Management of Acute Myeloid Leukemia (AML) in First Relapse: Retrospective Analysis about 101 Adults Cases Receiving Homogeneous First-Line Therapy. Impact of Prognostic Factors and Treatment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 882-882
Author(s):  
Cecile Fohrer ◽  
Brigitte Witz ◽  
Jean Luc Harousseau ◽  
Francis Witz ◽  
Shanti Ame ◽  
...  

Abstract We retrospectively analyzed impact of prognostic factors and salvage therapy in 101 patients (pts) with AML in 1st relapse. All pts were treated as 1st line according protocols GOELAMs 1 (87–94) or 2 (95–99). They all achieved complete remission after one (85%) or two (16%) induction with a combination of anthracycline and cytarabine. Consolidation therapy included one course of high-dose cytarabine (HiDAC) and a second consolidation (amsacrine-VP16) or, for a subset of pts, intensification with allogeneic or autologous stem cell transplantation (SCT). Data were collected in 3 of the centers participating to these trials. Main characteristics of pts at initial diagnosis were: median age : 39 y (range 17–64); sex : 55 male, 46 female; WBC count > 30 000/μl in 42 (42%) pts; 16/85 (18%) pts had unfavorable karyotype. Median duration of 1st complete remission (CR1) was 10 months (range: 1–101). Duration of CR1 was shorter than 6 months in 22 (22%) pts, between 6 and 12 months in 41 (40%) pts and longer than 12 months in 38 (38%) pts. At time of 1st relapse, median age was 40 y (range 18–66) and 10/38 (26%) unfavorable karyotype. There were no specific recommendations in the GOELAMs protocols for the second line therapy: modalities of treatment were therefore left to investigator’s decision. First step of relapse treatment was based on intensive chemotherapy in 79 (79%) pts including 55 pts who received a regimen containing HiDAC (Group 1) and 24 pts who received a chemotherapy without HiDAC (Group 2). Eight pts received an autologous SCT (4 pts) or an allogeneic SCT (4 pts) without any previous salvage chemotherapy (Group 3). One pt received gemtuzumab ozogamicin and thirteen pts received only oral chemotherapy and/or supportive care (Group 4). Fifty-seven pts (56%) achieved a second CR. Response rate and median survival according to initial therapy of relapse are shown in the following table. Differences are not significant. Complete response (%) Median survival (months) Group 1 (n = 55) 39 (71%) 11.5 Group 2 (n = 24 10 (42%) 8 Group 3 (n = 8) 6 (75%) 7.5 Group 4 (n = 14) 2 (14%) 3.5 Twenty seven pts out of the 49 pts who achieved a CR2 after intensive chemotherapy (Group 1 and 2) received subsequent intensification with either an allogeneic SCT (7 pts) or an autologous SCT (20 pts). Median survival of these pts subsequently transplanted was 18 months compared to only 10 months in the 22 pts of group 1 and 2 who did not receive a subsequent transplantation. Difference is not significant (log rank test, p = 0.65). Nine (33%) of the 27 transplanted pts are alive more than 36 months after relapse (range 41–120). Univariate analysis demonstrated that adverse prognosis factors on survival at 1st relapse were duration of RC1 shorter than 12 months (p= 0.005)and complex cytogenetic abnormalities (p= 0.0086). Conclusion: Intensive chemotherapy including HiDAC at 1st relapse in AML in adults provided a high rate of complete response. Intensification with SCT after CR2 was obtained can provide a very long survival in a limited number of pts. At 1st relapse, adverse prognostic factors on survival were short CR1 and unfavorable karyotype. Risk-adapted of AML in first relapse may therefore be warranted. Figure Figure

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2644-2644
Author(s):  
Etsuko Yamazaki ◽  
Naoto Tomita ◽  
Satoshi Koyama ◽  
Kumiko Kishimoto ◽  
Eriko Ogusa ◽  
...  

Abstract Abstract 2644 Background: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a rare subtype in Western countries but is more frequent in East Asia or in Central and South America. The response to conventional chemotherapy is not good, generally resulting in a poor prognosis. Several Asian investigators reported that the International Prognostic Index (IPI) score, Prognostic Index for PTCL-U (PIT) and Korean index, including regional lymph node involvement, clinical stage, presence of B symptom and serum lactate dehydrogenase (LDH) levels, are good indicators for prognosis. We retrospectively analyzed the prognostic factors of our patients with ENKL. Patients and methods: A total of forty-two patients were diagnosed as having ENKL from April 1998 to May 2011 at Yokohama City University Hematology Group, consisting of eight hospitals in Japan. Central pathological review was not performed; only the individual institutional diagnoses were used. Overall survival (OS) was measured from the date of diagnosis to the date of death or the last follow-up. This study was approved by the Yokohama City University Hospital Clinical Research Ethics Board. The procedures used in this study were in accordance with the Helsinki Declaration. Results: The study included 27 males and 15 females, with the median age at diagnosis of 63 years (range, 18–82 years). Twenty-five patients had localized while 17 patients had advanced Ann Arbor stages of lymphoma. Thirty-two patients had a good ECOG performance status of 0–1. B symptoms were present in 18 patients. Thirty patients presented with nasal and/or paranasal lesions. Twelve patients showed no nasal/paranasal involvement. Of these patients, seven (7/12) had skin involvement, and one each (1/12) with involvement of the gingiva, liver, intestines, testis and lymph node, respectively. According to IPI, 17 patients were classified as low, 9 as low-intermediate, 6 as high-intermediate (HI), and 10 as high (H) risk. According to PIT, 10 patients were categorized as group 1, 16 as group 2, 10 as group 3, and 6 as group 4. According to the Korean index, 11 patients were classified as group 1, 9 as group 2, 10 as group 3, and 12 as group 4. Combined radiotherapy-chemotherapy was administered to 23 patients, 11 patients were treated with chemotherapy alone, 6 patients received radiotherapy alone, and two could not be treated due to their poor condition. After a median follow-up duration among all patients of 12 months (range 1–93 months), and a median follow-up duration among patients still alive at their last follow-up of 47 months (range 8–93 months), 3-year OS rate was 46.7%. Factors associated with a worse overall survival in a univariate analysis were IPI score of HI or H (p<0.001), PIT group 3 or 4 (p=0.002), Korean index group 3 or 4 (p=0.003), extranasal disease (p=0.01), advanced Ann Arbor stage (stage III or IV, p<0.001), ferritin levels higher than 300 ng/ml (p=0.001), B symptoms (p=0.001), albumin levels less than 4 g/dl (p=0.003), LDH value at normal levels or above (p=0.005), soluble IL2R levels higher than 650 U/ml (p=0.006) and β2 microglobulin levels higher than 2.5 mg/l (p=0.035). Multivariate analysis revealed three factors: advanced stage (III or IV) (HR 8.994; 95%CI, 2.188–36.963, p=0.002), extranasal disease (HR 4.824; 95%CI, 1.400–16.624, p=0.013), and high ferritin levels (HR 18.767; 95%CI, 4.207–83.724, p<0.001), to be significant and independent prognostic factors. Conclusion: Advanced stage, extranasal ENKL, and high ferritin levels were associated with an adverse outcome for patients with ENKL. The former two were demonstrated as prognostic factors in previous reports. As far as we are concerned, this is first report showing ferritin levels as a prognostic factor. This result should be confirmed in a large number of cases. Disclosures: No relevant conflicts of interest to declare.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9567-9567
Author(s):  
Victor T Chang ◽  
Charles B. Scott ◽  
Jan Einhorn ◽  
Houling Yan ◽  
Melanie L. Gonzalez ◽  
...  

9567 Background: A Recursive Partitioning Analysis (RPA) algorithm predicted four groups with distinct median survivals in patients with advanced cancer entering palliative care (ASCO 2010, Abst 9040). We investigated whether this algorithm could apply to cancer patients starting systemic therapy. Methods: The RPA algorithm is based upon Karnofsky performance status (KPS), Functional Assessment of Cancer Therapy (FACT) physical well-being (PWB) subscale, and Memorial Symptom Assessment Scale Short Form (MSAS-SF) physical symptom distress (PHYS) subscale. Starting in 2007, a convenience sample of Veterans who were prescribed systemic treatment for their cancer was enrolled in an IRB approved protocol, and completed quality of life (FACT- G) and symptom (MSAS SF) questionnaires prior to starting the first cycle of treatment. We analyzed records of patients with stage IV metastatic solid tumors enrolled through August 2011, and determined survival as of December 1, 2012. Analyses were performed with STATA 11.0. Results: There were 72 patients (pts). The median age was 63 yrs, (range 46-86). Men comprised 71 (98%) pts. First line systemic therapy was given to 59 (82%) pts. The most common primary sites were lung cancer (25 pts, 35%), prostate 9 pts(12%) and colon 7 pts (10%). Median KPS was 90% (range 40-100%), PWB median 23 (range 6-28), and MSAS SF median PHYS 0.73 (range 0-2.93). Overall median survival was 269 days (range 6-1762) and 57 pts (79%) had died. There was 1 pt in group 1, 45 pts in group 2, 8 pts in group 3, and 18 pts in group 4. Median survival (days) by RPA group was 155 for group 1, 177 for group 2, 292 for group 3, and 610 for group 4 (p=.011). Conclusions: These preliminary findings suggest that this algorithm is capable of dividing patients with metastatic solid tumor who are starting chemotherapy into prognostic groups. It may have applications in clinical trials. Further development is indicated. [Table: see text]


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15578-e15578
Author(s):  
Hyehyun Jeong ◽  
Yeonghak Bang ◽  
Hyeon-Su Im ◽  
Jihoon Kang ◽  
Dok Hyun Yoon ◽  
...  

e15578 Background: Although dCRT is the standard treatment for pts who have locally advanced unresectable EC or refuse surgery, the prognosis of these pts remains dismal. There are urgent needs to develop the novel treatment strategy based on prognostic stratification after dCRT. Methods: A total of 382 pts with locoregional EC without distant metastasis except for supraclavicular lymph node who received dCRT at Asan Medical Center in South Korea from 2006 to 2015 were included. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier method. Risk factors were analyzed using Cox regression. Risk scores were calculated by multiplying coefficients in Cox proportional hazard model. Results: Baseline characteristics were as follows: median age = 66 yrs (range: 40-85); male = 359 pts (94.0%); squamous cell carcinoma = 375 (98.2%); cTNM stage (AJCC 8th) I = 40 (10.5%), II = 122 (31.9%), III = 128 (33.5%), IV = 92 (24.1%). During median follow-up of 52.9 mo, median PFS was 13.5 mo (95% CI, 10.9-16.1), and median OS was 26.7 mo (95% CI, 19.8-33.7). In the univariate analyses, sex (only for PFS), weight loss (≥ 5 kg) during dCRT, cT stage, cN stage, cTNM stage, clinical response after dCRT, reason for dCRT were significant prognostic factors for PFS and OS. In the multivariate analyses, clinical response after dCRT, cTNM stage, and weight loss were independent prognostic factors for PFS and OS (Table). Risk-scoring model using these factors stratified pts into four groups: for median PFS (p < 0.0001), group 1 = 58.2 mo (95% CI, 43.5-73.0), group 2 = 17.0 mo (95% CI, 11.9-22.1), group 3 = 9.0 mo (95% CI, 7.0-11.1), and group 4 = 3.9 mo (95% CI, 3.7-4.2); for median OS (p < 0.0001), group 1 = 106.2 mo (95% CI, 44.9-167.6), group 2 = 38.0 mo (95% CI, 24.4-51.5), group 3 = 13.0 mo (95% CI, 8.5-17.6), and group 4 = 8.0 mo (95% CI, 7.4-8.6). Conclusions: In dCRT-treated locoregional EC pts, survival outcome significantly varied according to baseline clinical stage, treatment response, and dynamic change in body weight. Different treatment and surveillance strategies based on the risk score might be needed in these pts.[Table: see text]


2020 ◽  
Vol 15 (2) ◽  
pp. 50-57
Author(s):  
Bassam M Flamerz Arkawazi

Background: Treatment of invasive prolactinoma, which has several characteristics including invasive growth into cavernous sinuses and formation of giant adenomas compressing adjacent neural structures, resulting in neurological dysfunction, has been very challenging. There are relatively few reports available describing long-term treatment outcome. Aims of the study: In this study we evaluate the results of cabergoline administration as initial treatment during 4 years follow up period. Methods: We prospectively categorized 36 patients into four groups according to the results of 3 months of cabergoline treatment: group 1, tumor volume reduction (TVR) ˃25% with normalized serum prolactin (NP) (n = 24); group 2, TVR˃25% without NP (n = 4); group 3, TVR ˂25% with NP (n = 5); and group 4, TVR ˂25% without NP (n = 3). Results: During follow-up, 22 patients (91.7%) in group 1 achieved TVR˃50% with NP. Three patients (75%) in group 2 achieved TVR˃50% with NP after treatment for 8 months. In group 3, four patients (80.0%) continued medication because of improvement of symptoms and achieved additional TVR(18.8–46.4%). Surgery was performed on five patients (one in group 2, one in group 3, and three in group 4), and complete resection was achieved in four (80.0%). Overall, 25 (69.4%) of the 36 patients treated with cabergoline had complete response and 6 (16.7%) had partial response but did not require surgery. Thus, the overall response rate was 86%,with only five patients (14%) requiring surgical debulking. NP was not achieved by surgery alone in all cases, even after total resection of tumor. Conclusion: Patients who achieve TVR˃25%with NP with 3 months of cabergoline administration had a high possibility of showing good long term response (TVR˃50% with NP) to cabergoline. A higher dose of dopamine agonist (DA)  should be considered for patients who achieve TVR˃25% without NP.


VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


2019 ◽  
Vol 17 (4) ◽  
pp. 354-364
Author(s):  
Hassan Al-Thani ◽  
Moamena El-Matbouly ◽  
Maryam Al-Sulaiti ◽  
Noora Al-Thani ◽  
Mohammad Asim ◽  
...  

Background: We hypothesized that perioperative HbA1c influenced the pattern and outcomes of Lower Extremity Amputation (LEA). Methods: A retrospective analysis was conducted for all patients who underwent LEA between 2000 and 2013. Patients were categorized into 5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2 (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (≥9.5%)]. We identified 848 patients with LEA; perioperative HbA1c levels were available in 547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and 13.6%, respectively. Results: The overall mortality was 36.5%; of that one quarter occurred during the index hospitalization. Mortality was higher in Group 1 (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively, p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and 5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after adjustment for age and sex but was statistically insignificant. The rate of LEA was greater among poor glycemic control patients; however, the mortality was higher among patients with tight control. Conclusion: The effects of HbA1c on the immediate and long-term LEA outcomes and its therapeutic implications need further investigation.


2021 ◽  
pp. 197140092098356
Author(s):  
Marwan Alkrenawi ◽  
Michael Osherov ◽  
Azaria Simonovich ◽  
Jonathan Droujin ◽  
Ron Milo ◽  
...  

Background Cervical discopathy and demyelinating lesions often co-exist in patients with multiple sclerosis (MS). Our study examines the possible association between these two pathologies. Methods Medical records and cervical magnetic resonance imaging scans of MS patients with cervical discopathy who were seen at our MS clinic during 2018 were retrospectively reviewed. The severity of the disc disease was classified as grade I (no compression), grade II (compression of the dural sac) and grade III (cord compression). The spinal cord in each scan was divided into six segments corresponding to the intervertebral space of the spine (C1–C6). Each segment was defined as containing demyelinating lesion and disc pathology (group 1), demyelinating lesion without disc pathology (group 2), disc pathology without demyelinating lesion (group 3) and no demyelinating lesion or disc pathology (group 4). Fisher’s exact test was used to test the association between demyelinating lesions and disc pathology. Results Thirty-four MS patients with cervical discopathy were included in the study (26 females; average age 42.9 ± 13.7 years; average disease duration 8.4 ± 5.4 years). A total of 204 spinal cord segments were evaluated. Twenty-four segments were classified as group 1, 27 segments as group 2, 52 segments as group 3 and 101 segments as group 4. There was no association between demyelinating lesions and the grade of disc disease ( p = 0.1 for grade I, p = 0.3 for grade II and p = 1 for grade III disc disease). Conclusion Our study did not find any association between cervical disc disease and demyelinating spinal cord lesion.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Wanyu Zhang ◽  
Yihong Guo

AbstractOestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles. The data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels ≤ 1000 pg/mL, n = 230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n = 524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n = 783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n = 548 ), and group 6 (serum E2 levels > 5000 pg/mL, n = 852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors. The LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), 2.9% (group 5), and 2.0% (group 6) (P = 0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET. The results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF. Although this study provides some reference, the obstetric-related factors were not included due to historical reasons. The impact of the high estrogen environment during COS on the birth weight of IVF offspring still needs future research.


Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 133-146 ◽  
Author(s):  
Sophie Louvet-Vallée ◽  
Irina Kolotuev ◽  
Benjamin Podbilewicz ◽  
Marie-Anne Félix

Abstract To compare vulva development mechanisms in the nematode Oscheius sp. 1 to those known in Caenorhabditis elegans, we performed a genetic screen for vulva mutants in Oscheius sp. 1 CEW1. Here we present one large category of mutations that we call cov, which affect the specification of the Pn.p ventral epidermal cells along the antero-posterior axis. The Pn.p cells are numbered from 1 to 12 from anterior to posterior. In wild-type Oscheius sp. 1 CEW1, the P(4-8).p cells are competent to form the vulva and the progeny of P(5-7).p actually form the vulva, with the descendants of P6.p adopting a central vulval fate. Among the 17 mutations (defining 13 genes) that we characterize here, group 1 mutations completely or partially abolish P(4-8).p competence, and this correlates with early fusion of the Pn.p cells to the epidermal syncytium. In this group, we found a putative null mutation in the lin-39 HOM-C homolog, the associated phenotype of which could be weakly mimicked by injection of a morpholino against Osp1-lin-39 in the mother’s germ line. Using cell ablation in a partially penetrant competence mutant, we show that vulval competence is partially controlled by a gonadal signal. Most other mutants found in the screen display phenotypes unknown in C. elegans. Group 2 mutants show a partial penetrance of Pn.p competence loss and an abnormal centering of the vulva on P5.p, suggesting that these two processes are coregulated by the same pathway in Oscheius sp. 1. Group 3 mutants display an enlarged competence group that includes P3.p, thus demonstrating the existence of a specific mechanism inhibiting P3.p competence. Group 4 mutants display an abnormal centering of the vulval pattern on P7.p and suggest that a specific mechanism centers the vulval pattern on a single Pn.p cell.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Cristina Chimenti ◽  
Romina Verardo ◽  
Andrea Frustaci

Abstract Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p < 0.0001, Sperman r 0,95). Hypertrophy of unaffected myocytes appear to concur to progression and severity of FDCM. It is likely a paracrine role from neighboring affected myocytes.


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