bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Risk for Venous Thromboembolism in Patients with Acute Leukemia.
Authors: Mohren Martin , Markmann Ilka , Jentsch-Ullrich Kathleen , Koenigsmann Michael , Lutze Gerd , Franke Astrid 
Published: October 2019

Abstract
Introduction: Patients with solid tumors have an increased risk for venous thromboembolisms (VTE) associated with substantial morbidity and mortality, but so far there exists little data on hematologic malignancies. We have recently found a VTE rate of 7,7% in patients with malignant lymphoma. However, information on patients with acute leukemia (AL) is very limited so far.
Patients and methods: Medical records of all patients with AL treated in our institution between january 1992 and april 2005 were reviewed and data was collected and analyzed in a microsoft excel data base. P-values to show correlation of VTE with leukemia type, patient age and gender were calculated using Fisher’s exact test. All reported p-values are two-sided.
Results: Of a total of 455 patients 310 (68%) had AML, 108 (24%) had ALL and 37 (8%) had blast crisis. 248 patients (55%) were male and 207 (45%) were female, median age was 60 years. 55 patients with AL (12,1%) had at least one VTE, occuring during therapy in 82% of events. 27 patients (5,9%) had central venous catheter associated VTE, whereas 28 patients (6,2%) had deep vein thrombosis and/or pulmonary embolism. Neither leukemia lineage - myeloid versus lymphocytic - (p=1,0) nor patient gender (p=.193) had an impact on the VTE risk. However, central venous catheter associated VTE more likely occured in younger patients (< 60 years) than in patients ≥ 60 years (p=.003). There was no statistically significant difference in the incidence of non-central venous catheter associated VTE between both age groups (p=.563).
Discussion: Patients with acute leukemia have a substantial risk for VTE, half of which occur with the use of central venous catheters. A recently published study analysed the incidence of VTE in close temporal relationship to onset of disease and found a VTE rate of 2,09% with equal risk in ALL and AML. Our study included VTE occuring prior to diagnosis of AL as well as during chemotherapy and follow up, revealing a VTE rate that is 6-fold higher and showing a considerable association with central venous catheters.
Conclusions: The risk of VTE is surprisingly high in patients with acute leukemia, thus improvement of prophylactic measures, especially in regard to central venous catheter use is warranted.
Longitudinal Assessment of Inflammatory Cytokines and Symptom Severity during 100 Days of Allogeneic BMT for AML/MDS Patients.
Authors: Wang Xin S. , Cleeland Charles S. , Williams Lori , Reuben James , Lee Bang-Ning , Mobley Gary , Giralt Sergio 
Published: October 2019

Abstract
BMT patients develop multiple symptoms At nadir after transplantation that include pain, fatigue, poor appetite, and disturbed sleep. Animal models of sickness behavior suggest such symptoms may be related to increases in inflammatory cytokines. The objective of this study was to prospectively assess the relationship between symptom severity and changes in inflammatory cytokines.
Methods: Weekly symptom assessment with the M. D. Anderson Symptom Inventory was done for 30 AML/MDS patients during the first 100 days of Allo-BMT. A panel of inflammatory cytokines (IL-1ra, IL-6, IL-8, IL-10, IL-12, TNF-a) was assayed at several time points: pre BMT, conditioning, BMT day, BMT Day1, nadir, BMT day14, 21, 28, 60, 90–100.
Results: Multiple symptoms peaked at nadir, with some symptoms (fatigue and pain) remaining at high levels after nadir. Figure 1 shows the Lowess curves for selected symptoms on MDASI. Physical symptoms had much larger fluctuation than affective symptoms during the study. Figure 2 presents Lowess curves of the serum levels of cytokines (log base 10). IL-6 and IL-8 showed significant increase during nadir, significantly correlating with fatigue, lack of appetite, drowsiness, dry month, and feeling physically sick (all P<.01).
Conclusion: There is an observed relationship between increased symptom severity levels and increased inflammatory cytokine (mainly IL-6 and IL-8) levels during the acute phase of allo-BMT in AML/MDS patients. The question of a causal link between cytokine levels and symptom severity requires further study.
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Gemtuzumab Ozogamicin Combined with Hyper-CVAD in Relapsed Refractory CD33-Positive Acute Lymphoblastic Leukemia.
Authors: Stromberg Olga , Stenke Leif , Bernell Per 
Published: October 2019

Abstract
Adult patients with relapsed or refractory ALL have a dismal clinical prognosis. The CD33 antigen is expressed on leukemic cells of approx 30% of all ALL cases. For such patients, a combination of an anti-CD33 MoAb with chemotherapy may provide an effective therapeutic option, although clinical data are yet scarce. Here we describe our experience using gemtuzumab ozogamicin (Mylotarg), an anti-CD33 antibody linked to calicheamycin, combined with cytostatics as reinduction chemotherapy for two relapsed, refractory CD33-pos ALL patients.
Case 1. A male 32 yr old patient diagnosed with pre-B-ALL in April 2004. He showed no poor-risk criteria at diagnosis but needed two induction courses to enter complete remission (CR). After having received two cycles of consolidation therapy and a maintenance treatment he relapsed in October 2004. He then failed to respond to reinduction chemotherapy with RIEHM AA (Holoxan, Oncovin, Emthexat, Betamethason, Cytarabine, Etoposid) and MEA-Asp (Novantrone, Cytarabine, Etoposid, Asparaginase). As a 3rd reinduction option he was given “hyper-CVAD” (Cyklofosfamid, Oncovin, Doxorubicin, Dexamethason) combined with Mylotarg (6mg/sqm on day 10). The patient then achieved a full CR on day 28 and was scheduled for a subsequent allogeneic transplantation with an unrelated donor. However, due to an extended toxic colitis he was unable to receive consolidation treatment and again relapsed on day 36 after CR. Shortly thereafter the patient died in a septic shock.
Case 2. A 19 yr old female patient was diagnosed with pre-B-ALL without poor-risk criteria in November 2001. After standard induction therapy she achieved CR and received maintenance treatment until May 2002. In May 2003 bone marrow relapse occurred, but she entered a 2nd CR after reinduction chemotherapy and successfully underwent an allogeneic stem cell transplantation from a matched unrelated donor in September 2003. A second relapse occurred in January 2004. The patient then received reinduction with hyper-CVAD combined with Mylotarg, as described above. This resulted in a 3rd CR. Subsequently she received an identical consolidation course followed by DLI in March 2004. She remained in CR until February 2005 when she again relapsed and died in respiratory insufficiency.
Conclusion. The combination of gemtuzumab ozagamicin and hyper-CVAD may provide a logical, feasible and possibly effective therapeutic option for relapsed and refractory CD33-pos ALL patients.
Clinical and Laboratory Study of CAG Regimen in Treating AML Subtypes Hard To Cure.
Authors: Xu Jianmin , Ji Lili 
Published: October 2019

Abstract
Background and objective: Relapse AML, refractory AML, AML in the old and secondary AML are all AML subtypes hard to cure. They characterize in insensitive to chemotherapy agents, short duration of CR(complete remission), easy to relapse.Yamada et al brought forward CAG regimen, which has been proven effective in treating AML subtypes hard to cure. This regimen can treat these AML subtypes with the CR rate at 62%–86%, media survival of 8–17 months. The adverse reaction of CAG regimen is more moderate than that of standard chemotherapy or salvage therapy. Patients’ life quality gets better when they are treated with CAG regimen. The rationale of CAG regimen is as follows:
G-CSF receptors have been reported to be expressed in blastic cells in almost all the patients with AML; CFU-AML can be killed preferentially by prolonged exposure to low dosage of Ara-c in the presence of G-CSF with relative preservation of normal CFU - GM; G-CSF focuses on the precursor of myeloid lineage, the upstream cells are effected slightly; the Acla-mediated cytotoxicity of CFU-AML, which is effective in treating MDR cells, is reported to be enhanced by short-term combination with G-CSF.
There have been few reports published on the mechanism of CAG regimen, especially on the study in vivo. Our study aims to know the process of the CAG regimen functions in vivo by study of clinical use and series of tests.
Methods: Observe the outcome,change of CBC and BM, adverse reaction of 11 AML patients treated with CAG regimen from Jan. 2003 to Apr. 2005. We enrolled 4 patients treated by CAG regimen as study group, 2 patients treated by DA regimen as control group. Mononuclear cells were isolated from heparinized bone marrow samples by Ficoll-Hypaque centrifugation to be conducted morphological observation, livability test, apoptosis index measurement on FCM(PI and Annexin V stain), and clonal culture.
Results:
CAG regimen treats AML by means of inducing AML blastic cells synchronous apoptosis, having little effect on normal myeloid cells. We treat 11 patients of AML subtypes hard to cure with CAG regimen from Jan. 2003 to Apr. 2005. CR rate is 27.27%, OR rate is 72.73%. The adverse reaction is moderate. Given the CAG regimen, the count of peripheral WBC rises at first, decreases to the lowest level afterward, then recovers at last. The peak count of WBC of 3 CR cases occurs later than that of other patients, at d4 or d7. While that of NR patients occurs at d2. Ara-c and Acla-mediated cytotoxity on normal myeloid cells and megakaryocyte can be alleviated by G-CSF, thus CAG has little influence on the productivity of myeloid precursors.
CFU-AML can be killed preferentially by CAG regimen in the presence of G-CSF.
Conclusion: CAG regimen treats AML by means of inducing apoptosis with better prognosis and more moderate adverse reaction. We hypothesize that CAG regimen recruits S phase cells and kills them by inducing apoptosis.
Outcome after Relapse in Childhood Acute Lymphoblastic Leukaemia - Results of a Single Center for a Period of 15 Years.
Authors: Celkan Tiraje , Karaman Serap , Ozkan Alp , Apak Hilmi , Canpolat Aylin , Yildiz Inci 
Published: October 2019

Abstract
Approximately 25–30 % of children newly diagnosed with acute lymphoblastic leukemia (ALL) will eventually experience leukemic relapse. Bone marrow is the most common site of recurrence. Usually achieving a durable second remission is complicated by toxicity and resistance of the disease. Here we documented our patients in order to see the prognosis of relapsed pediatric ALL cases.
RESULTS. From August 1990 to August 2005 children diagnosed with ALL and treated with BFM based protocols in Cerrahpasa Medical Faculty Pediatric Hematology-Oncology Department were enrolled to this study. There were 225 children aged median 6 years( 3 months–18 years) (136 boys/89 girls), 28 % SR, 50 % MR, 22 % HR. The whole group EFS is 72,6 % and RFI 81,8 %. Twenty-nine (12,8 %) patients were relapsed. Bone marrow recurrences were isolated in 19 patients, and combined with an extramedullary site in 8 patients (4 CNS, 2 testis, 1 retinal,1 dermal). Only two patients had isolated extramedullary site (testis) relapse. The median time to recurrence was 23 months (range 4–128 months). Five patients refused a secondary treatment. Of 24 chemotherapy given patients, 6 patients were lost just after induction therapy due to toxicity before a reliable remission evaluation was done. In three early relapses a second remission could not be attained. Twenty-one patients (72.4 %) achieved a second remission (median length, 4 months; range, 1–114 months)( mean16 ± 80 months). The 5-year survival probability among all patients was 27.2 % ± 8.2 %. Of 8 surviving patients, 3 are in remission more than 5 years, 3 are in remission 2–5 years of period and only 2 less than 1 year. One patient who relapsed for second time is in 3th remission for 65 months period. Bone marrow transplantation was the done for only 3 patients, one is very newly done, the other two relapsed after engrafmant and were lost.
CONCLUSIONS. Despite acceptable long-term second EFS rates for a minor group of patients, childhood ALL recurrences signal a poor outcome being the problem of childhood ALL therapy.
Efficacy and Safety of Fludarabine Combined with Cytarabine in the Treatment of Patients with Relapsed and Refractory Acute Lymphoblastic Leukemia (ALL).
Authors: Jiang Bin , Wang Wei , Bao Li , Huang Xiaojun , Lu Jin , Wang Debing , Lu Daopei 
Published: October 2019

Abstract
Objective: The objective of this study was to evaluate the efficacy and safety of fludarabine (Flu) combined with cytarabine (Ara-c) in the treatment of relapsed and refractory ALL.
Methods: From March 2003 to February 2005, 28 patients in our institution with adult relapsed and refractory acute lymphoblastic leukemia were treated with Flu and Ara-c chemotherapy. The median age of patients was 28 years (range, 11–64 years). Twenty-four patients were treated with Flu IV Ara-c: Flu (30 mg/m2/day as a 30 minute infusion IV dl-4) and Ara-c (1000 mg/m2 ql2h, 6–10 times IV). The Ara-c infusions commenced 4 hours after the fludarabine infusion. Four patients were treated with following regimen: Flu (30 mg/m2/day as a 30 minute infusion IV dl-4), Ara-c (100 mg/day q12h 6–10 times), and mitoxantrone (4 mg/d dl~4 IV).
Results: Efficacy: The overall response rate was 48.1%. Ten of the 27 ALL patients achieved a CR (37%), and 3 patients achieved a PR (11.1%). Median CR duration was 8 months (ranges, 2–34 months). Among 14 Ph- ALL patients, 4 achieved a CR (28.6%); of 8 Ph+ ALL patients, 5 (62.5%) achieved a CR, 2 achieved a PR, and 1 was NR. Among 5 patients with T-ALL, only 1 achieved a CR. The patients with acute mixed lineage leukemia achieved a CR. Among 19 patients with full immunophenotyping data, there were 3 CRs, 1 PR in the 5 ALL patients with myeloid antigens (My+), and 3 CR and 2 PR in 14 ALL patients without myeloid antigens (My−). Four Ph+ My+ ALL patients achieved a CR. Safety: Flu combined with Ara-c resulted in myelosuppression in all patients, 27 patients had WBC <1′109/L, and the median time to WBC <1′109/L was 11 days (range, 5–27 days). The lowest PMN emerged 9 days (range, 3–18 days) after the regimen commenced. Twenty-five patients had PLT <20′109/L, and the median duration was 8 days (range, 1–30 days). The lowest PLT count occurred 11 days (range, 3–18 days) after the regimen commenced. Sixteen patients had pyrexia with 8 definite pathogenic bacterium, 3 bacterial infections, 1 CMV infection, 2 fungal infections, and 2 multiplicity of infection. The major nonhematologic toxicity was gastrointestinal symptoms (35.7%, 10/28), such as nausea, vomiting, diarrhea, anorexia (i.e. WHO grade 1 or 2), and the symptoms disappeared soon after the regimen completed.
Conclusion: Favorable efficacy and safety were obtained in relapsed and refractory ALL patients treated with Flu and Ara-c, especially in Ph+ ALL and My+ ALL patients. In the future, larger studies are warranted to evaluate the efficacy and safety of Flu and Ara-c.
Acute Leukemia in Patients Sixty Years of Age and Older: A Retrospective Review.
Authors: Leger Chantal S. , Lee Ann , Leitch Heather A. , Galbraith Paul F. , Li Charles H. , Vickars Linda M. 
Published: October 2019

Abstract
Acute leukemia, especially acute myeloid leukemia (AML), occurs more frequently in the elderly population. Treatment outcomes for this condition have traditionally been poor and very few patients survive for prolonged periods following diagnosis. We performed a retrospective chart review of all patients sixty years of age and older diagnosed with acute leukemia at St. Paul’s hospital, Vancouver, Canada, from June 1984 to July 2004. One hundred and three patients were diagnosed with acute leukemia [AML- 81; ALL- 15; ALN (acute leukemia not otherwise specified)- 7]. The median age was 72 (range 60–88) years. Fifty-seven (55%) and 46 (45%) patients had de novo and secondary leukemia, respectively. Sixteen patients (28%) had an unfavourable karyotype. Fifty-three patients (51%) received induction chemotherapy (treated) and 50 (49%) were provided with supportive care only (untreated). Treated patients were younger [67 years (60–79)] than untreated patients [76 years (61–88)], (p<0.0001), and no patients >/= 80 years were treated (n=17). Of the treated patients, 33 (62%) achieved a complete remission (CR), 10 (19%) had resistant disease and 10 (19%) died from complications related to treatment. The median overall survival for the entire group was 103 (1–1229) days, and for treated versus untreated patients was 216 (1–1213) and 38 (2–1229) days, respectively (p=0.0021). The disease free survival in treated patients achieving a CR (n=33) was 262 days (9–722). Less than 5% of patients were alive at 4 years from diagnosis. Univariate variables predictive of prolonged survival included receiving induction chemotherapy (p=0.0027), de novo as opposed to secondary leukemia (p=0.0420), and younger age, with a relative increase in death in older subgroups (60–69, 70–79, 80+), (p=0.0311). Induction chemotherapy was the only independent predictor of prolonged survival in multivariate analysis (p=0.0027). There was no statistically significant difference in the number of treated patients and treatment outcomes between 1984–1993 and 1994–2004. In conclusion, this single-institution series of 103 patients aged sixty years and older with acute leukemia, shows that the prognosis of this disease in older patients is extremely poor. Even though induction chemotherapy seems to prolong survival in patients who are fit to receive treatment, the prognosis remains grim and most patients ultimately die of leukemia, supporting a role for investigational regimens focusing solely on this age group. It is no longer appropriate to follow regimens that have remained largely unsuccessful and unchanged over 20 years.
Transgene Deletions in Long-Term Circulating Donor Gene-Modified T Lymphocytes Infused at Time of Hematopoietic Transplantation.
Authors: Mercier Patricia , Deschamps Marina , Ferrand Christophe , Robinet Eric , Certoux Jean-Marie , Sauce Delphine , Lioure Bruno , Deconinck Eric , Tiberghien Pierre 
Published: October 2019

Abstract
A phase I/II trial of Herpes-Simplex Virus-thymidine kinase (HSV-tk)-expressing gene modified T cells (GMTC) administration at time of HLA-identical sibling bone marrow transplantation (BMT) demonstrated that such an approach could modulate deleterious alloreactivity after BMT (Tiberghien et al., Blood 2001). The Neomycin resistance gene (NeoR) was transferred together with the HSV-tk gene in a retroviral vector to allow for in vitro GMTC selection. More than 6 years after BMT, 4 patients are alive in complete remission, off immunosuppression, free of chronic graft-versus-host disease (GvHD). Long-term circulating GMTC are continuously found in all 4 patients, as assessed by quantitative PCR (QPCR) for NeoR gene (6 years post-BMT: 0.031 +/- 0.017% of PBMC). Unexpectedly, presence of NeoR gene was readily detected by single run PCR whereas a nested PCR was necessary for HSV-tk gene detection. As PCR assays for both genes have a similar sensitivity, this result suggested that deletions may be present in GMTC. For each patient, PBMC were polyclonally activated and expanded before a one week G418-mediated selection. The % of GMTC in the post-selection samples, as assessed of NeoR QPCR, was > 80% in 3 patients while of only 7% in the last patient, thus demonstrating long-term NeoR transgene expression in at least a fraction of circulating GMTC more than 6 years after BMT. Successfully re-selected GMTC were cloned. As expected, most clones (25 out of 26) were found to be NeoR by PCR. In contrast, only 2/26 were HSV-tk+: one clone contained the full length HSV-tk gene while the second contained the ganciclovir (GCV)-resistant truncated form of the HSV-tk gene (Garin et al., Blood 2001). Clones generated from freshly produced-GMTC were found to be both NeoR+ and HSV-tk+ thus demonstrating that such gene deletions did not occur with a significant frequency during the GMTC production nor during the cloning process. We have previously established that an immune response against GMTC occurred in most patients (Mercier et al., ASH 2004). Immune responses were found against both transgenes and predominantly so against HSV-tk. Immuno-selection of initially rare GMTC containing a deleted transgene without expression of immunogenic peptides might significantly contribute to the high proportion of long-term circulating GMTC containing mutated HSV-tk genes. Such deletions within the transgenes most likely explain the coexistence of an immune response against the transgenes and persistent circulating GMTC. Nevertheless, GCV-sensitivity of circulating GMTC and more importantly so, of GvHD during the first 4 months after BMT suggests that the high frequency of the mutated GMTC occurred late enough after BMT to not interfere with GCV-mediated control of GvHD.
Elderly Acute Myeloid Leukemia: A Retrospective Analysis of 89 Cases in China.
Authors: Lu Zesheng , Du Xin , Long Yi , Weng Jianyu , Lin Wei , Huang Zilun 
Published: October 2019

Abstract
Although acute myeloid leukemia (AML) is generally responsive to chemotherapy, most patients with this disease are older than 60 years and have relatively resistant neoplasms. AML in the older patient is distinctive, both biologically and clinically, from that occurring in patients younger than 60. The intrinsic resistance of AML in the older patient is exemplified by the higher incidence of chromosomal abnormalities. Furthermore, blasts obtained in elderly patients with AML are more likely to express proteins that mediate multidrug resistance, such as the p-glycoprotein encoded by the MDR1 gene. A combination of an anthracycline and a cytarabine is the most commonly used induction regimen in acute myeloid leukemia (AML), but most of Chinese older adults with AML didn’t agree with the standard doses of induction therapy. The study is to analysis the attenuated therapy for Chinese older adults. 89cases of newly diagnosed aged over 60 were observed from February 2000 to July 2005, including 50 male and 39 female, media age is 68yr. Patients were accepted attenuated therapy, either mitoxantrone per day on days 1, 2(MA);35 mg/m2 pirarubicin(TA) 7–8mg/m2 idarubicin per day on days 1, 2 (IA). Each patient was given 100mg/m2 cytarabine intravenously per day for 7 days. Total CR rate was 34% after 2 regimens, 2 years survival rate was 12.5%. The CR and 2-year survival rates of acute leukemia in Chinese elderly AML were low. Physicians should be encouraged to offer standard doses of induction therapy.