bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Chronic Myelogenous Leukemia in Iran
Authors: Keyhani Manoutchehr , Charoussae Ramezan , Toogheh Gholamreza 
Published: April 2020

Abstract
Treatment of chronic myelogenous leukaemia has been revolutionized during the past ten years all over the world. Even though Iran is oil producing nation. The government contribution to health is a low percentage of general income. According to Iranian law all drugs should be generics if generic is available. For this reason and imatinib production by India the only drug available to Iranian with chronic myelogenous leukaemia through insurance is Indian imatinib. The cost is one tenth of the original Gleevec brand and with general public Insurance all patient could afford the medicine. We have evaluated 3 years response to this generic drugs in Iran. In this cohort study from 1992 –2008 in the Imam Khomeini hospital, Shraiati hospital and Arad hospital the total of 303 patients were studied. 233 patients on imatinib treatment. The median age of Iranian Patient with CML were 40 years and it is 10 years less than other studies.. This disease is more common in the male than female in Iran. The primary response at presentation was 96.2% and 3.8% had no response. Finally the 3 years disease free survival had been 84.2%. In 1st year and 2nd year some patient progressed to blastic and accelerating phase while in the 3rd year very few developed accelerated phase. Kaplan-Meier 1-year disease free survival = 92.3% (SE=1.8) 2-year disease free survival = 88.0% (SE=2.3) 3-year disease free survival = 84.6% (SE=2.6)\
Conclusion: Generic Imatinib is as effective as original and very inexpensive. This kind of medicine should be available to every afflicted patient all over the world.
A Retrospective Study of Introferon-Alpha Treatment on Chinese Patients with Chronic Myeloid Leukemia
Authors: Yan Hua , Shen Zhi-Xiang 
Published: April 2020

Abstract
Introduction: Chronic Myeloid Leukemia (CML) is one of the myeloproliferative malignancies characterized by the reciprocal t(9;22)(q34;q11) chromosome, which causes the generation of Bcr-Abl fusion protein. Interferon-alpha (IFN-alpha) was introduced into clinical application from 1980s’ and showed its treatment benefit mainly in chronic phase CML (CML-CP) patients including achieving hematological remission, prolonging survival. Our retrospective study aimed to evaluate its clinical efficacy as well as toxicities in Chinese CML-CP patients.
Methods: This is a retrospective, multicentric clinical trial. Chinese CML patients in chronic phase received IFN-alpha treatment from 1992 to 2006 were enrolled. Other agents such as hydroxyurea or cytarabine treatment were permitted during treatment excepted for tyrosine protein kinase inhibitors.
Results: 1037 CML-CP patients were into analysis, the median age was 42 yrs (range 9–80) and male: female ratio of 1.6:1. The median time for interferon treatment was 12 months (range from 1 month to 136 months). 86.32% of patients received 300Mu of interferon, three times a week, 10.88% in 300Mu of daily injection, while another 2.8% in 500Mu of interferon treatment, three times a week. Main of additional treatment included hydroxyurea, which was used in 8.9% of patients, and cytarabine treatment in 3.3% of patients. We evaluate the best response reaction during IFN-alpha treatment, 496 out of 1037 patients obtained hematological remission (47.8%). 33 in complete cytogenetic remission (CCR, 3.2%) but unfortunately 60% of them were lost CCR after median of 6–11 months; 89 in partial cytogenetic remission (8.6%); 40 in major cytogenetic remission (3.9%); 301 in minor cytogenetic remission (29%); 78(7.5%) of CML-CP patients worsen into accelerate phase or blast crisis. Non-Hematological toxicities during IFN-alpha treatment mainly included flu-like symptom (24.9%) and fatigue (23.5%) which were transient and most of patients got recovery after second injection whereas 20% of them could not endurable. While hematological toxicities were neutropenia (22.1%, 33% of them were in grade III or IV), and thrombocytopemia (16.9%, 33% of them in grade III or IV).
Conclusion: The IFNalpha is one candidate agent for CML-CP patients in China with moderate toxicities during treatment, but it has little influence on achieving or maintaining complete cytogenetic remission.
Phase II Explorative Study of Intermittent Imatinib (IM) Treatment (INTERIM) in Elderly Patients with Ph+ Chronic Myeloid Leukemia (CML) Who Achieved a Stable Complete Cytogenetic Response (CCgR) with Standard IM Therapy
Authors: Russo Domenico , Malagola Michele , Colombi Chiara , Breccia Massimo , Fogli Miriam , Galieni Piero , Martinelli Giovanni , Mirto Salvatore , Vitolo Umberto , Abruzzese Elisabetta , Alimena Giuliana , Bocchia Monica , Carella Angelo Michele , Pane Fabrizio , Rosti Gianantonio , Saglio Giuseppe , Specchia Giorgina , Baccarani Michele 
Published: April 2020

Abstract
Standard therapy with Imatinib (i.e. daily administration) significantly prolongs the survival of Ph+ CML patients who obtain a complete cytogenetic response (CCgR). Elderly patients (i.e. &gt; 65 yrs) have similar cytogenetic responses and survival, but they usually show a low compliance. This prospective multicenter trial addresses the issue of intermittent administration of Imatinib (INTERIM) in Ph+ CML patients older than 65 years with stable complete cytogenetic response (CCgR) after at least 2 years of standard therapy with IM. Lower doses of IM could be sufficient to maintain the CCgR, to improve the tolerance and to reduce the costs of therapy. For this purpose, IM will be given at the same dose that was given at the time of enrollment by the following intermittent schedule: 1 week on/1 week off for the 1st month (weeks 1–4); 2 weeks on/2 weeks off for the 2nd and 3rd month (weeks 5–12); 1 month on/1 month off from the 4th month thereafter (weeks 13 on). The primary objective of the study is to evaluate the proportion of patients who remain in CCgR with INTERIM. The cytogenetic response (CgR) status will be evaluated at baseline (by conventional cytogenetics on bone marrow and FISH on peripheral-blood) and every 3 months during the study (only by FISH on peripheral-blood). If FISH documents a variation of the baseline value of more than 1% in two consecutive examinations, evaluation of marrow cells metaphases will be performed to confirm the loss of CCgR and to check for additional cytogenetic abnormalities (ACA). In case of loss of CCgR INTERIM will be stopped and standard therapy (daily administration) will be resumed. Quantitative molecular assessment of BCR-ABL transcript by RQ-PCR on peripheral blood is due at baseline and every 3 months during the study and mutational analysis of ABL will be performed in case of loss of CCgR. After 12 months, the patients who are in continuous CCgR are advised to continue the intermittent study schedule and to be followed indefinitely. The study started in May 2008 and, at present, 18 patients have been enrolled. Preliminary data on the first six months will be presented.
Treatment of Chronic Myeloid Leukemia with Imatinib. A Single Centre Experience
Authors: Parente Anna , Sureda Anna , Aventin Anna , Brunet Salut , Martino Rodrigo , Briones Javier , Valcarcel David , Delgado Julio , Nomdedeu Josep , Sierra Jordi 
Published: April 2020

Abstract
With the introduction of imatinib (IM) as first-line therapy for chronic myeloid leukemia (CML) as well as in advanced phases of the disease, the long-term outcome of this hematologic malignancy has dramatically changed.. The aim of this study has been to analyse the experience of our centre with IM therapy in CML patients, focusing on the cytogenetic and molecular responses according to the phase of the disease in which IM was given, as well as the treatment failures and the results of the mutational analysis performed in these situations. Between January 2000 and March 2008, 77 patients with CML [47 men and 30 women, median age 49 years (range, 18–78)] were treated with IM. 33 of them received IM at a dose of 400 mg qd as first-line treatment in de novo chronic-phase (CP), 32 patients received it in late chronic-phase [time from diagnosis to IM, 51 (12–157) months]. Of these 32 patients in late CP, all of them received prior therapy with interferon-alpha, 10 patients received an autologous transplant and 3 of them an allogeneic transplant. Five patients were initially treated with IM 600mg qd because of an accelerate-phase (AP) and the remaining 6 patients were treated with IM 800mg qd because of a blastic-phase (BP).
De novo CP Late CP AP BC CHR(%) 32 (96) 28 (87) 4 (80) 3 (50) Time to CHR in months [median (range)] 1,8 (0,5–6) 1 (3–10) 2 (0,5-4) 3 (1–5) CCR(%) 30 (90) 22 (68) 3 (60) 1 (17) Tims to CCR in months [median (range)] 11 (6–63) 10 (6–36) 12 (7–18) — MMoIR(%) 20 (60) 15 (47) 1 (20) 1 (17) Time to MMoIR in months [median (range)] 18 (6–68) 22 (6–58) — — CMoIR(%) 0 0 0 0 Time to CMoIR in months [median (range)] — — — — Relapses (%) 5 (15) 9 (28) 4 (80) 5 (87) Mutational analysis (n, %) 4 (80) 6 (66) 3 (75) 3 (50)     Positive 2 (50) 2 (33) 1 (33) 0     Negative 2 (50) 4 (67) 2 (67) 3 (100) Second-line treatment     Dasatinib 1 3 0 1     Allo-SCT 1 2 0 1     Others — 3 3 — Follow-up from diagnosis 41 (11–90) 103 (34–215) 107 (37–185) 74 (13–158) Follow-up from beginning of IM 43 (11–97) 52 (6–87) 52 (13–83) 22 (1–88)     Alive 31(94) 22(69) 3(60) 2(33)     Death 2(6) 10(31) 2(40) 4(67)
The results of our centre confirm the ones presented in prospective analysis. There is a small percentage of patients that relapse or progress under IM therapy, and this percentage is significantly higher in patients treated in advanced phases. Mutational analysis is relevant in up 50% of the patients studied, allowing changes in therapy according to the obtained results.
Multivarite Analysis of Risk Factors for Affected Patients Long-Term Persistent Survival after Allogeneic Hematopoietic Cell Transplantation
Authors: Ding Jia-hua , Yu Zhengping , Chen Bao-an , Li Yu-feng , Ding Bang-he , Qian Jun , Cao Xiang-shan 
Published: April 2020

Abstract
Objective To analysis the risk factors for affected patients the long-term persistent survival in 96 patients undergoing Allogeneic Hematopoietic Stem Cell Transplantation, in order to take active prevention and cure measure, and improve trans- plantation curative effect preferably.
Methods We retrospectively analysis 96 cases of patients subject to allo-HSCT. The 11 clinical parameters were selected for univariat -e analysis using a Cox regression:age, sex, morbid state, HLA locus, donor type, donor -recipient blood type, conditioning regimen, aGVHD, HC, VOD, IP. Factors that were significant at the 0.1 level on univariate analysis were evaluated by multivariate an- alysis using a Cox regression. The cumulative incidence of aGVHD and patients survival rate were calculated by the method of Kaplan and Meier.
Results ninty-five patients achieved sustained donor engraftment except one patients not. The median time of leukocyte engraftment was 13 days. The incidence rates of grades I~IV acute GVHD was 43.75%. grades III~‡WaGVHD was 12.50%. Ten patients relapsed and 38 dead, the overall survival at 5 years was 60.42%. The COX method analysis showed that aGVHD and diease states at transplant were significantly risk factors to improved overall survivals(OS), with relative risk [RR] 2.996 and 2.619, respectively.
Conclusion aGVHD and diease states at transplant had significantly improved OS, the key to improvement the outcome 0f allo-HSCT is to reduce the incidence and severity of aGVHD, meanwhile selecting the suitable opportunity for transplantation. We had better do HSCT in CR1to treat that patients with advance refractory and recurrence.
Impact of Chronic Graft Versus Host Disease Over First Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemias and Chronic Myeloid Leukemia
Authors: de Sousa Eulalio Emmerson , Schulz Elizabeth , de Oliveira José Salvador Rodrigues 
Published: April 2020

Abstract
Hematopoietic stem cell transplantation (HSCT) has been a potential curative treatment for hematological malignancies. Graft versus host disease (GVHD) produces the graft versus leukemia (GVL) effect, an immunologic response capable to protect the HSCT recipient against cancer cells. Chronic GVHD (C-GVHD) is one relevant cause of mortality and remains a hazard in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to investigate the influence of the GVL effect associated with the C-GVHD over the disease free survival in patients with acute leukemias (AL) and chronic myeloid leukemia (CML). We studied a retrospective cohort of 192 patients with AL (n=77) and CML (n=115) aged 14–62 years (median 32) who underwent allo-HSCT with identical HLA donors in the Hospitals Sao Paulo and Santa Marcelina, in Sao Paulo, Brazil, from August 1993 to December 2004. We used in our study the criteria of C-GVHD of Seattle cited by Shulman et al (1995) revised by Lee (2003). The C-GVHD incidence was 78.4% (76/97) and 66.7% (36/54) in CML and AL, respectively. First relapse in CML occurred in 14.5% (11/76) of the cases with C-GVHD and in 61.9% (13/21) of the cases without C-GVHD. This fact shows the striking negative correlation and impact between the GVL effect and the incidence of first relapse post allo- HSCT in CML. The clinical severity of C-GVHD influenced significantly and inversely the chance of first relapse, once CML patients with extensive C-GVHD (2/45) had a lower relapse rate than limited disease (9/31) (4.4% versus 29%; p = 0,003). Subdividing CML patients in two groups, early (CML-Chronic Phase, CP) and advanced disease (CML-Accelerated Phase/Blastic Crisis, AP/BC), the first relapse rate was also correlated with the severity of C-GVHD. Relapse rates were 64.3% (9/14), 27.3% (6/22), and 5.6% (2/36) in CML-CP patients with absent, limited, and extensive C-GVHD (p = 0.0001), and 57.1% (4/7), 33.3% (6/9), and 0.0% (0/9) in CML-AP/BC, respectively (p = 0.037). Similarly, AL patients with C-GVHD showed a relapse rate of 27.8% (10/36) compared with 83.3% (15/18) when C-GVHD was absent (P = 0.0001). When we analyzed AL patients by stage of disease at transplantation (early AL patients: in first CR; advanced AL patients: after first relapse or refractory) with and without C-GVHD, patients with early AML (17/29) or early ALL (11/25) had a lower relapse rate than patients with more advanced AL (AML: 23.5% versus 66.7%; p = 0.02; ALL: 18.2% versus 78.6%; p = 0.003). Hence, the presence of C-GVHD in our cohort of AL and CML patients was an important determinant capable of modifying the outcome in these pathologies. The clinical severity of the C-GVHD was the most relevant factor to determine a lower relapse rate in CML patients, despite the stage of disease at time of transplantation.
Pre-Transplant Comorbidity as An Outcome Predictor in Hematopoietic Cell Transplantation for Severe Aplastic Anemia
Authors: Lim Sung-Nam , Lee Je-Hwan , Lee Jung-Hee , Kim Dae-Young , Kim Se-Hyung , Lee Young-Shin , Kang Young-A , Seol Miee , Kang Sol-Ip , Ryu Seong-Gil , Lee Kyoo-Hyung 
Published: April 2020

Abstract
A new hematopoietic cell transplantation specific comorbidity index (HCT-CI), which was modeled to effectively capture comorbidity and predict post-transplant outcomes, has been evaluated in a cohort of patients with a variety of hematologic disorders. In this study, we applied the HCT-CI to 77 patients with severe aplastic anemia who underwent HCT at the Asan Medical Center, Seoul, Korea between February 1995 and September 2007. Pre-transplant HCT-CI score was calculated in each patient using the clinico-pathologic data, which were retrieved from Asan Medical Center Bone Marrow Transplantation Registry Database. HCT-CI score was 0 in 54 patients (70%), 1 in 16 (21%), 2 in four (5%), and 4 in one (1%). The most prevalent comorbidity captured by the HCT-CI was infection (n=11) followed by arrhythmia (n=6). During a median follow-up period of 54.4 months (range, 4.0 to 159.0 months), 19 patients died and 16 experienced primary or secondary graft failure. The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 73.4% and 63.3%, respectively. OS and EFS were significantly different according to HCT-CI score; OS 86.6% and EFS 74.3% in patients with score 0 versus 43.5% and 38.5% in those with score 1 or more (P&lt;0.001 for OS and P=0.001 for EFS). Other significant prognostic factors for OS were age (&lt;30 years vs. ≥30, 90.8% vs. 58.3%, P=.002), pre-transplant transfusion amount (&lt;50 units vs. ≥50, 93.0% vs. 61.0%; P=.005) and time from diagnosis to HCT (&lt;120 days vs. ≥120, 85.2% vs. 61.4%; P=.013), and prognostic factors for EFS were age (&lt;30 years vs. ≥30, 81.0% vs. 48.4%, P=.003) and time from diagnosis to HCT (&lt;120 days vs. ≥120, 77.4% vs. 48.3%; P=.007). Multivariate analysis after adjustment for other variables demonstrated that HCT-CI score (HR 10.022, P&lt;.001 for OS; HR 4.644, P&lt;.001 for EFS), age (HR 8.447, P=.002 for OS; HR 4.060, P=.003 for EFS), time from diagnosis to HCT (HR 5.783, P=.002 for OS; HR 3.956, P=.002 for EFS) were independently significant prognostic factors for both OS and EFS. In conclusion, our data indicate that the presence of pre-transplant comorbidity assessed by HCT-CI may predict worse outcomes after HCT in severe aplastic anemia.
Cystatin C Level as a Marker of Renal Function in Hematopoietic Stem Cell Transplantation
Authors: Muto Hideharu , Ohashi Kazuteru , Ando Minoru , Hanajiri Ryo , Kikuchi Taku , Munakata Wataru , Sakurai Chihiro , Yamamoto Masahide , Kobayashi Takeshi , Yamashita Takuya , Akiyama Hideki , Sakamaki Hisashi 
Published: April 2020

Abstract
Hematopoietic stem cell transplantation (HSCT) recipients have an increased risk of acute kidney injury (AKI) or chronic kidney disease (CKD). However, serum creatinine level may underestimate the prevalence of these renal complications because of decreased lean body mass or concurrent liver disease, which was frequently observed in a HSCT setting. Cystatin C measurement may be more sensitive for detecting impaired kidney function. We retrospectively reviewed the medical records of 70 HSCT (54 allogeneic and 16 autologous) recipients who had at least one chance to monitor serum cystatin C level during last 2 years in our institution, and evaluated cystatin C as a possible new marker which can predict subsequent renal dysfunction. The occurrence of AKI was defined by the RIFLE classification and CKD staging was based on KDOQI criteria. Of 70 transplant recipients, 20 patients developed AKI after median 50.5 days (range 0–283 days) after HSCT, while worsening CKD stage was observed in 21 patients during observational periods. Cystatin C level was not influenced by pretransplant disease status (P=0.153) or autologous transplant (P=0.311), but significantly elevated after allogeneic transplantation (P&lt;0.001). Multivariate analysis disclosed that the use of calcineurin inhibitor was a major cause of cystatin C elevation (Odds ratio 7.00, P=0.045). There was also a strong inverse correlation between cystatin C and estimated GFR (r=−0.684, P&lt;0.001). Proportional hazard modeling analysis revealed that pretransplant cystatin C level (&gt;0.90mg/l) and the episode of AKI after transplantation were a great risk for substantially worsening CKD stage (Hazard ratio 4.21 and 16.0, P=0.042 and P&lt;0.001, respectively). Cystatin C measurement could be a useful clinical tool to identify HSCT recipient at increased risk for CKD.
Identification of Acute Lymphocytic Leukemia Extramedullary Relapse and PTLD after Allo-HSCT by FISH Monitoring Sex Chromosome Chimeric Status
Authors: Du Xuan , Liu Qifa , Zhang Leshi , Song Lanlin , Fan Zhiping , Xu Bing , Sun Jing 
Published: April 2020

Abstract
Objectives : To explore the role of fluorescence in situ hybridization (FISH) monitoring sex chromosome chimeric status in the identification of leukemic extramedullary relapse and post-transplant lymphoproliferative disease (PTLD) in acute lymphocytic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods: Six ALL patients who received sex-mismatched allo-HSCT manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrow (BM) were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization (ISH).
Results: The sex chromosomes in BM of all 6 patients were 100% donor-derived. Among the sex chromosome chimeric status of tumor tissues, those of three patients were mainly recipient-derived, and the percentage of sex chromosomes derived from recipients were 100%, 100% and 98.0%, respectively, and then they were diagnosed leukemic extramedullary relapse. And those of the other 3 patients were donor-derived, the percentage was 98.5%, 96.0% and 91.5%, respectively, and diagnosed PTLD. EBV-RNA and latent membrane protein (LMP-1) were positive in 2 patients with PTLD and negative in the other 4 patients. One patient with extramedullary relapse obtained partial remission, one with PTLD gained complete remission, and the others died eventually after therapy.
Conclusion: Monitoring the sex chromosome chimeric status by FISH is an effective method to distinguish leukemic extramedullary relapse from PTLD in ALL received sex-mismatched donor HSCT.
Second Allogeneic Stem Cell Transplantation as Treatment for Chronic Myeloid Leukemia Relapse Following a First Reduced Intensity Conditioning Allograft
Authors: Benakli Malek , Hamladji Rose-Marie , Ahmednacer Redhouane , Talbi Amina , Mehdid Farih , Belhadj Rachida , Baazizi Mounira , Rahmoune Nadia , Harieche Farida , Zerhouni Fatiha 
Published: April 2020

Abstract
Background: Relapsed chronic myeloid leukemia (CML) is a possible complication after allogeneic stem cells transplantation (SCT). Treatment options for relapse include chemotherapy, Donor lymphocyte Infusion (DLI) and second SCT. In such treatments, second SCT is the only potentially curative therapy. We report the results of myeloablative transplantation as second SCT in 7 adults patients (pts) with CML relapsed after first reduced intensity conditioning (RIC) allo-SCT.
Patients and methods: Between April 2001 and December 2006, 154 CML pts treated with RIC allo-SCT from an HLA-identical family donor. First RIC-SCT following conditioning using Fludarabine 150 mg/m2 and oral Busulfan 8 mg/m2. GVHD prophylaxis consisted of association Ciclosporine and Mycophenolate (6 pts), one patient received an additional prophylaxis with ATG. Twenty four pts (16%) relapsed, of whom 7 underwent second conventional allograft. The median time between first and second SCT was 11 (range, 3–24) months. As second SCT, the median age was 34 (range, 23–46) years and gender: 3 male, 4 female. Six pts were in second chronic phase and one pt in accelerated phase. In all cases, myeloablative conditioning consisted of Busulfan (8 mg/kg), Etoposide (30 mg/kg) and Cyclophosphamid (120 mg/kg). Second SCT used with another HLA-identical sibling donor in 4 cases. All received G-CSF mobilized peripheral blood stem cells, with median CD34+: 5,85 106/kg (range,3,28–9,34). GVHD prophylaxis was consisted of Ciclosporine-Methotrexate.
Results: All pts had myeloid reconstitution and the median time to achieve 0,5 109/l neutrophils count was 25 (range,15–57) days. One pt needed a boost 40 days after allograft. The median time of aplasia was 20 (range,10–52) days. No acute GVHD noticed. Four pts had chronic GVHD, of whom 3 with extensive form. Although 3 pts died of relapse on 2, 3 and 20 months. Four pts are alive and free of disease on 24, 48, 55 and 55 months respectively after second SCT with complete chimerism of donor origin and negative minimal residual disease, of whom 3 had second allo-SCT with another family donor.
Conclusion: This study suggests that second SCT for CML relapse after RIC-SCT can result in long-term survival for some of pts without lethal treatment related toxicity. Another HLA-identical sibling donor is favourite in this case. Further follow-up and more pts are necessary to validate this series.