Delaying therapy in Pts age ≥ 65 with untreated AML

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6560-6560
Author(s):  
E. Estey ◽  
F. Giles ◽  
G. Garcia-Manero ◽  
H. Kantarjian
Keyword(s):  
Multivariate Analysis ◽  
Supportive Care ◽  
Death Rate ◽  
Performance Status ◽  
Normal Karyotype ◽  
Potential Influence ◽  
Death Rates ◽  
And Performance ◽  
Wbc Count ◽  
Referring Physicians

6560 186 pts age ≥ 65 with untreated normal karyotype AML given ara-C-containing Rx at MDA from 1996–2005 had course 1(C1) CR and death rates of 57% and 13%, while in 133 pts with abnormalities of chromosomes 5 and/or 7 (−5/−7) the C1 CR rate was essentially identical to the C1 death rate (30% and 27%). Knowledge of cytogenetics, while thus valuable in planning Rx, may not be available for ≥ 1 week after presentation, raising questions as to the advisability of waiting this long to begin Rx. We previously reported a multivariate analysis in 197 pts, median age 64 and with presenting WBC < 50,000, given idarubicin + ara-C for untreated AML at M.D. Anderson between 2001- and 2004, finding that the independent predictors of CR were age and cytogenetics but not the number of days from MDA presentation to MDA Rx (Estey et al. 2004 ASH meeting,abstract #879). Because Rx was delayed for > 1 week in only small numbers of older pts we now extend these observations to 684 pts age ≥ 65 with untreated AML and presenting WBC < 50,000 given induction Rx (± ara-C) at MDA since 1996. Time from MDA presentation to Rx was < 1 week in 423, 1–2 weeks in 126, 2 weeks-1 month in 80, and > 1 month in 55. This time was not affected by age, bilirubin, creatinine, or by whether induction Rx contained ara-C. However, 7% of pts Rxed within 2 weeks of diagnosis had performance status 3–4 vs. only 1% of pts Rxed after a delay of > 14 days (p = 0.008), leading us to limit analysis to pts with performance status 0–2. Results were as follows: Although CR rates were higher, results were qualitatively similar considering only pts given ara-C-containing Rx. Recognizing the potential influence of unrecorded covariates, the data suggest that delay of Rx in pts age ≥ 64 with untreated AML, WBC count < 50,000, and performance status < 3 does not affect outcome of induction therapy, a possibility given more credence by the several days that elapse between diagnosis of AML by referring physicians and MDA presentation. Delaying Rx allows knowledge of cytogenetic status, thus permitting investigational Rx, or supportive care only, to be directed to pts with -5/-7. [Table: see text] No significant financial relationships to disclose.

Clinical Significance of Free Circulating CD34 in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4495-4495
Author(s):  
Menna Hodge ◽  
Francis Giles ◽  
Adam Abdool ◽  
Susan O’Brien ◽  
Michael Keating ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Signal Transduction Pathway ◽  
Leukemic Cells ◽  
Neural Cells ◽  
And Performance ◽  
Wbc Count ◽  
Acute Myeloid

Abstract CD34 is an approximately 116-kd glycophosphoprotein expressed in hematopoietic progenitor cells, endothelial cells, and some mesenchymal and neural cells. CD34 is a typical adhesion molecule capable of inducing the cell signal transduction pathway leading to adhesion and differentiation. We used a newly developed bead-based assay to measure cell-free circulating CD34 (cCD34) in the plasma of patients with acute myeloid leukemia (AML; n = 98) and myelodysplastic syndrome (MDS; n = 50). Levels of cCD34 were significantly higher in AML (median 10983, range: 844–100,4191 U/10 μl than in MDS (median: 8749, range:102–791,350 U/10 μl) patients (P&lt;0.01). cCD34 levels were higher among patients with high-risk cytogenetic abnormalities in AML (P = 0.01) but not MDS (P = 0.92). When grouped together, AML and MDS patients with cCD34 levels higher than the median (10,845 U/μl) had significantly shorter survival than those with lower levels (P = 0.01). This association was independent of cytogenetic grouping, age, and performance status. cCD34 levels did not correlate with percent of blasts or CD34+ cells but did correlate with WBC count (R = 0.36) in patients with AML, suggesting that cCD34 reflects the overall leukemia load. Although further study is needed for confirmation, cCD34 appears to result from turnover of leukemic cells and may affect the activation of certain pathways, therefore influencing survival and clinical outcome. Figure Figure

Ki67 labelling index and performance status are predictive factors of response to concomitant radiochemotherapy (RCT) in esophageal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15119-15119
Author(s):  
J. F. Seitz ◽  
L. Dahan ◽  
E. Ressiot ◽  
A. Liprandi ◽  
R. Giorgi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Predictive Factors ◽  
Predictive Value ◽  
Performance Status ◽  
Complete Response ◽  
Complete Pathological Response ◽  
Esophagus Cancer ◽  
Concomitant Radiochemotherapy ◽  
Good Performance Status ◽  
And Performance

15119 Background: In oesophageal cancer, preoperative RCT allows a prolonged survival for patients achieving a complete pathological response at time of surgery. However, predictive factors for complete response to RCT are not well known. The aim of this retrospective study was to identify clinical and histopathological factors predictive of complete endoscopic response (CER) in patients treated by RCT before surgery or as exclusive treatment for esophagus cancer. Methods: from 2000 september to 2006 march, 56 patients with esophagus cancer (35 squamous cell carcinoma (SCC), 20 adenocarcinoma (ADK), 1 undifferentiated) were treated by RCT (45–50 grays /25 fractions / 5 weeks and 2 courses of 5FU-CDDP at weeks 1 and 5). 16 patients subsequently underwent oesophageal resection. Endoscopy with biopsies was performed 3 weeks after the end of RCT. Clinical, biological, radiological and pathological (including EGFR, p53 and Ki67 immunostaining) parameters were included in univariate and multivariate analysis to determine predictive factors for CER. Results: CER was observed in 31 out of 54 appraisable patients (57.4%). In both univariate and multivariate analysis, 2 factors were predictive of complete endoscopic response: good performance status (PS 0 vs 1–2: OR = 15.75 - p=0.01) and higher expression of Ki67 (>=18 vs <18: OR = 4.46 - p=0.04).A pCR was seen in 7 (44%) of the 16 operated patients. Positive predictive value of endoscopy for pCR was 87.5% (IC95%: 47.4–99.7%), and negative predictive value was 100% (IC95%: 68.7–100%). Predictive factors of pCR were: a complete endoscopic response (p<0.01), a complete CT-scan response (p=0.03) and a good performance status (p=0.04). Median survival in all 56 patients was 40 months. Pejorative prognostic variables for survival in multivariate analysis were adenocarcinoma histology (RR=3.11; p=0.03), and performance status (RR=4.79; p=0.04). Conclusions: In our study, a good performance status and surexpression of Ki67 were independent predictive factors for complete endoscopic response after RCT. The 2 prognostic factors for survival are histologic type and performance status. No significant financial relationships to disclose.

Pharmacogenetic biomarkers for predisposition to toxicity to adjuvant FOLFOX/XELOX in colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 390-390
Author(s):  
Pilar Garcia Alfonso ◽  
Andres J. Muñoz ◽  
Montse Blanco Codeisido ◽  
Daniel Lopez-Trabada Ataz ◽  
Lucia Cortejoso-Fernandez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Adverse Reactions ◽  
Performance Status ◽  
Univariate Analysis ◽  
Chi Square ◽  
Hand Foot Syndrome ◽  
Chi Square Test ◽  
And Performance ◽  
Prior Application

390 Background: 5-fluorouracil and capecitabine are the gold standards in colorectal cancer (CRC) treatment and are often combined with oxaliplatin (FOLFOX and XELOX chemotherapy, respectively). Our purpose was to analyze associations between severe adverse reactions to these regimes and polymorphisms in genes related to these drugs Methods: Retrospective study with 47 adult CRC patients treated with adjuvant FOLFOX/XELOX. 20 polymorphisms in 14 genes were selected: 6 genes [XRCC1 (rs25487), ERCC2 (rs131181), ERCC1 (rs11615), GSTP1 (rs1695), EGFR (rs4559542) and GSTT1 (copy number variation)] related to the pharmacokinetics and dynamics of oxaliplatin and 8 related to fluoropyrimidines [MTHFR (rs1801131 and rs1801133), DPYD (rs2297595 and rs3918290), TYMS (rs34743033 and rs34489327), ABCB1 (rs1128503, rs2032582 and rs1045642), ABCC4 (rs4148551 and rs3742106), ABCC5 (rs3805114), CYP2A6 (rs3742106 ) and CDA (rs2072671)]. Linear by linear association chi-square test (SPSS v.18.0.) was used to study associations. A multivariate analysis including sex and performance status was also conducted. p< 0.05 was considered significant. Results: Mean age was 62 (SD: 12) years and 78.7% male. Univariate analysis: statistically significant associations were obtained between rs11615 (ERCC1), neutropenia and hand-foot syndrome; rs3742106 (CYP2A6) and neutropenia; rs34743033 and rs34489327 (TYMS) and nausea/vomiting; and CNV of GSTT1 and neutropenia. Multivariate analysis: statistically significant associations were obtained between rs3742106 (CYP2A6) and neutropenia (GT vs. TT: OR, 0.042, 95% CI, 0004-0499, p = 0.012); rs2297595 (DPYD) and nausea/vomiting (GA vs AA: OR, 0.051, 95% CI, 0003-0772, p = 0.032); and rs11615 (ERCC1) and neutropenia (CC vs CT / TT: OR, 0.099, 95% CI, 0016-0615, p = 0.013) Conclusions: These results could help oncologists reduce adverse reactions associated to FOLFOX and XELOX chemotherapy by giving patients the best possible option, thus, improving their quality of life. Bigger cohorts are needed to verify the polymorphisms in ERCC1, CYP2A6, TYMS, DPYD and GSTT1 prior application in clinical practice.

scholarly journals Soluble Interleukin-2 Receptor and C-Reactive Protein Levels Are Associated with the Efficacy of Bendamustine As a Salvage Treatment for Indolent Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1797-1797
Author(s):  
Yukiko Kawaguchi ◽  
Bungo Saito ◽  
Maasa Abe ◽  
Yuta Baba ◽  
Sou Murai ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Outcome ◽  
Follicular Lymphoma ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Indolent Lymphoma ◽  
Purine Analogue ◽  
Laboratory Parameters ◽  
Wbc Count ◽  
Serum Crp

Abstract Background: Bendamustine has demonstrated a favorable efficacy and toxicity profile in relapsed or refractory indolent lymphoma. Limited information is available regarding the prognostic factors (particularly laboratory parameters) of bendamustine treatment, although studies have shown a relationship between the hampered effect of bendamustine and an increase in lactate dehydrogenase (LDH) levels. Therefore, we retrospectively evaluated clinical and laboratory factors immediately prior to initiating bendamustine treatment and analyzed its correlation with the clinical outcome among patients with relapsed or refractory indolent lymphoma. Patients and methods: We analyzed 55 relapsed or refractory indolent lymphoma patients who had been treated with bendamustine alone (n = 19) or rituximab plus bendamustine (n = 36) at our hospital from 2000 to 2015. The median age at diagnosis was 65 years and the median follow-up period was 552.5 days. Histological analysis revealed follicular lymphoma (n = 21), mantle cell lymphoma (n = 10), MALT lymphoma (n = 7), lymphoplasmacytoid lymphoma (n = 5), and other low-grade B cell lymphomas (n = 4). We further analyzed the relationships between the clinical outcome [overall response rate (ORR), complete response (CR), progression-free survival (PFS), and overall survival (OS)] and clinical data, including sex, patient age (≥65 years), performance status (≥2), IPI (≥HI), FLIPI (≥HI), no. of previous therapies (≥2), prior purine analogue treatment, response to last treatment, and laboratory parameters [white blood cell count (≥5000/µl), lymphocyte count (≥1000/µl), platelet count (≥10000/µl), LDH (elevated or normal), sIL-2R (elevated or normal), and CRP (elevated or normal)], before starting bendamustine treatment. Results: The median number of cycles of bendamustine was 4 (range: 1-8). The ORR was 80.3% with a CR of 39.2%. Moreover, the CR rate was significantly worse in patients who had elevated sIL-2R and CRP, high or high-intermediate IPI scores, and a high WBC count (P = 0.002, P < 0.001, P = 0.072, and P < 0.046, respectively). Among follicular lymphoma patients, elevated CRP was only associated with a low CR rate (P = 0.028). In multivariate analysis, sIL-2R, CRP, and a high WBC count were all significantly associated with a worse CR rate (P = 0.044, P = 0.002, and P = 0.032, respectively). The 1- and 2- year OS rates were 80.3% and 76.1%, respectively. The OS was significantly higher in a group of the patients who obtained CR after bendamustine, were treated with rituximab plus bendamustine, and did not receive prior purine analogue treatment (P = 0.007, P = 0.008, and P < 0.001, respectively). An elevated CRP was associated with worse OS (P = 0.055). In multivariate analysis, only CR after bendamustine was significantly associated with improved OS (P = 0.023). The 1- and 2-year PFS rates were 69.2% and 60.5%, respectively. PFS was significantly better in patients who obtained CR after bendamustine treatment, had a normal CRP, had not received more than 2 previous therapies, and had a good performance status (P < 0.001, P = 0.007, P = 0.031, and P = 0.033, respectively). In multivariate analysis, any prognosis factors were significantly associated with PFS. Conclusion: This is the first study to demonstrate a correlation between laboratory parameters (i.e., CRP and sIL-2R) and the clinical outcome in patients with relapsed or refractory indolent lymphoma who were treated with bendamustine. In this study, CRP and sIL-2R levels as well as the WBC count were associated with the CR rate. In addition, the CRP levels were associated with OS and PFS, but LDH levels were not associated with any clinical outcomes. Previous studies have reported that the elevation of serum CRP and sIL-2R levels were associated with poor OS or PFS in patients who were treated with rituximab combined with CHOP in diffuse large B-cell lymphoma or follicular lymphoma. Our study indicates that serum CRP and sIL-2R levels are also important laboratory parameters for patients with indolent lymphoma who underwent bendamustine treatment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic Value of PD-L1 Expression on Immune Cells or Tumor Cells for Locally Advanced Esophageal Squamous Cell Carcinoma in Patients Treated With Neoadjuvant Chemoradiotherapy

2021 ◽  
Author(s):  
Ta-Chen Huang ◽  
Cher-Wei Liang ◽  
Yu-I Li ◽  
Jhe-Cyuan Guo ◽  
Chia-Chi Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Multivariate Analysis ◽  
Esophageal Squamous Cell Carcinoma ◽  
Tumor Cells ◽  
Immune Cells ◽  
Prognostic Value ◽  
Performance Status ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
And Performance

Abstract Purpose Programmed death-ligand 1 (PD-L1) expression may influence the prognosis of patients with localized esophageal cancer. The current study compared the prognostic value of PD-L1 expression between tumor cells and immune cells. Methods Archival esophageal tumor tissue samples were collected from patients who received paclitaxel and cisplatin-based neoadjuvant chemoradiotherapy (CRT) for locally advanced esophageal squamous cell carcinoma (ESCC) in 3 prospective phase II trials. PD-L1 expression on tumor and immune cells was examined immunohistochemically by using the SP142 antibody and scored by 2 independent pathologists. The association of PD-L1 expression with patients’ outcomes was analyzed using a log-rank test and Cox regression multivariate analysis. Results A total of 100 patients were included. PD-L1 expression on tumor cells was positive (≥1%, TC-positive) in 55 patients; PD-L1 expression on immune cells was high (≥5%, IC-high) in 30 patients. TC-positive status was associated with poor overall survival (OS) (HR: 1.63, P = .035), whereas IC-high status was associated with improved OS (HR: 0.44, P = .0024). Multivariate analysis revealed that TC-positive, IC-high, and performance status were independent prognostic factors for progression-free survival and that IC-high and performance status were independent factors for OS. Furthermore, the combination of IC-high and TC-negative status was associated with the optimal OS, whereas that of TC-positive and IC-low status was associated with the worst OS. Conclusion PD-L1 expression on tumor and immune cells may have different prognostic value for patients with locally advanced ESCC receiving neoadjuvant CRT. A combination of these 2 indexes may further improve the prognostic prediction.

Untreated Patients with Acute Myeloid Leukemia, Age 50–59 Years and Performance Status 2 Should Be as Eligible for Targeted Therapy as Older Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2864-2864
Author(s):  
Apostolia M. Tsimberidou ◽  
Hagop M. Kantarjian ◽  
Stefan Faderl ◽  
Sherry Pierce ◽  
Emil J. Freireich ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Death Rates ◽  
Targeted Treatments ◽  
High Death ◽  
And Performance ◽  
Acute Myeloid

Abstract Background: The early mortality rates in older patients (generally defined as those > 60 years) following standard therapy for acute myeloid leukemia (AML), has spurred numerous trials of “targeted” treatments, typically limited to this age group. Here we examine whether younger patients with Zubrod performance status (PS) 2 might also be candidates for these therapies. Patients and Methods: We reviewed the records of 1841 patients 40 years or older with newly diagnosed AML (no acute promyelocytic leukemia) who received cytarabine-containing therapy at M. D. Anderson from 1980 to 2007. We chose patients with the following pretreatment characteristics because they are conventional criteria for entry onto trials of new therapies: PS 0–2, bilirubin < 2 mg/dL, and creatinine < 2 mg/dL. We calculated death rates by age and PS at 28 and 42 days after initiation of induction therapy. Results: Induction death rates in patients with AML by age and performance status The 28-day death rates in patients age 50–59 years with PS 2 were similar to those in patients ≥ 60 years with PS 0–1, and the 42-day death rates in the patients age 50–59 years with PS 2 were similar to those in patients age 60–79 with PS 0–1. Conclusion: Because of the high death rates following AML therapy in patients age 50–59 with PS 2, these patients should be eligible for targeted treatments now limited to older patients. Age, yrs Performance Status No. of Patients Dead by day 28, % Dead by day 42 % 40–49 0–1 288 7 9 40–49 2 38 5 5 50–59 0–1 405 4 6 50–59 2 85 14 15 60–69 0–1 423 8 11 60–69 2 111 17 17 70–79 0–1 301 12 16 70–79 2 124 23 33 ≥80 0–1 45 13 20 ≥ 80 2 21 38 43

Patient Characteristics and Early Death Predictors in Acute Promyelocytic Leukaemia Patients; Experience from United Arab Emirates (UAE)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4963-4963
Author(s):  
Mariam Rashed Alzaabi ◽  
Inaam bashir Hassan ◽  
Martin S Tallman ◽  
Arif Alam ◽  
Khalid Al qawasmeh ◽  
...  
Keyword(s):  
United Arab Emirates ◽  
Death Rate ◽  
Chromosomal Abnormalities ◽  
Early Death ◽  
Patient Characteristics ◽  
Developed Countries ◽  
Published Data ◽  
Death Rates ◽  
Wbc Count ◽  
Additional Chromosomal Abnormalities

Abstract Background: Acute promyelocytic leukemia (APL) is a highly curable subtype of acute myeloid leukemia (AML). APL has unique morphological, cytogenetic and molecular characteristics. Although extensive data regarding APL are available from developed countries only few studies have been published from developing countries. They describe higher early death rates with lower complete remission rate compared to patients from developed countries. In a retrospective analysis, we evaluated the characteristics features at presentation and predictor of early death in 67 patients with APL diagnosed between 2000 and 2015 at two centers in UAE. To our knowledge there are no published data on APL early death rates from the United Arab Emirates (UAE) Patients and Methods: All patients age >15 years with a newly diagnosis of APL between January 2000 and January 2013 at Tawam hospital and Sheikh Khalifa Medical City (SKMC) were included. The initial diagnosis was typically based on clinical, morphological & phenotypic (negative expression of CD34 and HLA-DR but positive expression of CD2 and CD9) suspicion of APL. Subsequently the diagnosis was confirmed with genetic study for detection of t(15:17). Oral ATRA was immediately started at the standard dose 45 mg/m2 per day in addition to supportive care to correct the coagulopathy (fresh-frozen plasma, cryoprecipitate to maintain fibrinogen at >1.5 g/l, and platelets was maintained at >30x109/l). Early death was defined as death within 30 days of a patient being diagnosed with APL. Data were analyzed using SPSS version 21 (IBM SPSS Inc., Chicago, IL). Results: The median age was 33 years (15 - 57) with only 18 (26.9%) of the patients were older than 40 years. Patients were more likely to be male (42, 62.7%), present with bleeding (53, 80.3%) at the time of diagnosis, have a WBC count greater than 10x109/L in 59.9% while in 40% of the patients it was < 5 x109/L. They tend to have platelet count < 30x109/L in 76.1%, high INR in 66.7% and < 1.5g/L fibrinogen in two third of them. 69.2% of them had bcr1 and 10 of the patients (14.9%) had t(15:17) with additional chromosomal abnormalities include monosomy7 (2 patients), trisomy 8 (1 patients), del 9 (1 patients), ring chromosome 6 (2 patients), der 21 (1 patients) and complex karyotype (3 patients). Early death rate was 11.9%(8/67 patients). In a univariate analysis of the prognostic factors, early-deaths occurred significantly more frequent in patients who were >40 years of age (27.8% versus 6.1%; p= 0.015), those who presented with fever (21.2% versus 2.3%; p=0.030), WBC count >20 x 109/L (26.1% versus 4.5%; p=0.010), high INR (17.7% versus 0.0%; p=0.047), high APTT (40% versus 7.4%; p=0.021) at the time of diagnosis. Although fibrinogen level <1.5g/L was not identified as a significant predictor (21.1% versus 5.1%; p=0.062) of early death, a level of <1.0 g/L emerge as a significance (30.0% versus 4.3%; p=0.010) predictor in addition to the breakpoints other than bcr1 (25.0% versus 3.7%; p=0.043). Time to start of ATRA (>24h versus within 24h) therapy failed to show statistical significance (13.3% versus 12.5%; p=0.9). Patients with WBC count <5.0x109/L have tendency to less frequent early death (3.7% versus 17.5%; p=0.08). None of the patients with additional chromosomal abnormalities experienced early death (0.0% versus 14.0%). However the difference was not statistically significant (p=0.26). Conclusion: The patient characteristics of UAE APL patients at presentation are similar to other published data. Early death rate is comparable to that published from developed countries. Our data support that coagulopathy at presentation is a major contributor to early death and that treatment of APL with improvement of early death rate is feasible at centers in developing countries provided access to facilities for aggressive supportive care. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Outcome of Low-Risk Childhood B-Cell Precursor ALL Treated with the Japan Association of Childhood Leukemia Study (JACLS) ALL-02 Trial

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1604-1604
Author(s):  
Yoshihiro Takahashi ◽  
Toshihiko Imamura ◽  
Ikuya Usami ◽  
Keiko Yumura-Yagi ◽  
Soichi Suenobu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multivariate Analysis ◽  
Poor Prognosis ◽  
Childhood Leukemia ◽  
Risk Group ◽  
Normal Karyotype ◽  
Low Risk ◽  
Intensive Chemotherapy ◽  
Chemotherapeutic Regimen ◽  
Wbc Count

Abstract Background: It is important to establish proper intensity of chemotherapeutic regimen for low risk group of childhood B-precursor ALL (BCP-ALL) to avoid late effects. For this purpose, in Japan Association of Childhood Leukemia study (JACLS) ALL-02 clinical trial, we defined standard risk (SR) group as the patients ranged from 1 to 10 years showing white blood cell (WBC) count of less than 10,000/μL at the diagnosis without predonisolone poor responder, t(4;11), t(1;19) and CNS3 to treat with less intensive chemotherapy (JACLS ALL02 SR protocol). Herein, we report the outcome of JACLS ALL02 SR protocol and analyzed prognostic factors to identify super low risk group which is curable by less intensive chemotherapy. Patientss and treatment: JACLS ALL02 SR protocol consisted of early phase therapies for total 4 months including an induction therapy using vincristine (VCR), steroids, pirarubicin (THP-ADR), and L-asparaginase (L-asp) for 4 weeks, a consolidation therapy using cyclophosphamide and a combined administration of cytarabine and dexamethasone (DEX) or 6-mercaptopurine (6-MP), a sanctuary therapy with only two cycles of high-dose methotrexate (MTX) of 3g/m2, one course of 4 drugs re-induction therapy and maintenance phase with 6-MP and oral MTX combined with VCR and PSL every 5 weeks by the end of the second year. In addition, total of 12 times of triple intrathecal therapy were administered by the end of the first year. Estimation of event free survival (EFS) and overall survival (OS) was performed using the Kaplan-Meier method and the differences were compared using the log-rank test. Multivariate analysis was performed using a Cox regression model. Results: 1252 newly diagnosed ALL patients were enrolled from April 2002 to May 2008 in JACLS ALL02 clinical trial, which include 388 patients (192 males and 196 females) in SR group (31.0%). The median age at diagnosis was 4.2 years (range, 1.0 to 9.9 years) and the median WBC count was 3,700/μL (range, 370 to 9,984 /μL). The median follow-up time was 6 year and 5 months. 4y / 8y EFS and OS (±SE) of the SR group are 91.5±1.4% / 89.4±1.7% and 97.9±0.7% / 95.2±1.2%, respectively. 4y / 8y EFS of the patients of 1 to 5 years old (n=300) and 6 to 9 years old (n=88) are 93.5±1.4% / 93.0±1.5% and 84.9±3.9% / 75.8±5.8%, respectively (log rank p=0.0003). 4y / 8y EFS of the patients with day 15 M1 marrow (n=287 ) was 92.8±1.6% / 91.6±1.8%, while those of the patients with day 15 M2 marrow (n=101) was 88.0±3.3% / 83.7±3.9% (log rank p=0.0446). When 388 patients were further classified into 4 subgroups based on genetic abnormalities, such as ETV6-RUNX1 (n=89, 22.9%), high hyperdiploid (HHD) (n=97, 25%), normal karyotype (n=147, 37.9%), and others (n=55, 14.2%), 4y-EFS/OS of each group was 97.6±5.9 /100% (ETV6-RUNX1), 91.5±2.9 /100% (HHD), 89.6±2.5 /95.1±1.8% (normal karyotype), and 86.9±4.6 /98.2±1.8% (others), suggesting poor EFS of B-others group. When HHD subgroup was divided into two groups, such as triple trisomy (TT; n=35) (trisomy of chromosome 4,10,17) and non-TT (n=62), 4y-EFS of each sub-group was 100% and 84.5±4.5%, respectively (log rank p=0.0161). Interestingly, day 15 M2 marrow was associated with poor 4y/8y EFS only in the normal karyotype subgroup (day 15 M1 vs M2 92.0±2.6% / 90.2±3.1% vs, 81.3±6.9% / 77.2±7.7%, log rank p=0.0497). The rates for NCI-CTC grade 4 infection, allergy, increase of transaminase were 1.80%, 0.26%, and 22.9%, respectively. Multivariate analysis identifies the patients of 6 to 9 years old (HR=3.178, p=<0.001) as a predictor of poor prognosis in EFS and day 15 M2 marrow (HR=3.273, p=0.027) and B-others subgroup (HR=11.1, p=0.0017) as predictors of poor prognosis in OS. Discussion: Although JACLS ALL-02 SR protocol was less intensive chemotherapeutic regimen compared to the contemporary protocols used for NCI-SR patients, good outcome of the 4y EFS and OS (91.5±1.4 % and 97.9±0.7 %) was achieved with good feasibility. Because the specific genetic subgroups such as B-others and HHD without TT were associated with relatively poor outcome, those patients should be treated with more intensive chemotherapy, especially for the patients showing initial poor response (day 15 M2). On the other hand, ETV6-RNUX1 and TT subgroups showed excellent outcome. Thus, appropriate reduction of therapy should be explored for these subgroups. Disclosures No relevant conflicts of interest to declare.

The impact of climate temperature on counts, recovery, and death rates due to SARS-CoV-2 in South Africa. (Preprint)

2020 ◽  
Author(s):  
Neven Chetty ◽  
Bamise Adeleye ◽  
Abiola Olawale Ilori
Keyword(s):  
South Africa ◽  
South African ◽  
Death Rate ◽  
Western Cape ◽  
Warm Climate ◽  
The South ◽  
Recovery Rates ◽  
Death Rates ◽  
Online Resource ◽  
The Impact

BACKGROUND The impact of climate temperature on the counts (number of positive COVID-19 cases reported), recovery, and death rates of COVID-19 cases in South Africa's nine provinces was investigated. The data for confirmed cases of COVID-19 were collected for March 25 and June 30, 2020 (14 weeks) from South Africa's Government COVID-19 online resource, while the daily provincial climate temperatures were collected from the website of the South African Weather Service. Our result indicates that a higher or lower climate temperature does not prevent or delay the spread and death rates but shows significant positive impacts on the recovery rates of COVID-19 patients. Thus, it indicates that the climate temperature is unlikely to impose a strict limit on the spread of COVID-19. There is no correlation between the cases and death rates, an indicator that no particular temperature range is closely associated with a faster or slower death rate of COVID-19 patients. As evidence from our study, a warm climate temperature can only increase the recovery rate of COVID-19 patients, ultimately impacting the death and active case rates and freeing up resources quicker to enable health facilities to deal with those patients' climbing rates who need treatment. OBJECTIVE This study aims to investigate the impact of climate temperature variation on the counts, recovery, and death rates of COVID-19 cases in all South Africa's provinces. The findings were compared with those of countries with comparable climate temperature values. METHODS The data for confirmed cases of COVID-19 were collected for March 25 and June 30 (14 weeks) for South African provinces, including daily counts, death, and recovery rates. The dates were grouped into two, wherein weeks 1-5 represent the periods of total lockdown to contain the spread of COVID-19 in South Africa. Weeks 6-14 are periods where the lockdown was eased to various levels 4 and 3. The daily information of COVID-19 count, death, and recovery was obtained from South Africa's Government COVID-19 online resource (https://sacoronavirus.co.za). Daily provincial climate temperatures were collected from the website of the South African Weather Service (https://www.weathersa.co.za). The provinces of South Africa are Eastern Cape, Western Cape, Northern Cape, Limpopo, Northwest, Mpumalanga, Free State, KwaZulu-Natal, Western Cape, and Gauteng. Weekly consideration was given to the daily climate temperature (average minimum and maximum). The recorded values were considered, respectively, to be in the ratio of death-to-count (D/C) and recovery-to-count (R/C). Descriptive statistics were performed for all the data collected for this study. The analyses were performed using the Person’s bivariate correlation to analyze the association between climate temperature, death-to-count, and recovery-to-count ratios of COVID-19. RESULTS The results showed that higher climate temperatures aren't essential to avoid the COVID-19 from being spread. The present results conform to the reports that suggested that COVID-19 is unlike the seasonal flu, which does dissipate as the climate temperature rises [17]. Accordingly, the ratio of counts and death-to-count cannot be concluded to be influenced by variations in the climate temperatures within the study areas. CONCLUSIONS The study investigates the impact of climate temperature on the counts, recovery, and death rates of COVID-19 cases in all South Africa's provinces. The findings were compared with those of countries with comparable climate temperatures as South Africa. Our result indicates that a higher or lower climate temperature does not prevent or delay the spread and death rates but shows significant positive impacts on the recovery rates of COVID-19 patients. Warm climate temperatures seem not to restrict the spread of the COVID-19 as the count rate was substantial at every climate temperatures. Thus, it indicates that the climate temperature is unlikely to impose a strict limit on the spread of COVID-19. There is no correlation between the cases and death rates, an indicator that there is no particular temperature range of the climatic conditions closely associated with a faster or slower death rate of COVID-19 patients. However, other shortcomings in this study's process should not be ignored. Some other factors may have contributed to recovery rates, such as the South African government's timely intervention to announce a national lockout at the early stage of the outbreak, the availability of intensive medical care, and social distancing effects. Nevertheless, this study shows that a warm climate temperature can only help COVID-19 patients recover more quickly, thereby having huge impacts on the death and active case rates.

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