and should be considered in trials targeting higher-risk MDS pts. The LR-PSS appears to provide slightly better prognostic information. Disclosures: Sekeres: Celgene: Consultancy, Honoraria, Speakers Bureau. Maciejewski:Celgene: Membership on an entity's Board of Directors or advisory committees.

123 Background: Regulatory T cells are increased in melanoma pts and are postulated to impair objective response to immune therapies. Pembro blocks programmed death receptor-1, reverses T-cell suppression and induces antitumor activity. Continuous low dose TMZ has immunomodulatory effects resulting in selective CD4+ lymphopenia of which the T-reg population of CD4+/CD25+ T cells could be decreased significantly. TMZ has demonstrated dramatic responses after IL-2 in metastatic melanoma pts. We evaluated responses with sequential TMZ after progression on pembro in pts with metastatic melanoma. Methods: Medical records of pts with metastatic melanoma treated with pembro and TMZ at Holden Comprehensive Cancer Center between 1/1/2011 and 8/31/2016 were reviewed. Recorded data included BRAF mutation status, treatment doses, serological markers, duration of treatment and treatment related responses (immune RECIST and RECIST 1.1). Results: Overall 10 pts (7 males, 3 females) with metastatic melanoma received sequential pembro followed by TMZ after disease progression or unacceptable toxicity. Eight were BRAF negative and 7 were pretreated with ipilimumab. Median age at time of initiating pembro (2 mg/kg every 3 weeks) was 64 years (range 33-75). Pts received a median of 4 doses (2-19). Median duration of treatment was 88 days (41-464) with stable disease in 3, progressive disease (PD) in 6 and 1 not evaluable for response. All pts thereafter received TMZ (75 mg/m2 daily for 6 weeks on 8 week cycle except 1 who received 200 mg/m2 for 5 days every 4 weeks) after a median of 21.5 days (12-34) from last pembro dose. Median duration on treatment with TMZ was 75 days (20-198) resulting in 1 complete response, 1 partial response, 6 PD and 2 not evaluable for response. Pts with response to TMZ had a higher median baseline lymphocyte count at the time of initiation of pembro (4131 vs. 1715 k/uL, p < 0.05) as well as TMZ (2335 vs. 965 k/uL, p = 0.08) as compared to pts without a response. Conclusions: TMZ is an interesting alternative for metastatic melanoma pts with disease progression on pembro. Our results show a 25% response rate. Further studies in this setting are warranted.

Abstract Abstract 942 Background: Early death in APL, most often due to bleeding, has emerged as the major cause of treatment failure now that curative strategies exist. Despite the routine use of ATRA, EDR remains high (Lehmann et al Leukemia 2011, Park et al Blood 2011). Although the optimal strategy to prevent early death is not clear, the recommendation is to initiate ATRA immediately at first suspicion of the disease without waiting for genetic confirmation. Therefore, we examined the timing of ATRA administration. Methods: To determine time interval from initial presentation to ATRA administration, we retrospectively collected data on all newly diagnosed APL pts presenting between 1992–2009 to 4 institutions: Northwestern University, Chicago, IL (university medical center); Memorial Sloan-Kettering Cancer Center, New York, NY (free standing cancer center); John J. Stroger Hospital of Cook County, Chicago, IL (public hospital); and Rambam Medical Center, Haifa, Israel, (Northern Israel's largest hospital; a tertiary referral center). We also examined 3 other time intervals: presentation to suspicion of APL, suspicion of APL to ordering ATRA, and ordering ATRA to its administration. Results: We identified 205 newly diagnosed APL pts: 46% men, median 48 years (range 1.5–85). Median white blood cell (WBC) count at presentation was 2,100/uL (range 300/uL-222,500/uL); 25% had high risk (HR) disease (WBC >10,000/uL). Median time interval from initial presentation to suspicion of APL was 1 day and median time from suspicion of APL to ordering ATRA was an additional day (table 1). ATRA was ordered on the day APL was suspected in 32% pts, the next day in 31%; 2 days after suspicion in 17%; and after 3 or more days in 16%. 89% received ATRA on the day ordered. At least 1 bleeding episode was identified in 34% of 185 pts with bleeding data available. Bleeding was associated with higher WBC count (p=0.0003) and lower hemoglobin (p=0.027) at presentation. 46 of 186 pts with complete information on time from presentation to administration of ATRA died. 23 (12%) died within 30 days of presentation; comprising half of all fatalities. Causes of death were: hemorrhage −15, sepsis −4, suspected MI −2, pneumonia −1, and sepsis plus differentiation syndrome -1. Among deaths within 30 days, 48%, 22%, 26% and 7% were in 1st through 4th weeks, respectively. 4 (18%) of these 23 pts died before ATRA was administered, all day 1 or 2 after presentation and all from bleeding. Only 15/182 pts received ATRA on day of presentation. Two of these 15 (13%) died within 30 days (none from bleeding). In comparison, 7/40 (18%) who received ATRA on day after presentation died within 30 days (71% from bleeding). 10/127 (8%) who received ATRA on day 2 or after died within 30 days (6 from bleeding). 20% in each group who received ATRA on either day of presentation or day 1 after presentation had HR disease. For this subgroup, if ATRA was administered on the day APL was suspected or one of the following 2 days, EDR was 19% (7/37). However, if ATRA was initiated on day 3 or 4, EDR was 80% (4/5); (p=0.013). 59% received ATRA prior to confirmation and 41% received ATRA on the day APL was confirmed or later. Conclusions: (1) APL was suspected rapidly upon presentation, usually within 1 day and ATRA was almost always administered on the day ordered. (2) However, ATRA was not given to most pts the day APL was suspected and for some 2 or more days elapsed. This time interval contributed to the delay in ATRA administration, suggesting physicians waited for marrow morphology or genetic confirmation before ordering ATRA. (3) Although at these centers a lower EDR (12%) than reported from the SEER database (17.3%) was observed, the current recommendation to give ATRA at first suspicion of APL was often not practiced. (4) There appears to be an association between EDR and timing of ATRA administration; other factors contribute to the EDR including variability in blood product support. (5) Our study argues that educating health care professionals who are the first to encounter APL pts as to the urgency of ATRA administration will reduce early deaths that occur even in the ATRA era. Disclosures: No relevant conflicts of interest to declare.

Introduction: JAK2 is located on chromosome 9p24 and includes 25 exons encoding a protein of about 1132 amino acids. JAK2 is one of the four Janus family non-receptor protein tyrosine kinases. JAK2V617F is by far the most prevalent mutation in BCR-ABL1-negative Myeloproliferative neoplasms (occurs in ∼95% of patients with polycythemia vera, in ∼55% with essential thrombocythemia and in ∼65% with primary myelofibrosis) 1, 2. More than 80% of hemochromatosis patients are homozygous for a C282Y mutation in HFE gene, and a smaller proportion are compound heterozygous for both the C282Y mutation and an H63D mutation3. Here we present the first case of an elderly female with concomitant diagnosis of Polycythemia Vera (PV) and hemochromatosis. To our knowledge, there is no literature about the co-existence or associations of these diseases. Case Reports: 75 year old female, former smoker with PMH of hemochromatosis and COPD with recent exacerbation, presented to the oncology clinic after hospital discharge for continuing care of her hemochromatosis requiring phlebotomy. She reports to have had multiple phlebotomies in the past fifteen years. Patient denied any history of liver disease, diabetes, arthralgia, skin pigmentation or sleep problems. Vital signs and examination were within normal limits. Her initial work up reported significantly elevated hemoglobin of 17.4gm/dl, hematocrit of 56.1%, RBC count of 6.98M/UL with MCV 80.4 fl, MCH 24.9 pg and platelet count of 673 K/UL. Peripheral smear showed normal red cell morphology and few giant platelets. Subsequently, further lab testing revealed ferritin of 25.7ng/ml. Her elevated hematocrit was further evaluated and erythropoietin was surprisingly <1mIU/ml. Genetic testing for HFE gene mutation screen was positive for homozygous C282Y mutation. Due to high suspicion for Polycythemia Vera, JAK2 mutation was also tested, which to our surprise, came back positive for JAK2 V617F point mutation. Patient is diagnosed with Polycythemia Vera and Hereditary Hemochromatosis and is recommended to start Aspirin, continue phlebotomy to maintain Hematocrit below 45% and take hydroxyurea for thrombocytosis. Discussion: It is interesting to note the co-existence of two un-related diseases. Franchini M et al analyzed 52 patients with PV for 12 HH gene mutations and found no significant association between the two conditions4. Hannuksela J et al studied C282Y and H63D mutations in 232 patients with hematological malignancies and reported no significant association5. Beaton and Adams in their review article about the myths and realities of hemochromatosis reports an elevated hemoglobin, in hemochromatosis's patient as a myth, based on their review of 634 C282Y homozygous patients at London health Science center, with mean hemoglobin of 145±13 g/L6. Our case re-iterates the importance of clinical suspicion of polycythemia Vera in a hemochromatosis patient with elevated hematocrit and undetectable erythropoietin. The coincidence is, phlebotomy is the treatment for both conditions as long as patient is fairly asymptomatic. References: 1. Ayalew Tefferi; Molecular drug targets in myeloproliferative neoplasms: mutant ABL1, JAK2, MPL, KIT, PDGFRA, PDGFRB and FGFR1; J Cell Mol Med. 2009 Feb; 13(2): 215-237. 2. Cross NC (2011); Genetic and epigenetic complexity in myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program 2011:208-214. 3. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet1996; 13:399-408. 4. Analysis of hemochromatosis gene mutations in 52 consecutive patients with polycythemia vera. Franchini M1, de Matteis G, Federici F, Solero P, Veneri D. Hematology. 2004 Oct-Dec;9(5-6):413-4. 5. Prevalence of HFE genotypes, C282Y and H63D, in patients with hematologic disorders. Hannuksela J, Savolainen ER, Koistinen P, Parkkila S. Haematologica. 2002 Feb;87(2):131-5. 6. The myths and realities of hemochromatosis Melanie D Beaton, Paul C Adams Can J Gastroenterol. 2007 February; 21(2): 101-104. PMCID: PMC2657669 Disclosures No relevant conflicts of interest to declare.

Abstract Background: Deletions in the Ikaros gene (IKZF1) have been associated with a poor outcome in pediatric B-ALL, but the interaction of IKZF1 deletions with other established prognostic factors, such as minimal residual disease (MRD), is still under investigation. Here we report the IKZF1 deletion status of 405 patients (pts) with acute lymphoblastic leukemia (ALL) and its association with other presenting features, end-induction MRD, and outcome. Methods: Between 2005-2011, 794 eligible pts (aged 1-18 yrs) with newly diagnosed pediatric ALL (B-ALL: 697; T-ALL: 97) were enrolled on DFCI ALL Consortium Protocol 05-001. End-induction MRD was assessed prospectively on all pts by allele-specific oligonucleotide-PCR assay. DNA was extracted from archived diagnostic blood or bone marrow samples from 399 B-ALL and 6 T-ALL pts with sufficient available material. Using a commercially available kit (SALSA MLPA P202 IKZF1, MRC-Holland), IKZF1 deletion status was assessed by multiplex ligation-dependent probe amplification (MLPA). Event free survival (EFS) and relapse free survival (RFS) were estimated using the method of Kaplan and Meier. Results: IKZF1 deletion was detected in 69 (17%) of the 405 evaluated pts. IKZF1 deletion was more common in pts over 10 years old (p<0.0001), males (p=0.05), Hispanic/Latinos (p=0.002) and those with presenting white blood cell count (WBC) at diagnosis ≥ 50K/ul (p<0.0001). IKZF1 deletions were detected in 7 of 13 (54%) pts with the Philadelphia chromosome (Ph+). Significantly more IKZF1 pts experienced induction failure (7% vs 1%, p=0.009) and relapse (25% vs 7%, p<0.0001) than pts without IKZF1 deletions. There was no difference in rates of treatment-related mortality. With a median follow-up of 5.3 years, the 5-year event free survival (EFS) for patients without IKZF1 deletion was 87% and 61% for those with IKZF1 deletion (p<0.0001; Figure 1). There was no significant difference in EFS based on type of IKZF1 deletion: 1) deletions of exons 4-7 or 4-8 (42% of cases, 5-yr EFS 51%) or 2) whole gene (49% of cases, 5-yr EFS 69%) (p=0.23). 315 Ph-negative B-ALL pts achieving complete remission (CR) had assessable end-induction MRD. Significantly more IKZF1 non-deleted pts had low MRD compared with IKZF1-deleted pts (95% vs 82%, p=0.006). For the 293 MRD-low pts, relapse occurred in 7% of IKZF1 non-deleted and 24% of IKZF1-deleted pts (p=0.004); for 22 MRD-high pts (all of whom received intensified therapy), there was no significant difference in relapse between IKZF1 non-deleted and IKZF1-deleted pts (21% vs 37%, p=0.62). The 5-yr relapse-free survival (RFS) was significantly worse for MRD-low pts with IKZF1 deletions versus those without these deletions (Figure 1). In multivariable analysis, IKZF1 status, but not MRD, was significantly associated with RFS for Ph-negative B-ALL pts. (Table 1) Conclusions: IKZF1 deletion is associated with higher rates of induction failure and relapse, and is a significant predictor of inferior outcome in pediatric B-ALL. IKZF1 deletion was associated with significantly higher rates of relapse in Ph-negative B-ALL patients with low end-induction MRD, and thus may be useful factor to consider when stratifying treatment intensity in this subset of pts. We conclude that IKZF1 deletion should be incorporated into risk stratification for pediatric B-ALL. Table 1. Prognostic Factors for RFS for B-ALL, Ph-negative pts with evaluable end-induction MRD Univariate Multivariable HR [95% CI] p-value HR [95% CI] p-value Age, ≥10 vs <10 1.40 [0.68-2.91] 0.36 1.19 [0.56-2.51] 0.65 IKZF1, del vs. not 3.23 [1.61-6.45] 0.0009 2.53 [1.20-5.30] 0.01 MRD, high vs. low 2.51 [1.04-6.03] 0.04 1.63 [0.64-4.11] 0.30 WBC, ≥50 vs. <50 2.50 [1.27-4.94] 0.008 1.99 [0.98-4.03] 0.06 [HR=Hazard ratio] Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 1789 INTRODUCTION: Ibrutinib (PCI 32765) is an orally administered covalent inhibitor of Bruton's Tyrosine Kinase (BTK). Ibrutinib has significant activity in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and is typically well tolerated (Byrd ASCO 2011, O'Brien ASH 2011). Rarely serious bleeding in patients concurrently on oral anticoagulation has been reported but was not related to thrombocytopenia (O'Brien ASH 2011). However, grade 1 or 2 ecchymosis/contusion is a frequent adverse event in patients on ibrutinib. In addition to being essential for B cell receptor signaling BTK is also involved in the signaling of the glycoprotein (GP)VI and GPIV von Willebrand (vW) receptors (Liu, Blood 2006). Thus, it is possible that ibrutinib could increase the bleeding risk by interfering with thrombus formation. In addition, lymphoproliferative disorders and some drugs have been associated with acquired vW-disease (AvWD). METHODS AND PATIENTS: In an ongoing single center, open label phase II trial we treat CLL/SLL patients with ibrutinib 420 mg daily on 28 day cycles (NCT01500733). We measured platelet (PLT) function on the PFA-100 instrument, vW-factor (vWF) antigen levels and activity (vWF-Ag/vWF-Act), and factor VIII (FVIII) on baseline, days 2 and 28. Here we report on effects of ibrutinib on platelet counts and function in 25 patients who completed >2 cycles. RESULTS: PLT counts prior to treatment ranged from 36 k/μl to 256 k/μl with a median of 102 k/μl. Twelve (48%) patients had a pre-treatment PLT count <100 k/μl. Median PLT counts for days 14, 28, and 56 increased to 140, 137, and 135 k/μl, respectively (P<.01). 76% of patients showed an increase after only 2 weeks on drug (median increase 25 k/μl (range 4–183 k/μl) that was sustained at subsequent timepoints. On day 14, 6 patients (24%) had a decrease in PLT count by a median of 13 k/μl from baseline; of these, 3 had a pre-treatment PLT count of <100 k/ul and 1 developed grade III thrombocytopenia (42 k/μl) that resolved to >100 k/μl by day 56. 20% (5 of 25) of patients reported grade 1 spontaneous ecchymosis with no correlation to platelet count, PFA testing, or vWF measurements. Of note we performed lymph node core biopsies in 35 patients taking ibrutinib with minimal bruising. Only 2 patients had more extensive local bruising/ecchymosis at the biopsy site. In 19 patients PFA-100 measurements of epinephrine (EPI) and adenosine diphosphate (ADP) stimulated platelet aggregation times were available (test requires PLT count >100 k/μl). Median changes in closure times with EPI and ADP on treatment were not significantly different from baseline (See table). Four (21%) patients started with abnormally prolonged EPI closure times (one on aspirin, one on ibuprofen; discontinued with the start of ibrutinib) which resolved by day 28 in 3 and decreased in 1. Three (16%) patients had a prolongation of EPI closure times on day 2 that resolved by day 28 in 2 and decreased in 1. All closure times on ADP were low or normal. No patients with abnormal PFA testing demonstrated spontaneous ecchymosis. From baseline to day 28 vWF-Act, vWF-Ag and FVIII decreased (P<0.05; n=24). All 3 values were high normal to elevated prior to treatment and decreased to normal on treatment. CONCLUSION: This preliminary report does not identify any significant ibrutinib effect on platelet function. PLT counts improved rapidly in the majority of patients and when seen transient decreases have been minimal. Three patients (16%) developed an abnormal reading in PLT function tests on treatment but none developed spontaneous echymosis or bleeding. The observed normalization of mildly elevated baseline levels of vWF and FVIII seems most consistent with a reduction in acute phase reactants and there was no evidence for AvWD on ibrutinib. The apparent functional tolerance of BTK inhibition in platelets is likely attributable to redundancy in the affected signaling pathways. This work was supported by the Intramural Research Program of NHLBI, NIH. We thank our patients for participating in these research studies. Disclosures: No relevant conflicts of interest to declare.