Median White Blood Cell Count Research Articles

Characteristics and Role of Lenalidomide Therapy in Patients with Myelodysplastic/Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis

Introduction:Myelodysplastic/Myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), previously known as RARS-T is now recognized as a full entity in the 2016 World Health Organization classification of myeloid neoplasms and acute leukemia. It is characterized by thrombocytosis (>=450 x 109/L), refractory anemia, with dyserythropoiesis in the bone marrow with >=15% ringed sideroblasts, and megakaryocytes with features resembling those in myelofibrosis or essential thrombocythemia. Currently there are no formal guidelines for the management of this disease. Lenalidomide has been described in case reports to have clinical activity in this rare disorder. Here we describe the disease characteristics and efficacy of lenalidomide in patients with MDS/MPN-RS-T.Methods:We reviewed the records of 53 patients with MDS/MPN-RS-T that presented to MD Anderson Cancer Center since 2000. Of these, we identified 7 patients that were confirmed to have MDS/MPN-RS-T and were treated with lenalidomide. In addition to the demographic data, we also collected information on cytogenetics, the international prognostic scoring system (IPSS) and the mutational status including JAK2, MPL, CALR and SF3B1. We also collected data on thrombosis and cardiovascular risk factors.Results:Seven patients were noted to have MDS/MPN-RS-T, of which 4 were male and 6 were white. All 7 patients were categorized as lower risk MDS by the IPSS (4 had low risk disease, 3 had intermediate 1). Five of the 7 patients had a diploid karyotype while 1 patient had del 11q and 1 had inversion 3q21. Median platelet count was 713 x 109/L (range 462-993), median hemoglobin was 10 gm/dl (range 8.3-11.3) and median white blood cell count was 9.7 x 109/L (range 4.5-24). Five of the seven patients (71%) harbored a JAK2V617F mutation, 1 harbored MPL. Only 2 patients were noted to have a SF3B1 mutation while testing was not available for the remaining 5 patients. Three patients that had CALR testing done were all negative for the mutation. Two patients were noted to carry an ASXL1 mutation. Two patients had coronary artery disease prior to being diagnosed with MDS/MPN-RS-T. Of these 1 patient also had pulmonary embolism prior to being diagnosed, while the other patient had deep vein thrombosis after diagnosis. Median time from diagnosis to treatment was 12.4 months (range 2.1-47.4). Median number of prior therapies was 1 (range 0-3). Three patients received lenalidomide frontline therapy. Overall, 3/7 patients (43%) responded to lenalidomide therapy. Four patients were red cell transfusion dependent at the time of lenalidomide initiation. Of these half became transfusion independent. Of the 3 patients that were transfusion independent at lenalidomide initiation, 1 responded with improvement in counts, 1 showed no hematological improvement, while 1 patient stopped therapy after 2 cycles due to rash. Of the patients with no hematological improvement to lenalidomide, all 3 patients had overall stable disease and good tolerance to therapy. Only 1 patient achieved molecular remission. None of the 2 patients carrying the ASXL1 mutation, and patient with inversion 3q21 responded to lenalidomide therapy. Median time on lenalidomide therapy was 14 months (3-30). Only 1 patient has died while none of the patients transformed to acute leukemia. Median overall survival has not been reached.Conclusion:MDS/MPN-RS-T, a recently approved WHO entity, has no consensus on optimal treatment and response criteria. Lenalidomide in our study shows clinical activity with improvement in counts and achieving transfusion independence. Also noted is stabilization of counts in those who fail to achieve a hematological improvement. We need to further explore its role in MDS/MPN-RS-T in larger clinical trials. DisclosuresSasaki:Otsuka Pharmaceutical: Honoraria.

Final Report of a Phase II Study of Guadecitabine (SGI-110) in Patients (pts) with Previously Untreated Myelodysplastic Syndrome (MDS)

Introduction: The hypomethylating agents (HMA) are the standard of care for a majority of patients with higher-risk MDS. SGI-110 is a second generation HMA that molecularly is a dinucleotide derivative of decitabine and therefore a more potent inhibitor of DNA methyltransferase activity. SGI-110 is currently being studied in front-line AML and second-line MDS multicenter studies. Here we present results of a single arm phase II trial of SGI-110 for patients with previously untreated MDS.Methods: Patients, age 18 or older, with adequate renal and hepatic functions, with int-2 or high risk MDS by IPSS or more than 10% blasts in bone marrow were eligible. One prior cycle of azacitidine or decitabine was allowed. No prior other therapies were allowed. SGI-110 was administered at a dose of 60 mg/m2 SC daily x 5 days every 4 weeks. The study was designed with stopping rules for response, toxicity, and mortality (first 3 months). A maximum of 100 patients could be treated.Results: From 11/14/2014 to 7/31/2018, 94 patients have been treated. Median age was 69 years (22.7-91.9), 72 patients (77%) had INT-2, 13 patients (14%) high risk. Median % of marrow blasts was 10 (range, 0-20). Median white blood cell count and platelet count were 2.5 (×106/L), and 52 (×106/L) respectively. Twenty two patients (23%) were diploid, 36 (38%) complex, and 33 (35%) others. Mutation distribution was as follows: TP53, 29 (31%); ASXL1, 26 (28%); TET2, 20 (21%); RUNX1, 19 (20%); RAS, 12 (13%); DNMT3A, 10 (11%); EZH2, 9 (10%); SRSF2, 6 (7%); PHF6, 4 (4%); BCOR, 3 (3%); CEBPA, 3 (3%); SF3B1, 3 (3%); IDH2, 3 (3%); BRAF, 2 (2%); CBL 2 (2%); MPL, 2 (2%); NPM1, 2 (2%); U2AF1, 2 (2%); WT1, 2 (2%); CREBBP, 1 (1%); ETV6, 1 (1%); FLT3-ITD, 1 (1%); GATA2, 1 (1%); IDH1, 1 (1%); SETBP1, 1 (1%); ZRSR2, 1 (1%). The median number of cycles received was 5 (range 1 - 32). Ninety four (100 %) patients are evaluable for toxicity. Early mortality was 0%. Common toxicities were fatigue (61%), infection (46%), nausea (27%), pain (19%), and constipation (16%), mucositis (16%), dyspnea (15%), local injection toxicity (15%), and diarrhea (12%). Eighty seven (93%) patients were evaluable for response. The median number of cycles to response was 3 (range 1 - 11). Overall response rate was 53 (61%); CR 19 (22%), CRp 3 (3%), HI 31 (36%), SD 5 (6%), NR 27 (31%), and died 2 (2%). With a median follow-up of 15 months, the median OS was 15 months and the median EFS was 14 months (Figure 1). By UVA, higher ACE-27 score showed tendency of lower rates of response (p=0.063; hazard ratio [HR], 1.383; 95% confidence interval [CI], 0.982-1946). However, MVA did not show any prognostic factors for response. By MVA characteristics associated with survival were: complex karyotype (p=0.036; HR, 2.345; 95% CI, 1.055-5.210), and response to therapy (p=0.003; HR, 0.272; 95% CI, 0.114-0.648).In conclusion: SGI-110 is well tolerated in previously untreated MDS. ORR appears to be better than expected compared to azacitidine or decitabine. Longer follow-up and randomized trials will be needed to understand effect on survival. [Display omitted] DisclosuresSasaki:Otsuka Pharmaceutical: Honoraria. Bose:Incyte Corporation: Honoraria, Research Funding; CTI BioPharma: Research Funding; Celgene Corporation: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Blueprint Medicines Corporation: Research Funding; Pfizer, Inc.: Research Funding. Daver:Pfizer: Consultancy; Karyopharm: Research Funding; Novartis: Consultancy; Daiichi-Sankyo: Research Funding; Karyopharm: Consultancy; ARIAD: Research Funding; Novartis: Research Funding; Incyte: Research Funding; Incyte: Consultancy; BMS: Research Funding; Otsuka: Consultancy; Alexion: Consultancy; Sunesis: Consultancy; Pfizer: Research Funding; Sunesis: Research Funding; ImmunoGen: Consultancy; Kiromic: Research Funding. Ravandi:Bristol-Myers Squibb: Research Funding; Sunesis: Honoraria; Orsenix: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Astellas Pharmaceuticals: Consultancy, Honoraria; Xencor: Research Funding; Seattle Genetics: Research Funding; Abbvie: Research Funding; Orsenix: Honoraria; Astellas Pharmaceuticals: Consultancy, Honoraria; Bristol-Myers Squibb: Research Funding; Jazz: Honoraria; Seattle Genetics: Research Funding; Abbvie: Research Funding; Jazz: Honoraria; Sunesis: Honoraria; Amgen: Honoraria, Research Funding, Speakers Bureau; Macrogenix: Honoraria, Research Funding; Macrogenix: Honoraria, Research Funding; Xencor: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Arog: Research Funding. DiNardo:Celgene: Honoraria; Agios: Consultancy; Karyopharm: Honoraria; Abbvie: Honoraria; Bayer: Honoraria; Medimmune: Honoraria. Pemmaraju:SagerStrong Foundation: Research Funding; Affymetrix: Research Funding; plexxikon: Research Funding; daiichi sankyo: Research Funding; samus: Research Funding; celgene: Consultancy, Honoraria; abbvie: Research Funding; cellectis: Research Funding; stemline: Consultancy, Honoraria, Research Funding; novartis: Research Funding. Kadia:Novartis: Consultancy; Amgen: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Pfizer: Consultancy, Research Funding; BMS: Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Celgene: Research Funding; BMS: Research Funding; Celgene: Research Funding; Novartis: Consultancy; Jazz: Consultancy, Research Funding; Abbvie: Consultancy; Takeda: Consultancy; Takeda: Consultancy.

Ratify (Alliance 10603): Prognostic Impact of FLT3 tyrosine Kinase Domain (TKD) and NPM1 Mutation Status in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Midostaurin or Placebo Plus Standard Chemotherapy

Ratify (Alliance 10603): Prognostic Impact of FLT3 tyrosine Kinase Domain (TKD) and NPM1 Mutation Status in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Midostaurin or Placebo Plus Standard Chemotherapy

Clinical Significance of Occult Central Nervous System Disease in Adult ACUTE Lymphoblastic Leukemia. a Multicenter,Report from the Campus ALL/Gimema Network

Introduction. In a modern context of improved management of acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement at diagnosis remains an obstacle towards long-term cure. We have previously reported that flow cytometry (FCM) is better than conventional cytology (CC) in demonstrating the presence of leukemic cells in patients' (pts) cerebrospinal fluid (CSF), especially in samples with low cell counts. In the framework of the national Campus ALL program aimed at improving the management of adult ALL patients enrolled in the GIMEMA protocols, we retrospectively evaluated the incidence of occult CNS positivity and its impact on outcome in 221 adult pts with newly diagnosed ALL from 11 centers.Methods. Ninety-four patients (42%) were females and 127 (58%) males, with a median age of 44 years (range 17-80), a median white blood cell (WBC) count of 10.6x109/L (range 0.1-457). One hundred and seventy pts (77%) had B-lineage ALL. Cytogenetic/genetic data were available in 167 (75%) pts: 58 (35%) had a BCR/ABL rearrangement, 14 (8%) a complex karyotype and 11 (6%) a MLL rearrangement. Pts were treated according to the GIMEMA/NILG ALL protocols or with the Hyper-CVAD program. Ninety-eight pts underwent an allogeneic stem cell transplant (ASCT). Median follow up was 26.8 months (range 1-136.6). All CSF samples were evaluated both by CC and FCM. The presence of ≥10 clonally restricted or phenotypically abnormal events was regarded as a FCM positivity. Based on the results of CSF examination, three different categories were recognized: manifest CNS+ (CC+FCM+), occult CNS+ (CC-FCM+) and CNS- (CC-FCM-).Results. Overall, 16 (7%) pts had manifest CNS+, 39 (17%) occult CNS+ and 166 (75%) were CNS-Median age, WBC count, B/T lineage, cytogenetic/genetic features did not differ significantly between the three categories. A complete remission (CR) was achieved in 178 (80%) pts, 9 (4%) died early in induction and 104/178 (58%) experienced a relapse. The frequency of CR rate did not vary significantly across the three identified categories. In univariate analysis, the CNS status correlated significantly with the incidence of relapse (p=.004) and with censor (<.00002). The four-year overall survival (OS) for manifest CNS+, occult CNS+ and CNS- pts was 6%, 17% and 46%, respectively (p=.0007) (Figure). No difference in terms of OS was observed between manifestand occult CNS+ pts (p=.30). In multivariate analysis a baseline status of manifestor occult CNS+ (RR: 1.98, 95%CI 1.47-2.43, p=0.00001) and age>45 years (RR:1.45, 95% CI 1.47-2.43, p=0.04)were independently associated with a lower OS.Conclusions. Our large, multicenter CAMPUS ALL study showed that i) in ALL adult pts, FCM allows to detect occult CNS disease, even in conditions of low spinal fluid leukemic count; ii) the presence of occult CNS disease is associated with an unfavorable outcome. Further prospective studies on larger series are needed to confirm these data. DisclosuresDel Principe:Gilead: Membership on an entity's Board of Directors or advisory committees. Fracchiolla:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Foà:NOVARTIS: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau.

ATG2B/Gskip in De Novo Acute Myeloid Leukemia (AML): High Prevalence of Germline Predisposition in French West Indies and Potential Role of Overexpression in Acquired AML

In 2015, a germline copy number variation of chromosome 14 (CNVdup14) including ATG2B and GSKIP genes was described as a predisposition genetic factor responsible of familial myeloproliferative neoplasms from French West Indies (Saliba et al, Nat Gen 2015), frequently progressing to AML. In this study, we looked at the presence of this CNVdup14 in a cohort of Caribbean islands patients (pts) with non-secondary aggressive hematological malignancies (HM). We also studied the expression of ATG2B and GSKIP genes in a cohort of acquired AML pts.This is a retrospective multicenter study of adults Caribbean islands pts treated at Gustave Roussy Cancer Center (Villejuif, France) and at the French West Indian hospitals (Martinique and Guadeloupe) between May 2000 and May 2018. We included pts with AML, acute undifferentiated leukemia (AUL), acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Pts with personal history of myeloproliferative or myelodysplastic syndromes before the onset of aggressive HM were not included in this study. The presence of the CNVdup14 was carried out by PCR analyses in all the pts.For the second part of the study, expression of ATG2B and GSKIP genes were assessed in newly diagnosed de novo AML pts with normal karyotype or trisomy 8 (samples from the GOELAMSTHEQUE) by quantitative RT-PCR and expressed as relative expression PPIA/HPRT/H2A.Z.One hundred pts were analyzed. Median age was 52 years (IQ 40-62) with male predominance (61%). Fifty eight pts came from Martinique, 42 pts from the rest of the Caribbean islands (including 28, 4, 3, 2 pts from Guadeloupe, Haiti, Saint Martin, Dominican Republic, respectively). Seventy eight pts had AML. Among them, according to revised MRC cytogenetic classification, 11 (14%) were favorable, 47 (60%) intermediate and 20 (26%) adverse. Seventeen pts had ALL, 3 LL, and 2 AUL. On the entire cohort, all except nine pts were treated with intensive chemotherapy, 80 reached complete remission, 29 relapsed, 46 pts died. Thirty two pts received hematopoietic stem cell transplantation (HSCT).Six pts were positive for the CNVdup14 by PCR (confirmed by SNP array in the 5 pts with leftover DNA available). All had an AML (no pts with favorable AML) and were originated from Martinique. These pts represented 14% of the 43 AML from Martinique in our cohort (17% if we excluded favorable AML). One was known to be part of an ATG2B/GSKIP family, 2 pts had no familial history of myeloid malignancies and 2 new families were discovered. Median white blood cell, hemoglobin and platelets counts were 17.7 G/l (IQ 6.7-48), 8.15 g/dl (6.9-9.7) and 58 G/l (20-132), respectively. Median age at AML diagnosis was 49 years (34-55), 3/6 (50%) had extramedullary localization compared to 11/78 (14%) for others AML pts. Karyotype was normal for 4, or showed a monosomy 7 for 2 pts. NGS panel showed distinct abnormalities compared to the entire cohort (Fig A). None had JAK2, MPL, CALR, P53, RUNX1, DNMT3A, FLT3-ITD mutations. All harbored an epigenetic and/or spliceosome mutation (IDH n=3, TET2 n=3, ASLX1 n=3, SRSF2 n=3). Five out of the six pts received intensive treatment and 4 achieved complete remission. Two received HSCT, 2 relapsed and 4 died.Median overall survival (OS) of the entire cohort was 35.7 months (22.5-89.5) and progression free survival (PFS) 27.6 months (15.6 -56.1). As CNVdup14 pts had AML only, we next evaluated survival according to the predisposition status in the AML cohort. Pts with CNVdup14 had a median OS and PFS of 19 (6.5-29) and 11.4 (6.5-29) months, respectively, compared with 52.6 (22.9-100.2) and 30 months (15.6-60) in CNV wild-type counterparts (PFS Fig B).We next evaluated ATG2B and GSKIP expression in a cohort of 46 random de novo AML pts (GOELAMS-LAM-IR-2006 multicenter trial). Median expression of ATG2B and GSKIP were 4.8 (2.6-12.9) and 5.3 (0.3-5.1) respectively. No CNVdup14 was detected. Interestingly we found a correlation between the two genes expression (Pearson Correlation Coefficients 0.55 and linear regression p< 0.001, Fig C). Expression of ATG2B and GSKIP was also correlated with leukocytosis (p=0.003 and p=0.07) (Fig D). We found no impact on OS and PFS.For the first time, we described a high percentage of the germline CNVdup14 in de novo AML pts from Martinique (14%). Moreover evaluation of ATG2B and GSKIP expression suggested that the role of theses 2 genes in leukemogenesis is not limited to pts with the CNVdup14. [Display omitted] Disclosuresde Botton:Agios: Research Funding; Celgene: Honoraria, Research Funding. Benabelali:CERBA laboratory: Employment.

Characteristics and Outcome of Older Patients with Acute Promyelocytic Leukemia Front-Line Treated with or without Arsenic Trioxide — an International Collaborative Study

Background: Characteristics and outcome of older patients (pts) with acute promyelocytic leukemia (APL) are unclear due to lack of clinical data.Aims: To describe a large series of older APL pts and compare outcome according to treatment strategy.Methods: We retrospectively studied 475 APL pts (median age, 73.8 yrs; range, 70-90.3 yrs), treated between 1990 and 2018 within four study groups/institutions of the US and Europe (Acute Leukemia French Association, n=228; Programa Espanol de Tratamientos en Hematologia, n=211; Study Alliance Leukemia, n=28; Johns Hopkins School of Medicine, Baltimore, n=8). APL was confirmed either by cytogenetics, fluorescence in situ hybridization and/or polymerase chain reaction. For analysis, pts were grouped according to treatment: i) chemotherapy/all-trans retinoic acid (CTX/ATRA, n=260; consisting of daunorubicin/idarubicin and ATRA for induction and different CTXs+ATRA for consolidation), ii) ATO/ATRA±CTX, n=177 (according to Lo-Coco F, et al. NEJM, 2013, n=23 or CTX/ATO/ATRA, n=154), iii) less intensive therapy, n=26 (reduced CTX, n=2 or ATRA only, n=24) and iv) no treatment/unknown, n=12.Results: Median white blood cell (WBC) and platelet counts at diagnosis were 1.5/nl (range, 0.1-242/nl) and 37/nl (range, 2-261/nl), respectively. Two-hundred twenty-nine pts (48%) were female. Cytogenetic analysis was available in 408 pts and 85 (21%) had additional abnormalities. BCR3 was positive in 138 (44%) of 316 available pts. Only 15 (22%) of 69 tested pts were FLT3-ITD positive. One hundred (22%) of 464 pts had a WBC count >10/nl. Median WBC was significantly lower (P<0.001) in the ATO/ATRA±CTX group (1.2/nl) as compared to the CTX/ATRA (2.05/nl) or less intensive (2.8/nl) group. Median age was comparable in CTX/ATRA (73.5 yrs) and ATO/ATRA±CTX (73.6 yrs) but significantly higher (P<0.001) in the less intensive group (79.6 yrs). Median platelet counts were comparable (P=0.08) in the three groups (CTX/ATRA, 34.5/nl; ATO/ATRA±CTX, 41/nl; less intensive, 39/nl). Response data were available in 459 (97%) pts.Complete remission (CR) after induction therapy was achieved in 75% (194/259) of the CTX/ATRA group, in 93% (162/174) of the ATO/ATRA±CTX group, and in 50% (13/26) of the less intensive group. Two pts of the CTX/ATRA group and one patient after ATRA only were refractory. Early death rates were 24% (n=63) after CTX/ATRA, 7% (n=12) after ATO/ATRA±CTX and 46% (n=12) in the less intensive group. A logistic regression model revealed age above 75 yrs (odds ratio [OR], 0.53; P=0.02) higher WBC (OR, 0.35; P<0.001), less intensive treatment (OR, 0.46; P=0.08) and therapy with ATO/ATRA±CTX (OR, 4.2; P<0.001) as significant factors for achievement of a CR. Median follow-up was 4.7 yrs (95%-CI, 4.2-5.4 yrs) and 5-yrs overall survival (OS) 62% (95%-CI, 57-67%). Treatment with ATO/ATRA±CTX was associated with significantly higher 5-yrs relapse-free (RFS; 96% [95%-CI, 92-99%] vs. 88% [95%-CI, 83-93%]; P=0.007) and OS rates (78% [95%-CI, 72-85] vs. 58% [95%-CI, 52-65%]; P<0.001) as compared to CTX/ATRA. Of note, higher WBC count (>10/nl) was associated with an inferior RFS in CTX/ATRA (P<0.001), but not in ATO/ATRA±CTX (P=0.47). When restricting the analysis according to treatment period after the year 2000, ATO/ATRA±CTX was still associated with a significant better RFS (P=0.05) and OS (P<0.001) as compared to CTX/ATRA. Overall, only five pts relapsed after ATO/ATRA±CTX as compared to 33 after CTX/ATRA. As expected, higher WBC (>10/nl; hazard ratio [HR], 2.36; P<0.001), age >75 yrs (HR, 2.07; P<0.001) and therapy with ATO/ATRA±CTX (HR, 0.48; P<0.001) were significant factors for OS.Conclusions: The ATO-based regimen for first line treatment of elderly APL pts was associated with excellent and sustained response rates. Our data demonstrate the important potential of ATO/ATRA in the primary management of older APL pts. DisclosuresFenaux:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding. Schlenk:Pfizer: Research Funding, Speakers Bureau. Platzbecker:Celgene: Research Funding. Montesinos:Novartis: Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Speakers Bureau.

Weight Increase during Induction Therapy Predicts Intensive Care Unit (ICU) Transfer in Patients (Pts) with Acute Promyelocytic Leukemia (APL)

Weight Increase during Induction Therapy Predicts Intensive Care Unit (ICU) Transfer in Patients (Pts) with Acute Promyelocytic Leukemia (APL)

Efficacy and Safety of Hydroxyurea in the Treatment of Sickle Cell Anemia Children in Jos, North Central Nigeria

Introduction: Sickle Cell Anaemia (SCA) is a genetic disorder with significant morbidity and mortality, and Nigeria accounts for the highest burden of the disease worldwide. Hydroxyurea has been shown to positively modify the disease pathogenesis, but its use is low among Nigerian SCA patients because of efficacy and safety concerns. Hence, this study evaluated the efficacy, tolerability and safety of hydroxyurea in Nigerian children with SCA.Methods: A Quasi-experimental study with a before and after design using hydroxyurea as the intervention in 54 SCA children aged 4-17years, who have had at least two or more painful vaso-occlusive events requiring parenteral analgesia in the previous 12 months.The number of Vaso-Occlusive Crisis (VOC), Acute Chest Syndrome (ACS), blood transfusions and hospitalisations in the previous 12 months obtained from the subjects' hospital records; and percentage fetal haemoglobin, Packed Cell Volume (PCV), White Blood Cell Counts (WBC) and Platelet Counts at baseline and after 12 months of hydroxyurea therapy were compared.The research participants were observed clinically for tolerability and adverse events of hydroxyurea while haematologic toxicity of hydroxyurea was monitored using complete blood count at specified intervals.Wilcoxon Signed-Rank Test was used to compare the differences in the median values of the clinical and haematologic parameters at baseline and after 12 months of hydroxyurea therapy and a p-value of < 0.05 was considered statistically significant.Results: The number of VOCs and hospitalisations reduced from the median baseline values of 3(2-3) and 2(2-3) respectively to 0(0), (p <0.0001). Blood transfusions as well as ACS declined from 48.1% and 11.2% at baseline to 5.6% and 0.0% respectively (p <0.05). The median PCV increased from 26.0(22.0-27.0) % to 28.0(25.8-30.2) % (p <0.0001) while the median WBC reduced from 11.1(7.3-14.6) x 109/L to 6.2(4.8-10.4) x 109/L (p < 0.0001) and the median platelet counts reduced from 411(264-496) x 109/L to 347(251-402) x 109/L (p= 0.009). A dose-dependent and reversible leucopenia was observed among six children (11.1%), otherwise, hydroxyurea was safe and well tolerated in the study population.Conclusion: These findings suggest that hydroxyurea is efficacious, tolerable and safe in SCA children in Jos, Nigeria. The findings could serve as part of an educational template that could help improve the level of utilisation of hydroxyurea among sickle cell anaemia children in Jos, Nigeria. DisclosuresNo relevant conflicts of interest to declare.

NPM1 mutated AML can relapse with wild-type NPM1: persistent clonal hematopoiesis can drive relapse

AbstractAcute myeloid leukemia (AML) with NPM1 mutation (NPM1mut) defines a World Health Organization entity. Absence of minimal residual disease (MRD) following induction chemotherapy is associated with an excellent prognosis. Data are conflicting on NPM1mut AML relapsing with wild-type NPM1 (NPM1wt). We analyzed 104 paired samples of NPM1mut AML patients with relapse and identified 14/104 that relapsed with NPM1wt AML. Blood counts at diagnosis differed significantly between patients with NPM1mut and NPM1wt relapse (median white blood cell count, 30 vs 3 × 109/L, P = .008; platelet count, 66 vs 128 × 109/l, P = .018). NPM1mut relapse occurred significantly earlier than NPM1wt relapse (14 vs 43 months, P = .004). At diagnosis, FLT3-ITD were more frequent in patients with NPM1mut relapse (P = .029), whereas DNMT3A mutations were more frequent in patients with NPM1wt relapse (P = .035). Sequencing analysis of paired samples at diagnosis, molecular remission, and NPM1wt relapse identified cooccurring mutations that persist from diagnosis throughout remission and at relapse, suggestive of a preexisting clonal hematopoiesis. We provide evidence that AML relapsing with NPM1wt is a distinct disease and that initial leukemia and relapse potentially arise from a premalignant clonal hematopoiesis.

1988. Development of a Laboratory Stewardship Algorithm for Anaplasma phagocytophilum Polymerase Chain Reaction Testing

BackgroundAnaplasmosis often presents with fever and headache, and typical laboratory abnormalities include leukopenia and thrombocytopenia. Polymerase chain reaction (PCR) is the preferred diagnostic method. At our institution, Anaplasma PCR is overutilized, with a low positivity rate. To improve utilization, we performed a two-part study. Part 1 determined if complete blood count (CBC) values could exclude Anaplasma infection. A stewardship algorithm was implemented during part 2 of the study via a mock stewardship protocol.MethodsPart 1: Anaplasma PCR tests were included over a 3-year period. For each PCR result, white blood cell (WBC) and platelet (PLT) results from a sample collected near the time of PCR were evaluated in R Studio and GraphPad Prism. The significance of differences between PCR-positive and -negative cases was determined using the Mann–Whitney test. Cut-off values were chosen to maximize sensitivity of a screening algorithm for the detection of Anaplasma infection. Part 2: Mock stewardship was performed for 6 months. Screening criteria generated in phase 1 were applied to determine whether Anaplasma PCR would have been approved or rejected if stewardship were implemented based on laboratory and clinical parameters.ResultsPart 1: 2166 PCR tests were included. Patients with a positive Anaplasma PCR had lower median WBC and PLT counts than those with a negative result (Figure 1). Combining criteria of a WBC ≥11 K/µL and PLT ≥300 K/µL provided rejection criteria with 100% sensitivity and 25% specificity after excluding immunocompromised or unstable patients (Figure 2). Part 2: 663 PCR tests were analyzed. Of those, 155 (23%) met CBC rejection criteria and were reviewed by committee. The committee mock refused 110 (71%) tests and mock accepted 49 (29%) based on clinical criteria. Of the patients with positive Anaplasma PCR, 1 met CBC rejection criteria and was mock refused by committee. On review, the patient was completing treatment for Anaplasmosis, indicating limited utility of testing. None of the 45 samples that were mock accepted by clinical criteria was positive by PCR, demonstrating no additional benefit of chart review. ConclusionImplementation of a CBC-based stewardship algorithm would reduce unnecessary Anaplasma PCR testing and decrease cost by 23%.Disclosures J. Baron, Roche Diagnostics: Possible Consulting Role—not finalized at this point, No compensation yet—compensation TBD

488. Oral Vancomycin Plus Intravenous Metronidazole for Severe Clostridium difficile Infection in Critically Ill Patients

BackgroundThere remains a paucity of data regarding optimal treatment of patients with severe Clostridium difficile infection (CDI) in the intensive care unit (ICU). Based on expert opinion, the 2018 SHEA-IDSA CDI Clinical Practice Guidelines recommend combination therapy (oral vancomycin [PO VAN] plus intravenous metronidazole [IV MDZ]) in fulminant CDI only. A 2015 study suggested a mortality benefit with combination therapy of PO VAN plus IV MDZ for ICU patients regardless of severity. The objective of this study was to determine the impact of combination therapy on clinical outcomes in ICU patients with severe CDI, compared with PO VAN monotherapy.MethodsSingle-center, retrospective, cohort of adult patients admitted to an ICU between April 2016 and April 2018 with a positive C. difficile nucleic acid amplification test and an order for PO VAN were screened for inclusion. Patients were excluded if they had life-threatening intra-abdominal complications, including toxic megacolon/emergent colectomy. The primary outcome was 30-day in-hospital all-cause mortality. In a subgroup analysis, patients were matched using Acute Physiology and Chronic Health Evaluation (APACHE) II scores. Logistic regression was conducted to identify clinical variables associated with mortality.ResultsOne hundred one patients were included; 47 received combination therapy with IV MDZ. Baseline characteristics were similar across groups, except patients in the IV MDZ group had a higher median white blood cell (WBC) count at diagnosis (18.4 vs. 13.9, P = 0.023) and were more likely to receive a higher dose (500 mg) of PO VAN (36.2% vs. 7.4%, P < 0.0001). Thirty-day mortality was 14.9% in the combination group vs. 7.4% in the monotherapy group, (P = 0.338). APACHE II Score was the only variable independently associated with 30-day mortality (OR = 1.13, 95% CI 1.03 – 1.24). There was no difference in probability of receiving IV MDZ based on APACHE II score. In a subgroup of patients matched by APACHE II score (n = 76), mortality remained nonsignificantly different (15.8% vs. 9.7%, P = 0.480).ConclusionOur data question the utility of IV MDZ in addition to PO VAN for ICU patients with severe CDI. There remains a possibility for confounding by indication in this retrospective analysis.Disclosures E. Heil, ALK-Abelló: Grant Investigator, Research grant. K. Claeys, Nabriva: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee.

Clinical analysis on granulocyte colony stimulating factor mobilized allogenetic peripheral blood mononuclear cell transfusion for one patient with primary myelofibrosis in fibrosis stage

Objective To investigate the safety and efficacy of granulocyte colony stimulating factor mobilized allogenetic peripheral blood mononuclear cell (G-PBMNC) in treatment of patient with primary myelofibrosis (PMF) in fibrosis stage with high risk and unsuitable for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods In March 2016, a case of male PMF patient (age: 70 years old)in fibrosis stage with high risk admitted to Department of Hematology, Affiliated Hospital of Panzhihua University was selected as a research subject. Laboratory and imaging examinations were performed to determine the stage and risk of the disease, combined with his medical history and outpatient examination results. After admission, the patient was treated with danazol, thalidomide and prednisone orally, deep intramuscular injection of deferoxamine, subcutaneous injection of erythropoietin (EPO), and suspended red blood cell infusion. In April 2016, the patient received G-PBMNC from his daughter. General condition and treatment safety of patient were observed, and the blood routine test results, transfusion volume of suspended red blood cell and spleen size were monitored. Relevant examination results, diagnosis, treatment and curative effect of this patient were analyzed retrospectively, and related literature was reviewed. This study protocol was approved by the Ethics Committee of Affiliated Hospital of Panzhihua College (No. 11 of the Ethics Examination in 2015), and informed consent was obtained from participant. Results ① After admitted, results of blood routine examination showed that white blood cell count was 2.0×109/L, red blood cell count was 1.5×1012/L, hemoglobin (Hb) value was 39.0 g/L, platelet count was 23.0×109/L, ratio of primitive cells in peripheral blood was 2%. Serum EPO value was more than 774 mIU/mL, and ferritin value was more than 2 250 μg/L. No specimens were taken from the bone marrow puncture. Result of bone X ray radiography showed bone sclerosis. Result of upper abdomen color Doppler ultrasound showed splenomegaly and slight hepatomegaly. The patient was diagnosed as PMF in fibrosis stage with high risk. ② A total of 140 mL of G-PBMNC suspension was isolated from the donor, and transfused to the patient after separation and counting. Number of mononuclear cell (MNC) and CD34+ cell were 3.0×108/kg and 1.6×106/kg, respectively, and acute graft versus host disease (aGVHD) did not develop 1 months after G-PBMNC infusion. ③ Most of the blood routine examination indexes of the patient showed an upward trend after G-PBMNC infusion. 1 and 11 months after G-PBMNC infusion, median white blood cell counts of the patient were 4.0×109/L (3.1×109/L-4.6×109/L) and 3.6×109/L (2.7×109/L-4.0×109/L), and were higher than that of 1.8×109/L (1.3×109/L-2.3×109/L) before G-PBMNC infusion. 8 and 13 months after infusion, median values of Hb were 69.7 g/L (59.2-82.5 g/L) and 70.5 g/L (61.3-84.1 g/L), and were higher than that of 46.8 g/L (33.5-60.3 g/L) before infusion. 6, 11 and 12 months after infusion, median platelet count were 36.5×109/L (22.6×109/L-43.6×109/L), 41.0 ×109/L (29.9 ×109/L-56.7 ×109/L) and 39.0×109/L (25.7×109/L-50.3×109/L), and were also higher than that of 14.0×109/L (7.2×109/L-18.5×109/L) before infusion . ④ Within one month before G-PBMNC infusion, a total of 12 U of suspended red blood cells were transfused; while one month after G-PBMNC infusion, amount of suspended red blood cell infusion decreased to 6.5 U. 3-4 months after infusion, transfusion volume of suspended red blood cell decreased to 1.5 U. 11 months after G-PBMNC infusion, transfusion volume of suspended red blood cell was only 3.5 U, and the patient did not receive blood transfusion for one month. ⑤ There was no progressive enlargement of spleen after infusion of G-PBMNC. Conclusions G-PBMNC could safely improve the routine blood test indexes of PMF patients in fibrosis stage with high risk and reduce the dependence of blood transfusion, so G-PBMNC could be a safe and effective treatment option for fibrotic PMF patients in no condition to allo-HSCT. But this conclusion is limited to the clinical analysis of a single case, and it requires large sample, multi-center, randomized controlled trials for further study and verification. Key words: Allogeneic cells; Transplantation, homologous; Hematopoietic stem cells; Primary myelofibrosis; Therapeutics

Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group

AbstractTo study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16;21), international collaboration is required. Two different types of t(16;21) translocations can be distinguished: t(16;21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16;21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16;21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Münster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n = 23) had significantly lower median white blood cell count (12.5 × 109/L, P = .03) compared with the reference cohort. FUS-ERG rearranged AML (n = 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P = .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] = 5%), significantly lower compared with the reference cohort (51%, SE = 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE = 8%, P = .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE = 8%) in FUS-ERG, 0% (SE = 0%) in RUNX1-CBFA2T3, compared with 32% (SE = 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P = .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk.

Revisiting the complete blood count and clinical findings at diagnosis of childhood acute lymphoblastic leukemia: 10-year experience at a single center

BackgroundHeterogeneity regarding clinical and laboratory findings at diagnosis of acute lymphoblastic leukemia exists. The frequency of complete blood count abnormalities and its combinations, symptoms and physical findings were investigated in Hispanic children from an open population at the diagnosis of acute lymphoblastic leukemia. MethodsThe patient charts and electronic records of under 16-year-old children diagnosed with acute lymphoblastic leukemia over 10 years at a regional hematology center of a university hospital were analyzed to retrieve data concerning the complete blood count at first evaluation. Type and distribution of abnormal data, frequency of symptoms and physical findings at presentation were documented. ResultsThe records of 203 children aged 0–15 years diagnosed with acute lymphoblastic leukemia from 2006 to 2016 were revisited. The results of the blood workup showed a median white blood cell count of 7120×109/L (range: 450–600,000×109/L), and a median hemoglobin concentration of 7.5g/dL (range: 2.4–15.3g/dL), whereas the median platelet count was 47,400×109/L (range: 4000–544,000×109/L). Leukocytosis and leukopenia were present in 36.6% and 36.1% of cases, respectively; anemia was diagnosed in 82.9% children. The order of frequency for major clinical symptoms was fatigue 62%, fever 60%, bone and joint pain 39%, hyporexia 33% and weight loss 21%, while main physical findings were hepatomegaly 78%, splenomegaly 63%, lymphadenopathy 57%, pallor 48%, and purpura 30%. ConclusionData differing from those classically expected at diagnosis of acute lymphoblastic leukemia in children were documented in a cohort of Hispanic children over one decade with a wide spectrum of complete blood count abnormalities, forms of presentation and frequency of physical findings.

Can Patients with Appendicitis in Pregnancy be Operated in Secondary Hospital: A retrospective Study

Appendicitis is the most common non-obstetric cause of acute abdomen in pregnancy. Diagnosis of appendicitis becomes difficult with the change of appendiceal position during pregnancy. Late diagnosis and treatment increase the likelihood of developing perforation. In this study, we aimed to evaluate perioperative outcomes of appendicitis in pregnant patients in secondary hospitals in the light of the literature. 29 pregnant women who performed appendectomy between April 2012 and July 2017 were included in the study. Patients were evaluated according to age, gestational age, white blood cell count, percentage of neutrophil count, C-reactive protein level, ultrasonographic findings, pathologic results, duration of hospitalization and complications. Out of the 29 pregnant patients, 9 (31.0%) patients had surgery during the first trimester, 13 (44.8%) during the second trimester and 7 (24.2%) during the third trimester. Median white blood cell count was 12870 K/mm3 (min-max;7170-25210). Negative laparotomy rate was %31.0. Median duration of hospitalization was 3.24 days (2-7). Morbidity was observed in 2 (6.9%) of 29 patients. Intra-abdominal abscess was observed in one patient and colonic fistula was observed in one patient. Our results demonstrated that appendectomy and follow-up of pregnant patients with acute appendicitis can be performed at secondary hospitals.

Application of apheresis autologous red blood cell transfusion in total hip arthroplasty

Objective To investigate the application of apheresis autologous red blood cell transfusion technology in total hip arthroplasty (THA). Methods From February to July 2016, a total of 191 patients who received THA treatment in the Chinese PLA General Hospital were selected as the research subjects. All patients were randomly divided into study group (n=91) and control group (n=100) by simple random sampling method. Patients in the study group received autologous red blood cell apheresis before THA, while the control group did not collect any autologous blood before THA. The main blood indicators, including red blood cell count, levels of hemoglobin (Hb), white blood cell count, platelet count, were recorded before apheresis in study group or before THA in control group, as well as on the 1st and 3rd day after THA in the 2 groups, respectively. The amount of blood loss during THA, allogeneic transfusion volume on the day of THA, allogeneic blood transfusion rate, allogeneic red blood cell transfusion volume, allogeneic red blood cell transfusion rate, allogeneic plasma transfusion volume, and allogeneic plasma transfusion rate were also observed. Mann-Whitney U test, Wilcoxon signed rank test or χ2 test were used to compare the difference of the above indications between the patients of 2 groups. The procedure of this study is in accordance with the requirements of the revised World Medical Association Declaration of Helsinki in 2013. Informed consent was obtained from each patient. Results ① In this study, there were no statistically significant differences in median red blood cell count of patients between study group before apheresis and that of control group before THA, as well as those of patients between the 2 groups on the 1st and 3rd day after THA (P>0.05). In study group, the median red blood cell count of patients before apheresis was higher than that of patients on the 1st and 3rd day after THA, and the differences were statistically significant (4.5×1012/L vs 4.1×1012/L, Z=-4.043, P 0.05). On the 1st day after THA, the median Hb level of patients in study group was 125 g/L (113-134 g/L), which was higher than 115 g/L (107-135 g/L) of patients in control group, and the difference was statistically significant (Z=-2.302, P=0.021). In study group, the median Hb level of patients before apheresis was higher than those of patients on the 1st and 3rd day after THA, and the differences were statistically significant (137 g/L vs 125 g/L, Z=-6.668, P 0.05). On the 1st day after THA, the median white blood cell count of patients in study group was 11.34×109/L (9.75×109/L-12.76×109/L), which was higher than 10.20×109/L (8.50×109/L-12.39×109/L) in control group, and the difference was statistically significant (Z=-2.399, P=0.016). In study group, the median white blood cell count of patients on the 1st day after THA was higher than those of patients before THA and on the 3rd day after THA, and the differences were statistically significant (11.34×109/L vs 6.15×109/L, Z=-8.272, P 0.05). In study group, the median platelet count of patients before apheresis was higher than those of patients on the 1st and 3rd day after THA, and the differences were statistically significant (229×109/L vs 183×109/L, Z=-7.796, P 0.05). The median volume of allogeneic blood transfusion of patients in study group was 2.6 U (1.0-4.4 U), which was lower than 5.3 U (3.0-7.2 U) of patients in control group, and the difference was statistically significant (Z=-3.903, P 0.05). The rate of allogenic red blood cell transfusion of patients in study group was 52.7%, which was lower than 82.0% of patients in control group, with a statistically significant difference (χ2=18.756, P<0.001). Conclusions The apheresis autologous red blood cell transfusion could meet the needs of clinical blood transfusion in patients with THA, which is safe and effective, and could be promoted during surgery. Key words: Blood transfusion, autologous; Arthroplasty, replacement, hip; Blood component transfusion; Apheresis autologous red blood cell; Autologous blood

A comprehensive phenotyping program for the MRL-lpr mouse lupus model

Abstract MRL/MpJ-Faslpr/J (MRL-lpr) mice develop an autoimmune disease resembling systemic lupus erythematosus, a disease affecting &amp;gt; 1.5 million Americans. The causative mutation, Faslpr, promotes survival of self-reactive lymphocytes, leading to immune proliferation, lymphadenopathy, emergence of anti-DNA antibodies, and fatal immune complex glomerulonephrosis. Like all spontaneous autoimmunity models, MRL-lpr colonies are susceptible to inadvertent selective pressure when mice with absent or delayed phenotypes are bred. We will explain a program for promoting genetic and phenotypic integrity within MRL-lpr breeding colonies. In addition to confirmation of genetic background and Faslpr genotype, breeder phenotypes were assessed at the conclusion of the breeding period. White blood cell counts (WBC) were used to measure lymphoproliferation: at 17 weeks of age, median WBC (103 cells/μL) was 14.2 for females (range = 3.4 – 97.3; N=155) and 10.5 for males (range = 3.7 – 51.4; N=125). Urinalysis to characterize renal damage at 18 weeks of age showed a median albumin/creatinine ratio of 623 for females (range = 1 – 22806; N=163) and 95 for males (range = 1 – 6013; N=123). Median spleen weights (grams) at 18 weeks of age were 0.5464 in females (range = 0.1112 – 2.1348; N=177) and 0.4410 in males (range = 0.2078 – 1.5516; N=135). We will describe a scoring system for clinical signs present at gross necropsy, including appearance of fur/skin, lymph nodes, and organs. We will show that phenotypic integrity can be ensured over time by breeding mice from lineages showing optimal disease development criteria. This program has value beyond breeder assessment, as it can be applied to MRL-lpr mice on study and at conclusion.

Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area.

Patients with septic hip arthritis require surgical drainage, but they can be difficult to distinguish from patients with Lyme arthritis. The ability of synovial fluid white blood cell (WBC) counts to help discriminate between septic and Lyme arthritis of the hip has not been investigated. We assembled a retrospective cohort of patients ≤21 years of age with hip monoarticular arthritis and a synovial fluid culture obtained who presented to 1 of 3 emergency departments located in Lyme disease endemic areas. Septic arthritis was defined as a positive synovial fluid culture result or synovial fluid pleocytosis (WBC count ≥50 000 cells per µL) with a positive blood culture result. Lyme arthritis was defined as positive 2-tiered Lyme disease serology results and negative synovial fluid bacterial culture results. All other patients were classified as having other arthritis. We compared median synovial fluid WBC counts by arthritis type. Of the 238 eligible patients, 26 (11%) had septic arthritis, 32 (13%) had Lyme arthritis, and 180 (76%) had other arthritis. Patients with septic arthritis had a higher median synovial fluid WBC count (126 130 cells per µL; interquartile range 83 303-209 332 cells per µL) than patients with Lyme arthritis (53 955 cells per µL; interquartile range 33 789-73 375 cells per µL). Eighteen patients (56%) with Lyme arthritis had synovial fluid WBC counts ≥50 000 cells per µL. Of the 94 patients who underwent surgical drainage, 13 were later diagnosed with Lyme arthritis. In Lyme disease endemic areas, synovial fluid WBC counts cannot always help differentiate septic from Lyme arthritis. Rapid Lyme diagnostics could help avoid unnecessary operative procedures in patients with Lyme arthritis.

Encephalitis with mGluR5 antibodies: Symptoms and antibody effects.

To report the clinical features of 11 patients with metabotropic glutamate receptor 5 (mGluR5) antibody-associated encephalitis, immunoglobulin G (IgG) subclass, and effects of the antibodies on neuronal mGluR5 clusters. Clinical information was retrospectively obtained from referring physicians. Antibodies to mGluR5 and IgG subclasses were determined with brain immunohistochemistry and cell-based assays. The effects of the antibodies were examined on rat hippocampal neurons with reported techniques. From January 2005 to May 2017, 11 patients (median age 29 years, range 6-75 years, 5 female) were identified. The main clinical features were psychiatric (10), cognitive (10), movement disorders (7), sleep dysfunction (7), and seizures (6). Median modified Rankin Scale score at the peak of the disease was 4; 4 patients required intensive care. Five patients had Hodgkin lymphoma, and 1 had small cell lung cancer. CSF showed pleocytosis (median white blood cell count 22 mm3) in all patients; brain MRI was abnormal in 5, involving limbic (1) or extralimbic (4) regions. Treatments included immunotherapy and/or oncologic therapy; at the last follow-up (median 48 months), 6 patients had complete and 5 had partial recovery. Neurologic relapse occurred in 2 patients. Antibodies were IgG1 alone (4 of 9) or in combination with IgG2 (1 of 9), IgG3 (3 of 9), or both (1). Patients' IgG caused a significant and specific decrease of cell-surface synaptic and extrasynaptic mGluR5 without altering the levels of postsynaptic density protein 95. Anti-mGluR5 encephalitis associates with a complex neuropsychiatric syndrome, not restricted to limbic encephalitis, and can occur without tumor. Patients respond to treatment, but relapses can occur. The antibodies have pathogenic effects altering the levels of cell-surface mGluR5.

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia with FLT3-ITD Mutation

To investigate the clinical characteristics of acute myeloid leukemia(AML) patients with FLT3-ITD(Fms-like tyrosine kinase3, intenal tandem duplication) mutation and their response to treatment. Retrospective analysis of 128 newly diagnosed AML (except type M3) patients was performed between January 2014 and July 2017. Patients were divided into FLT3-ITD mutated group and non-mutated group. Mutation detection was carried out by using polymerase chain reaction(PCR) and gene sequencing analysis. Standard 3 + 7 or CAG regimen were taken as the first induction chemotherapy, 4 cases received sorafenib, overall survival (OS) was calculated by Kaplan-Meier. Ninety-seven patients can be evaluable for clinical data available; 4 patients were FLT3-TKD mutated, which accounted for 4.1%; 19 patients were FLT3-ITD mutated, which accounted for 19.59%(19/97). Median white blood cell count (WBC), percentage of peripheral blasts and LDH value were significantly higher in FLT3-ITD group than those in non-mutated group [64.65(1.07-587.92)×109/L vs 39.68 (0.45-203.81) ×109/L](P<0.01), [69.62(16-99)% vs 36.35(0-92) %](P<0.01 ) and [LDH 526(124-2 729)U/L vs 265(20-1977)U/L](P<0.05), respectively. The frequency of coexisting NPM1 mutation was higher in FLT3-ITD group than that in non-mutated group [36.8(7/19)% vs 6.8 (5/74) %](P<0.01). The CR+PR was lower in FLT3-ITD group than that in non-mutated group [31.6(6/19)% vs 64.9 (48/74)%](P<0.05). OS in FLT3-ITD group was significantly shorter than that in non-mutated group (5 vs 18 months)(P<0.05). There is no significant difference in OS between FLT3-ITD concomitant with and without NPM1 mutation groups(5 vs 5 months)(P>0.05). The median OS was 13 months for the FLT3-ITD patients taking sorafenib. The FLT3-ITD is a common mutation in AML, FLT3-ITD mutated AML is more likely concomitant with NPM1 mutation with higher number of WBC, percentage of peripheral blasts and LDH value, thus CR is low after the 1st treatment and survival is poor.