bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Factors and Outcomes of Patients with Acute Myeloid Leukemia (AML) Receiving Non Intensive Chemotherapy (NIC) or Best Supportive Care (BSC).
Authors: Baz Rachid , Rodriguez Cristina , Jawde Rony Abou , Rybicki Lisa , Kalaycio Matt , Advani Anjali , Sobecks Ronald , Sekeres Mikkael A. 
Published: April 2020

Abstract
Background: AML in older adults poses therapeutic challenges, as many patients are not candidates for intensive chemotherapy (IC), and it is not clear that IC provides a survival benefit compared to NIC/BSC. While risk factors and outcomes of patients treated with IC are well-defined, few data support similar prognostication in patients treated with NIC or BSC.
Methods: We conducted a retrospective review of all patients with AML receiving NIC or BSC at the Cleveland Clinic between January 1997 and December 2005. NIC consisted of treatment with hydroxyurea, low-dose cytarabine, or azacitidine. The choice and decision of therapy was dictated by patient and physician preferences. Data on known prognostic factors (age, white blood cell count (WBC) at diagnosis, cytogenetic risk groups (as defined by CALGB 8461) and AML etiology (de novo vs. secondary AML)) were collected and controlled for in multivariable analyses, and survival determined using the log-rank test, measured from the time of diagnosis. Race and residential zipcodes were obtained from information disclosed by patients in their electronic medical records. Average annual household income in a zipcode was obtained using a web-based database, www.melissadata.com.
Results: Fifty-three patients were identified. The median age was 74 years (range 33–92), and 26 patients (49%) were female. Eight patients (15%) were African American (AA), while 44 patients were Caucasian (C) and 1 patient was neither AA nor C. The median WBC at presentation was 6.0 ×103/μL. Cytogenetics were favorable in 1 patient (2%), intermediate in 10 (19%), unfavorable in 19 (36%), and unknown in 23 (43%). Most patients (60%) had secondary AML. The median average annual income was $39,332 (range 23,375–82,806). The median survival was 54 days (95% CI 33–80 days) for all patients, and the 1 year survival was 7%. Known prognostic factors for AML (WBC at presentation, de novo vs. secondary AML, cytogenetics, and age at diagnosis) were not predictors of overall survival in multivariable analyses in patients not receiving intensive chemotherapy, though higher WBC count was predictive in univariable analyses. Race was a predictor for outcomes, with AA patients experiencing a worse median survival than their C counterparts (22 days versus 64 days, log rank p=0.03, figure 1) despite similar baseline characteristics. SES, however, had no impact on outcome.
Conclusions: AML patients receiving NIC or BSC have a median survival of almost 8 weeks, with AA patients experiencing worse outcomes. A small but significant percentage of patients remain alive at one year. Prognostic variables useful in treatment decision-making in patients receiving IC are less valuable for NIC/BSC patients. This information can be used for patient counseling and to help guide treatment decisions.
Figure Figure
Mechanism Study of HL-60 Leukemic Cells Proliferative Inhibition Induced by Chinese Medicinal Herbs Mixture Jieduweikang Pill.
Authors: Zhang Ri , Wu Pin , Zhu Zi-ling , Cen Jiannong , Wu De Pei 
Published: April 2020

Abstract
Background. It’s not surprising that the traditional Chinese herbal remedy is yielding useful drug leads. The mixture composed of thirteen Chinese medicinal plants---jieduweikang(JDWK) pill including Qingdai, Qinghao, Huangchi, Baihuasheshecao, Banzhilian and so on has been shown the clinical antitumor effects in China. We here report the mechanism investigation of JDWK pill cytotoxicity to leukemia cell line HL-60.
Methods By using the method of serum pharmacology, the serum containing the JDWK pill was collected from rats. The MTT and tumor colony formation were used to determine the effects of JDWK pill on proliferation of HL-60 cells. NBT reduction, DNA electrophoresis, flow cytometry and RT-PCR were used to analyze the differentiation and apoptosis of HL-60 cells after treating with JDWK pill. Elisa was used to assay the secretion of VEGF from HL-60 cells.
Results The liquid growth and colony formation of HL-60 cells were evidently inhibited by the serum containing JDWK pill and the cells were shown characteristic DNA “ladder” on agarose gel electrophoresis and more than 20% apoptotic cells in DNA histogram as well as the downregulation of bcl-2 gene related to apoptosis in a concentration-dependent manner, compared with the control. NBT reduction assay indicated that JDWK pill with low concentration may induce myeloid terminal differentiation of HL-60 cells and the level of VEGF was obviously decresed.
Conclusion The JDWK pill can exerts the its anti-proliferative effect on the leukemic HL-60 cells through inducing apoptosis relating to the downregulation of Bcl-2 gene and anti-angiogenic effects with higher concentration and inducing myeloid differentiation with lower concentration.
Extramedullary Infiltrates of AML: Biological and Clinical Features in a Single Centre Experience.
Authors: Carluccio Paola , Pastore Domenico , Liso Arcangelo , Albano Francesco , Mestice Anna , Giannoccaro Margherita , Santodirocco Michele , Mongelli Patrizia , Manduzio Palma , Specchia Giorgina , Liso Vincenzo 
Published: April 2020

Abstract
Extramedullary infiltration (EMI) of malignant myeloid precursor cells in acute myeloid leukemia (AML) may occasionally be a presenting clinical symptom at onset and may develop at any site in the body but most commonly in the gum, skin, central nervous system (CNS) and soft tissue. There is controversy about the prognostic significance of extramedullary disease in AML. The present study examines the incidence, the biological features and prognostic significance of EMI at diagnosis in adult patients with AML. From January 1997 to December 2004, 213 untreated patients with de novo AML were studied. According to Grimwade et al, 14 patients were in the favorable-risk group, 159 in the intermediate-risk group, 25 in the poor risk group and in 15 the karyotype was not available. All patients had been treated with induction therapy according to the GIMEMA protocols including cytarabine, etoposide and idarubicin (15 pts), or mitoxantrone (15 pts) or daunorubicin (183 pts).
Of 213 cases with de novo AML, 29 (14%) had EMI at diagnosis. Ten patients (34.8%) had skin infiltrates, 12 (41.4%) had gum hypertrophy, 5 (17.2%) had CNS involvement and 2 (6.9%) had soft tissue infiltration. No significant differences in terms of sex, age median Hb level and platelets count were found between patients with EMI and patients without EMI. The patients with EMI had higher median WBC counts (27 × 109/L) than patients without EMI (8.5 × 109/L) (p=0.05). The patients with EMI had a higher incidence of the M4/M5 FAB subtype (62%) than patients without EMI (27.4%) (p=0.005). Cytogenetic analysis was performed in patients with and without EMI; none of the abnormal cytogenetic findings was associated with EMI. We evaluated the relationship between the AML blasts surface antigen expression and EMI; the association between CD56/CD4 and CD56/CD14 was more significantly expressed in patients with EMI (35% and 29%, respectively) than without EMI (10.4% and 6.9%, respectively) (p=0.004, p=0.003).
The overall CR rate was 65%; the CR rate was lower in patients with EMI (48.2%) than patients without EMI (76.1%) (p=0.001) and their disease free survival was also shorter (p=0.017); the median duration of CR was 10 and 25 months (range 2–96) in EMI and no EMI group, respectively.
Our data show that a high WBC count, M4/M5 subtype, CD56/CD4 and CD56/CD14 expression are associated with extramedullary infiltrates of AML at diagnosis; the presence of EMI adversely affects the complete response rate to induction chemotherapy and the OS rate. Analysis of the clinical and biologic features in a larger series of adult AML patients is needed to evaluate the allocation of this subgroup in a different or more intensive treatment arm.
Effective Treatment of Biphenotypic Acute Leukemia in Children with Chemotherapy Alone.
Authors: Al-Seraihy Amal S. , Ayas Mouhab , Owaidah Tarek , El-Solh Hassan , Al-Mahr Mohammed , Al-Musa Abdulrahman , Al-Saleh Mahasen S. , Al-Ahmari Ali , Belgaumi Asim F. 
Published: April 2020

Abstract
Biphenotypic acute leukemia (BAL) is now a well-defined entity. However, the outcome of this rare type of acute leukemia is variable and the treatment strategies are controversial. This is a retrospective review analyzing the clinical features and the outcome of BAL cases diagnosed and treated at our institution between January 1999 and December 2004. The diagnosis was based on morphological and cytochemical evaluation, supported with extensive immunophenotyping. The European Group for Immunophenotyping in Leukemia (EGIL) scoring system was utilized to diagnose the BAL. 17 patients (4.1% of 411 ALL patients) were classified as BAL. Of these 15 were B-lymphoid/myeloid and two were T/B-lymphoid. Median age at diagnosis was 7.23 years (range 1.3–14.4 years). Nine patients were male, four had WBC count &gt;100 × 109/L, and 6 (35.3%) had CNS disease. Cytogenetic analysis was available in 14 cases of which three (21.4 %) had a normal karyotype. The most frequent abnormalities were MLL gene rearrangement (n=4; 28.6%) followed by abnormality at the 14q32 locus (n=3; 21.4%; two patients with add(14)(q32) and one t(8:14)(q21:q32)). All patients were treated uniformly, on a modified St Jude TXIII-B high-risk protocol, with agents known to be effective against both lymphoid and myeloid leukemia. They received a 6-drug induction with prednisone, vincristine, daunomycin, asparaginase, etoposide and cytosine arabinoside, followed by consolidation using high-dose methotrexate (2gm/m2) and mercaptopurine. Post remission all patients were eligible for allogeneic bone marrow transplantation (BMT) if a full matched related donor was available. If none was available, patients received continuation therapy consisting of weekly administration of non cross-resistant drug pairs for 120 weeks. All patient achieved remission post induction. Five patients underwent BMT in first remission (CR1), and 12 were treated with chemotherapy (CTX) alone. Two patients in the CTX arm relapsed. Both relapses were extramedullary (isolated CNS in one and lacrimal duct in the other). These patients were reinduced and underwent BMT in CR2. There were no relapses in the BMT arm. No serious acute therapy-related toxicity or infections were noted in the CTX arm. One patient died of BMT- related complications in CR1. With a median follow-up of 2.6 years, the actuarial OS and EFS at 4 years are 71.6 % and 79.5%, respectively. OS and EFS comparing BMT with CTX are 82% v. 74.1% (p=0.5) and 80% v. 79.5% (p=0.84), respectively. We conclude that this chemotherapy protocol is effective and safe in treating BAL. BMT in CR1 may not be needed for these patients.
Incidence of Venothromboembolism (VTE) in Patients (pts) with Acute Lymphocytic Leukemia (ALL), Burkitt’s Leukemia/Lymphoma (BL) or Lymphoblastic Leukemia (LL).
Authors: Vu Khanh D. , Thomas Deborah A. , Hubbard Julie C. , Faderl Stefan , Cortes Jorge , Cabanillas Maria E. , Garcia-Manero Guillermo , O’Brien Susan M. , Kantarjian Hagop 
Published: April 2020

Abstract
Background: Pts with cancer are at increased risk of thromboembolic events with potentially life-threatening consequences. The incidence of VTE in cancer pts has been estimated at 1 in 250. Although most of these episodes are associated with solid tumors, VTE is also observed in pts with acute leukemias, even in the presence of thrombocytopenia. Anticoagulation in this pt population can be particularly problematic if pts are undergoing myelosuppressive chemotherapy. VTE prophylaxis is often not given because of the perceived high risk of bleeding with a presumed low risk of VTE.
Method: As little is known about the incidence and significance of VTE in pts with acute leukemia, we conducted a retrospective chart review of 223 pts with ALL, BL, or LL who received a hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) with or without rituximab, maintenance chemotherapy (with L-asparaginase only months #7 & 18), allogeneic stem cell transplant (SCT), or salvage chemotherapy at our institution from November 1999 to May 2005. The median observation period was 112 weeks (range 1–328).
Results: The median age was 51 yrs (range 19–75). 70% were ALL, (50% were Philadelphia positive ALL), 20% Burkitt’s or Burkitt’s-like, and 10% LL. Thirty nine of 223 pts (18%) had confirmed VTE by imaging studies: 12.5% prior to or at the time of diagnosis, 57.5% during consolidation chemotherapy, and 27.5% during maintenance chemotherapy, SCT, or supportive care. Location of VTE varied by site: 3/39 (8%) pulmonary embolus, 16/39 (41%) lower extremity, 2/39 (5%) central venous catheter (CVC), and 18/39 (46%) upper extremity. Two of the 18 with upper extremity VTEs did not have CVC, and an additional 2 had bilateral upper extremity thromboses. The platelet counts were reviewed near the time of VTE diagnosis: 22/39 (56%) had greater than 100 × 109/L, 17/39 (44%) were less than that value, with 76% below 50,000 × 109/L.
Conclusion: Pts with ALL, BL, and LL undergoing therapy are at risk for developing VTE. Thrombocytopenia does not preclude development of VTE. A more detailed analysis will be forthcoming regarding the risk factors for VTE in this pt population, the current medical practices and bleeding complications with VTE prophylaxis and treatment, and the effect on therapy administration and overall survival. Practice guidelines for management of acute leukemia pts with thromboembolic events should be pursued.
Phase I Trial of Sphingosomal Vincristine (SV, Marqibo®) and Dexamethasone in Relapsed or Refractory Acute Lymphocytic Leukemia (ALL).
Authors: Thomas Deborah A. , Kantarjian Hagop M. , Heffner Leonard , Stock Wendy , Garcia-Manero Guillermo , Faderl Stefan , Ferrajoli Alessandra , Giles Francis , Wierda William , Ravandi-Kashani Farhad , Choy Gavin , Berk Gregory I. , O’Brien Susan 
Published: April 2020

Abstract
Delivery of standard therapeutics in formulations which allow increased drug delivery with equivalent or less toxicity may improve outcome. Vincristine is an essential component of ALL therapy. Its cytotoxicity occurs in a time and dose-dependent manner, but the dose needs to be capped at 2 mg to prevent severe neurotoxicity. SV is a form of vincristine encapsulated in sphingomyelin liposomes or “sphingosomes” with an increased circulation half-life of 12 hours compared with 6–12 minutes for free vincristine. In vivo, SV has more anti-tumor activity than free vincristine in mice bearing P388 and L1210 leukemias. A previous study of single agent SV 2.0 mg/m2 given every 2 weeks (without dose capping) was conducted in 16 patients (pts) with relapsed or refractory ALL. Objective responses were observed in 14% (1 complete response [CR], 1 partial response [PR]); 36% had transient reduction in marrow leukemia infiltrate with very minimal toxicity (Thomas et al., Cancer106:1641, 2006). An increase in dose intensity was considered the strategy for future trials. A standard 3 + 3 phase I study of weekly escalating doses of SV (1.5 mg/m2, 1.825 mg/m2, 2 mg/m2, 2.25 mg/m2, 2.4 mg/m2) with pulse dexamethasone (D) 40 mg daily days 1–4 and 11–14 was initiated. Pts with active grade 2 or greater central or peripheral neuropathy (PN) were excluded. Pts were evaluated for dose-limiting toxicities (DLT) after 1 course (defined as 4 weekly doses of SV + D). To date, 36 pts with relapsed/refractory ALL were enrolled. Median age was 34 years (range, 21–62). Median number of prior salvage regimens was 2 (range, 1–3); all pts had prior vincristine. SV was discontinued early for progressive disease (n=5), death due to sepsis (n=3) or other toxicities (n=3). Thus, twenty-five pts (71%) completed 1 full course and were considered evaluable. DLTs were observed at the 2.4 mg/m2 dose level (grade 3 PN, seizure with intracranial hemorrhage, grade 4 hepatotoxicity). The tentative MTD is 2.25 mg/m2 (expansion of cohort ongoing). Expected toxicities included infections related to neutropenia, grade 1–3 constipation, grade 1–2 PN and transient grade 1–3 elevations in hepatic transaminases related to azole antifungal prophylaxis. Six pts (24%) achieved CR (2 at 1.5 mg/m2, 1 at 1.825 mg/m2, 2 at 2.25 mg/m2, 1 at 2.4 mg/m2), 1 a PR (at 2.25 mg/m2), and 3 (12%) hematological improvements (of platelets at 1.825 mg/m2 and 2 mg/m2 or clearance of marrow blasts at 2.25 mg/m2). Five responders proceeded to allogeneic stem cell transplant. In conclusion, SV with pulse dexamethasone demonstrated encouraging activity in relapsed or refractory ALL. Phase II and III studies of SV in ALL are planned.
Bevacizumab Reduces VEGF Expression in Patients with Relapsed and/or Refractory Acute Myeloid Leukaemia (AML) without Clinical Antileukemic Activity.
Authors: Zahiragic Lejla , Schliemann Christoph , Bieker Ralf , Berdel Wolfgang E. , Mesters Rolf M. 
Published: April 2020

Abstract
Angiogenesis is required for tumor growth and metastasis and is an attractive target for cancer therapy. Because of its pivotal role in tumorassociated angiogenesis across a wide range of malignancies, vascular endothelial growth factor-A (VEGF-A) has emerged as a central therapeutic target in cancer.
Neoangiogenesis has been shown to play an important role in the pathogenesis of AML (Padro et al., Blood 2000) and antiangiogenic therapy could constitute a novel strategy for its treatment (Mesters et al., Blood 2001). Autocrine and paracrine secretion of vascular endothelial growth factor (VEGF) in the bone marrow may promote proliferation and survival of leukemic blasts (Fiedler et al., Blood 1997). This concept represented the rationale for the therapeutic application of bevacizumab (BV), a recombinant humanised monoclonal antibody against VEGF, in patients with advanced AML after failure of standard treatment. Nine patients (median age 63 years; range 46–81 years) with relapsed and/or refractory AML not judged medically fit for further intensive chemotherapy were enrolled in this study. All patients received at least one cycle of BV (10 mg/kg body weight), 5 patients received 2 cycles (days 1 and 14) and 2 patients a 3rd cycle (day 35). Treatment was well tolerated, without treatment-related side effects. Two patients had to be withdrawn from drug administration after cycle one due to progressive disease. After treatment with BV none of the patients fulfilled the criteria of a partial response, defined as the clearance of at least 50 % marrow blasts accompanied by increases in platelet counts and haemoglobin values. The level of VEGF expression in the bone marrow determined by immunohistochemistry significantly decreased during treatment with BV (before BV treatment: median of 3.78 arbitrary units (AU) [range 1.5–5.8 AU]; after BV treatment: median of 2.57 AU [range 1.3–5.0 AU]; Wilcoxon test, P&lt;0.05). In contrast, VEGFR-2 expression by leukemic blasts and bone marrow microvessel density did not change significantly. In conclusion, single agent BV has no significant antileukemic activity in relapsed and/or refractory AML.
Compassionate Use of Intrathecal Depot Cytarabine (DepoCyte®) in Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML): Report of 11 Cases.
Authors: Sancho Juan-Manuel , Parker Anne , Deben Guillermo , Bolam Simon , Gimenez Eugenio , Sanchez-Garcia Eva , Piñana Jose-Luis , Pascual Teresa , Mateos Carmen , Fernandez-Abellan Pascual , Palomera Luis , Ribera Josep-Maria 
Published: April 2020

Abstract
Treatment of CNS involvement in patients with AML is based on repetead intrathecal (IT) administrations of chemotherapy, especially methotrexate and cytarabine, until to achieve clearance of blast cells from cerebrospinal fluid (CSF). Recently, the availability of a depot formulation of liposomal cytarabine (DepoCyte®), administered every two weeks by IT route, has demonstrated to be useful for the treatment of neoplastic and lymphomatous meningitis. However, there are few studies that have analyzed its efficacy in the prophylaxis and treatment of CNS involvement in patients with AML. A retrospective review was performed of all cases in which IT depot cytarabine was employed as compassionate therapy for CNS involvement of AML in Spain and United Kingdom. From March 2004 to April 2006, 11 AML cases (2 with acute promyelocytic leukemia [APL]) were recorded. The median (range) age was 46 (18–57) yr and there were 7 females. Six patients had CNS involvement at the time of the diagnosis and the remaining had CNS relapse (first CNS relapse in 4, 2nd relapse in 1). Four out of 6 patients with initial involvement received IT depot cytarabine after one dose of triple IT therapy (TIT) administered during the screening lumbar puncture (one patient received two TIT doses), another received cranial irradiation in addition to IT depot cytarabine, and the remaining was treated only with IT depot cytarabine. The 5 patients with CNS relapse received one TIT dose plus IT depot cytarabine in 3 cases, cranial irradiation plus IT depot cytarabine in one, and only IT depot cytarabine in the remaining. Complete resolution of neurological symptoms was observed in 9 cases and partial response in the remaining 2, whereas clearance of blasts from CSF was observed in 7 evaluable cases. Sustained response was observed in 6 patients (median follow-up 6 [4–23] months) whereas the remaining 5 died from infection (3) or systemic relapse (2), without evidence of neurological progression. The median number of IT depot cytarabine administrations was 3 (1–10). Concurrent dexamethasone therapy (4 mg twice/day/5 days) was administered with each dose of IT depot cytarabine. Side effects included headache (3 patients), fever (1) vomiting (1) and nausea (1). Depot formulation of cytarabine was effective to obtain clearance of blasts cells from CSF in AML patients with CNS involvement or relapse. The administration of depot formulation of cytarabine was well tolerated. This justifies the development of a clinical trial to evaluate the efficacy and safety of IT depot cytarabine in meningeal involvement of AML.