High-dose Cytosine Arabinoside Research Articles

High Dose Cytosine Arabinoside- Induced Asymptomatic Bradycardia A Rare Case of Concurrent Pneumoretroperitoneum, Pneumomediastinum, Pneumothorax and Subcutaneous Emphysema Seen After Colonoscopy

Coexistence of pneumoretroperitoneum, pneumomediastinum, pneumothorax and subcutaneous emphysema after colonoscopy is a rarely seen condition. We present this rare clinical condition seen after colonoscopy to contribute to the literature. A 62-year-old male patient, who was operated for acute abdomen two years ago, underwent colonoscopy due to colon stenosis. He applied with the complaints of swelling in the neck and subcutaneous swelling in the chest and abdomen after the procedure. Pneumoretroperitoneum, pneumomediastinum and subcutaneous emphysema were detected in the patient In case of subcutaneous emphysema to be seen after colonoscopy, the possibility of pneumomediastinum and pneumothorax should also be considered.

High Dose Cytosine Arabinoside- Induced Asymptomatic Bradycardia

Cytosine Arabinoside (Cytarabine) is commonly used agents in acute myeloid leukemia (AML). Cardiovascular side effects are not common during treatment. We aimed to present asymptomatic bradycardia developed during the first consolidation treatment in a patient with acute myeloid leukemia. A 34-year-old male patient was diagnosed with AML in February. After induction chemotherapy, high dose cytarabine treatment was started at 2x1.5 grams/m² for consolidation treatment. On the 11th day of the treatment, his pulse decreased to 39 beats/min. On the 12th day after the initiation of high dose cytosine arabinoside treatment (6 days after chemotherapy treatment ends), the patient's pulse rate was above 50/min, and there was no bradycardia in the following days. Other causes of other causes of bradycardia were excluded. It was reported that the patient had sinus bradycardia with an ejection fraction of 65% and his heart rate was rhythmic. There are seven patients with acute myeloid leukemia, one patient with acute lymphoblastic leukemia, one patient with non-Hodgkin's lymphoma, and one patient with Hodgkin's lymphoma who reported high dose cytosine arabinoside associated bradycardia. In addition, one patient with acute myeloid leukemia developed bradycardia with low dose cytosine arabinoside. Our case is the 11th case in the literature that develops bradycardia due to cytarabine.

Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China.

Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.

AML-213 Unusual Presentation of Acute Myeloid Leukemia (AML-M2): A Case Report

Acute myeloid leukemia (AML) is rarely presented with thrombocytosis and marked thrombocytosis with a platelet count over 1.0×1012/L is an extremely rare phenomenon. A case of de novo AML with unusual presentation by extreme thrombocytosis. A case report. Hematology Unit at the Oncology Center Mansoura University, Egypt. A 37-year-old male patient with a history of sleeve gastrectomy in 2020, presented with oral mucositis, recurrent abscess, fever, and bilateral axillary lymphadenopathy. Initial complete blood count (CBC) showed a Hb level of 6 g/dL, a platelet count of 1.685×109/L, and a white blood cell (WBC) count of 19×109/L. Diagnosis of de novo AML (FAB-M2 AML) was confirmed by bone marrow aspiration, biopsy, and immunophenotyping. Cytogenetic study showed negative t(8;21)/inv 16/ t(9;22). A molecular study showed positive FLT-3 mutation and negative BCP/ABL1, JAK2, V617F, and CALR exon 9 mutations excluding blast transformation on top of myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS). The patient received induction chemotherapy including a course of 7-day-cytarabine along with 3-day-anthracycline on September 20th, 2021 but the patient was refractory as BMA showed blast cells 75%. The patient started salvage HAM (high-dose cytosine arabinoside and mitoxantrone) + Sorafenib on November 6th, 2021. Again, he could not achieve a response and received FLAG (high-dose cytosine arabinoside, fludarabine, and granulocyte colony-stimulating factors) + Sorafenib on December 18th, 2021, after recovery from COVID-19 infection. To shed light on fact that myeloid neoplasms as MPN, MDS, and de novo AML can share overlapping features. On January 25th, 2022, the last CBC showed a Hb level of 8.4 g/dL, a platelet Count of 395×109/L, and a WBC Count of 2.41×109/L with a differential Neutrophil count of 0.24×109/L. The patient lost follow-up since then. Only a few AML cases have been reported with thrombocytosis. Detailed molecular studies are mandatory to confirm the diagnosis of de novo AML patients with unusual presentation. Careful follow-up of those cases could help in establishing management guidelines for better outcomes as those patients usually have a poor prognosis.

The diagnostic dilemma of idiopathic intracranial hypertension in a child with acute lymphoblastic leukemia: COVID-19 or cytosine arabinoside?

BackgroundIdiopathic intracranial hypertension is a rare neurological condition among children. Its manifestations vary from mild headaches to loss of vision. Although rare, COVID-19 infection and high dose cytosine arabinoside have been reported as risk factors for this neurological disorder. In patients with acute leukemia, idiopathic intracranial hypertension diagnosis is simple, but finding its etiology can be difficult.Case presentationWe report a case of a 9-year-old boy with an ongoing treatment for T-acute lymphoblastic leukemia presenting with persistent headaches and diplopia. A diagnosis of idiopathic intracranial hypertension was retained based on clinical, imaging and laboratory findings. Due to its rarity, we describe its clinical and therapeutic features and highlight the challenging etiological dilemma between COVID-19 infection and high dose cytosine arabinoside administration.ConclusionPersistent headache in a pediatric patient with leukemia can be due to many neurological disorders other than leukemic relapse. Given the improvement of the neurological symptoms after the SARS-CoV-2 PCR negativization and the successful re-introduction of high dose cytosine Arabinoside, the diagnosis of idiopathic intracranial hypertension associated with Covid-19 infection was withheld.

Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol

IntroductionA better long-term quality of life after umbilical cord blood transplantation (CBT) is observed compared with transplants from other alternative donors, whereas graft failure and relapses after CBT are still...

Survival with “7+3” induction and high dose cytosine arabinoside consolidation in pediatric AML; A prospective observational study of real world scenario

Survival with “7+3” induction and high dose cytosine arabinoside consolidation in pediatric AML; A prospective observational study of real world scenario

Acute cerebellar syndrome after high dose cytosine arabinoside treatment: case report

Acute cerebellar syndrome after high dose cytosine arabinoside treatment: case report

The effect of high-dose cytarabine followed by autologous hematopoietic stem cell transplantation on the outcome of patients with mantle cell lymphoma.

The aim of this study was to investigate the influence of high-dose cytosine arabinoside (HDAC)-containing treatments followed by autologous hematopoietic stem cell transplantation on the survival of patients with mantle cell lymphoma. The data of 27 MCL patients who were followed-up between January 2009 and December 2015 were analyzed retrospectively. The median age of the patients was 63 (range, 45-82) with 22 (81.4%) males and 5 (18.6%) females. Eight of 27 patients were treated with HDAC-containing regimens either as induction or salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT). The patients who received HDAC-containing regimen followed by AHSCT were found to have better one-year survival compared to others (p = 0.03). Median follow-up of patient cohort was 27.6 months and median overall survival (OS) was not reached. The probability of one-year OS for all patients was 76.8%. Our findings suggest that HDAC treatment followed by AHSCT seems to provide the best outcome for young-fit patients presenting with mantle cell lymphoma.

Non-Effectiveness of Using RICE Post RDHAP or RDHAP Post RICE after Failure of First Line Salvage Therapy in DLBCL Patients Who Are Eligible for ASCT

Background: The treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL) remains challenging. The use of salvage chemotherapy followed by autologous stem cell transplantation (ASCT) in young and fit patients is considered the standard of care. RDHAP (rituximab, dexamethasone, high dose cytosine arabinoside and cisplatin) and RICE (rituximab, ifosfamide, carboplatin, and etoposide) are the two most commonly used salvage-regimens with comparable efficacy (CORAL study). However, nearly 40% of the patients do no respond to these regimens and subsequently they do not proceed to ASCT. There are no guidelines concerning the choice of a second-line salvage regimen. There are sparse data in the literature concerning the best choice if the first salvage regimen fails. The aim of our study was to investigate the potential role of a second salvage regimen, before intensification, by RICE or RDHAP in patients with DLBCL refractory to the first line salvage therapy by RDHAP or RICE, respectively.Methods: We retrospectively included all patients aged 18 years and above who had a relapsed or refractory DLBCL and who were eligible for an autologous stem cell transplant (ASCT) between the years 2008 and 2017. They should have had progressive or stable disease (PD/SD) following first-line salvage based on RICE (group 1) or RDHAP (group 2) and should have received a second-line salvage based on RDHAP or RICE, respectively. Patients who received carboplatin or oxaliplatin instead of cisplatin in the RDHAP protocol were also included. All cases were discussed at a tumor board and the revised International Working Group response criteria for Malignant lymphoma were used to assess the response to chemotherapy. Information were collected using electronic medical record. Ethics committee approval was not necessary.Results: 100 patients' medical files were reviewed, out of which 69 were excluded for the following reasons: 5 patients lacked necessary information; 13 patients were treated for a non-DLBCL; 30 patients could not receive second line salvage therapy because of deterioration of their performance status; 21 patients because they received a bridging therapy (other than RICE or RDHAP) before second line salvage therapy. The study included 31 patients with 19 (61.3%) males and 12 (38.7%) females. The median age was equal to 59 years (standard deviation 14). DLBCL was at the initial diagnosis in all but 6 patients in whom DLBCL developed after an indolent lymphoma (follicular lymphoma in 4 and marginal zone lymphoma in 2). 70% had germinal centre B-cell subtype, while 30% had activated B-cell subtype. 70% were refractory to the primary therapy (CR not attained on primary therapy or relapsed within 6 months) and 30% recurred after a CR lasting more than 6 months. All patients included in group 1 (n=5) have received cisplatin during the treatment with the RDHAP regimen. Among the 26 patients included in the second group, 19 (73.1%) have received cisplatin, 4 (15.4%) oxaliplatin, and 3 (11.5%) carboplatin in first line salvage. No patient in group 1 responded to RICE and eventually no patient proceeded to ASCT. In the second group, 2 patients (7.7%) deceased after the first cycle of RDHAP because of drug related toxicities (1 due to ifosfamide-induced encephalopathy and 1 due to septic choc following febrile neutropenia). Ten patients (38.5%) responded to RDHAP, in whom an ASCT was planned. However, 2 patients could not proceed to ASCT because of peripheral stem cell collection failure. After a median follow up of 8.7 months, the median progression free survival (PFS) of the 8 patients who proceeded to ASCT was 6.3 months (CI 95% 2.6-10.1). Only 1 patient had a tumor response lasting more than 30 months. No factor was found to be associated with PFS on cox regression analysis (which included age, sex, type of DLBCL, and refractory or recurrent status).Conclusion: There is little information regarding the effectiveness of a second-line salvage therapy in patients not responding to first line intensification. All except one patient either could not proceed to ASCT or had a limited response (less than 3 months) post ASCT. In addition, the toxicity was not negligible considering that 2 patients died because of drug related events. This study suggests that patients with DLBCL who failed to respond to first line salvage by RDHAP or RICE should be considered for investigational therapies rather than second line rescue. DisclosuresRibrag:pharmamar: Other: travel; MSD: Honoraria; BMS: Consultancy, Honoraria, Other: travel; Roche: Honoraria, Other: travel; Amgen: Research Funding; argenX: Research Funding; Servier: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; Incyte Corporation: Consultancy; Gilead: Consultancy, Honoraria; Infinity: Consultancy, Honoraria; epizyme: Consultancy, Honoraria.

Patient Characteristics and Treatment Patterns in the First-Line and Second-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in the United Kingdom, France, and Germany

Introduction: Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are hematologic malignancies with poor prognosis for patients who do not respond well to therapy. As current treatment options may be suboptimal for many patients, it is important to better understand the current treatment landscape for DLBCL and FL. Here we provide recent real-world evidence on patient characteristics and treatment patterns in relapsed/refractory (R/R) DLBCL and R/R FL across the United Kingdom (UK), France (FRA), and Germany (DE).Methods: Hematologists and oncologists (N=140) from the UK, FRA, or DE retrospectively identified patients diagnosed with R/R DLBCL or R/R FL who received at least two lines of therapy and had radiographically or clinically measurable disease with at least one target lesion per International Working Group criteria for malignant lymphoma. Descriptive statistics examined patient characteristics and treatment patterns in first-line (1L) and second-line (2L) therapy.Results: Mean (SD) age at initial diagnosis was 59.9 (10.9) years for the aggregate DLBCL patient sample (N=272). DLBCL patients were primarily male (69.1%), distributed across the UK (29.0%), FRA (36.8%), and DE (34.2%), and had various Eastern Cooperative Oncology Group (ECOG) performance statuses at initial diagnosis (0 ECOG 28.7%, 1 ECOG 48.9%, 2 ECOG 14.3%, ≥3 ECOG 5.9%, unknown ECOG 2.2%).Mean (SD) age at initial diagnosis was 61.0 (10.2) years for the aggregate FL patient sample (N=282). FL patients were primarily male (53.9%), distributed across the UK (29.4%), FRA (36.9%), and DE (33.7%), and had various ECOG performance statuses at initial diagnosis (0 ECOG 30.5%, 1 ECOG 50.7%, 2 ECOG 13.5%, ≥3 ECOG 4.2%, unknown ECOG 1.1%). DLCBL and FL patient characteristics by country are presented in Table 1.DLCBL patients in 1L and 2L received combination regimens (93.8% and 82.7%, respectively) or monotherapy regimens (6.2% and 17.3%, respectively). DLCBL patients in 1L received treatment largely consistent with current guidelines, consisting mainly of systemic therapy only (86.8%) and treatment with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP, 68.0%). DLCBL patients in 2L completed multiple therapy cycles (median 3 cycles) and were treated with systemic therapy only (79.4%), systemic therapy and radiation (4.0%), systemic therapy and stem cell transplantation (SCT, 16.2%), or systemic therapy, radiation, and SCT (0.4%). The most common 2L DLCBL regimens were: rituximab, dexamethasone, high-dose cytosine arabinoside, and cisplatin (R-DHAP, 19.5%); bendamustine plus rituximab (12.9%); rituximab, dexamethasone, cytarabine, and oxaliplatin (R-DHAX, 12.5%).FL patients in 1L and 2L received combination regimens (86.5% and 78.4%, respectively) or monotherapy regimens (13.5% and 21.6%, respectively). FL patients in 1L received treatment largely consistent with current guidelines, consisting mainly of systemic therapy only (90.8%) and treatment with R-CHOP (35.1%). FL patients in 2L completed multiple therapy cycles (median 4 cycles) and were treated with systemic therapy only (90.1%), systemic therapy and radiation (2.1%), systemic therapy and SCT (6.0%), or systemic therapy, radiation, and SCT (1.8%). The most common 2L FL regimens were: bendamustine plus rituximab (33.3%); R-CHOP (9.6%); R-DHAP (8.5%). DLCBL and FL 2L treatment patterns by country are presented in Table 2.Conclusion/Summary: Given the rapid evolution of therapies used to treat FL and DLBCL, these findings fill a crucial data gap in real-world evidence on patient characteristics and treatment patterns in R/R DLCBL and R/R FL in the UK, FRA, and DE. There is an unmet need in DLBCL and FL. As novel treatments for patients with DLBCL and FL are currently in development, it is important to better understand the patients being treated for these conditions and the current treatment landscape. [Display omitted] DisclosuresGalaznik:Takeda Pharmaceuticals International Co.: Employment. Way:Seattle Genetics: Research Funding; Kantar Health: Employment.

Risk factors of Viridans Streptococci bloodstream infection in children with Acute leukemia: Case control study.

Background: Viridans Streptococci (VS) bacteremia in patients with fever and leukemia has significantly increased over the last years. Risk factors described in this population include severe neutropenia, oral mucositis, administration of high-dose cytosine arabinoside, and antimicrobial prophylaxis with either trimethoprim-sulfamethoxazole or a fluoroquinolone. Literature on pediatric patients is scarce Methods & Materials: Case Control retrospective study. Patients with Acute Leukemia admitted between July 2016 and October 2017 in a high-complexity pediatric hospital were included. Patients with fever and VS bacteremia were defined as cases. Patients with fever were defined as controls. Two controls were included by each case. Predisposing factors, clinical and microbiological characteristics were compared. STATA 10 was used Results: n: 90 (30 cases and 60 controls). Fifty one (57%) were male. Mean age was 67 months (IQR 38-107) St mitis/oralis was the most frequent (27/30), followed by St. salivarius (2/30) and St. sanguinis (1/30). Out of 30 isolates of VS 10% exhibited penicillin resistance and 30% intermediate penicillin resistance. Twenty percent of the strains were resistant to ceftriaxone In bivariate analysis, AML (OR 6.8, 95% CI 2.5- 18.2 p < 0.001), severe neutropenia (OR 16.9, 95%CI 2.1-133.1, p 0.007), high doses cytosine arabinoside (OR 4.0 95% IC 1.6- 10.4 p 0.004), oral mucositis (OR 2.9 95%IC 1.0- 8.8 p 0.048) and intensive care unit requirements (OR 11.2 95%IC 2.2-57.2 p 0.005) were associated with VS bacteremia. No association with the use of central venous catheter, co-trimoxazole prophylaxis, previous antibiotics or viral coinfection was found After adjustment by multivariate analysis, variables that remained associated with increased risk of VS bacteremia were AML (OR 6.8 95%IC 1.9-24.2 p 0.003), severe neutropenia (OR 10.1 95%IC 1.2-85.8 p 0.034) and oral mucositis (OR 7.3 95%IC 1.6-33.1 p 0.010) Conclusion: The isolation of VS has become frequent in immunocompromised individuals. AML, severe neutropenia, and the presence of oropharyngeal mucositis were risk factors associated with VS in this study

Effect of high dose cytosine arabinoside on quantitative EEG in patients with acute myeloid leukemia.

Background EEG activity is considered an index of functional state of brain. Chemotherapy (CT), used for non-central nervous system (CNS) cancer, can cross the blood brain barrier and contribute to changes in the functional state of brain that can alter background EEG activity. Quantitative EEG (qEEG) is superior to conventional EEG in the detection of subtle alterations of EEG background activity and for this reason, the use of qEEG might assist the clinician in evaluating the possible effect of CT on the CNS. The nucleoside analog cytosine arabinoside (Ara-C) is one of the milestone chemotherapeutic agents used for treatment of acute myeloid leukemia (AML). Our observational study evaluates the possible effect of Ara-C on the qEEG of patients with AML, without CNS involvement. We conducted an observational study on newly diagnosed AML patients without CNS involvement, undergoing treatment with Ara-C to analyze the possible effect of Ara-C high doses on EEG background activity using qEEG analyses. A total of nine AML patients, 5 with Ara-C i.v. high dose (≥3g/m(2)die), 4 with standard dose (100mg/m(2)die) underwent qEEG (at rest, during hyperpnoea, mental arithmetic task and blocking reaction). We compared the EEG background activity of the two groups at baseline and after 6months. Statistical analysis showed no significant differences between the two groups in mean relative power for all frequency bands, at rest and during hyperpnoea, mental arithmetic task and blocking reaction. Our data indicate that high dose Ara-C i.v. did not induce significant changes on EEG background activity in our patients. Future research in this area could include prospective studies that would combine qEEG and neuropsychological testing to assess the impact of CT on brain functions.

High-Dose Cytosine Arabinoside Chemotherapy of Burkitt Lymphoma: Advocating Sustainable Strategies for Capacity Building in Systemic Cancer Care in Nigeria

Abstract Background: Major factors of treatment failure in Burkitt lymphoma (BL) in Nigerian children include drug resistance and the central nervous system (CNS) “sanctuary effect”. A phase II randomized trial of high-dose cytosine arabinoside was designed to address both problems. Materials and methods: Children with advanced BL, with or without CNS involvement, seen at the University College Hospital, Ibadan, Nigeria from 1984 to1985, and with life expectancy of at least one month, were randomized to an investigational (R-I) treatment regimen of cyclophosphamide (CTX) 1000 mg/m2 IV day 1, Vincristine (VCR) 2·0 mg/m2 IV day 1, cytosine arabinoside (AC) 50 mg/m2 q12hr × 6 doses in cycles 1 and 4, and 1000 mg/m2 q12hr × 4 doses and 50 mg/m2 q12hr × 2 doses for cycles 2 and 3 cycles q14days × 4cycles; or a standard regimen (R II) of CTX 1000 mg/m2 IV day 1, VCR 2·0 mg/m2 IV day 1, AC 50 mg/m2 q12hr × 6 doses q14days × 4 cycles. AC 50 mg/m2 was given intrathecally on days 1 and 5 of each cycle. Results: Complete remission rate (CR) in R-I vs R-II was 9/9 (100%) vs 6/11 (54.5%), partial response 0/9 vs 4/11 (36·4%), non-response 0/9 vs 1/11 (9·1%) and probability of overall survival (OS) 64% vs 19%. Challenges encountered then, including manpower inadequacies and unreliable drug supply continue to impact management of BL three decades later as reported from 10 Nigerian institutions between 1984 and 2014, with cost related, public health support, and manpower deficiencies resulting in poor outcomes (CR<35%, and OS< 5%). Conclusion: HDAC overcomes drug resistance and CNS sanctuary effect in BL and could serve as basis for cancer chemotherapy research in sub-Sahara Africa, provided cultural deficiencies are addressed.

Long Term Remission of a Primary Intracerebral Hodgkin Lymphoma in a Patient Previously Treated With Azathioprine

Background: primary central nervous Hodgkin Lymphoma is a very rare event that occurs in less than 0.2% of cases, most of them in immunosuppressed patients. Case presentation: We describe a 59 year-old man with a 20 year history of ulcerative colitis treated with azathioprine during 6 years who developed a primary central nervous system Hodgkin Lymphoma. Inmunohistochemical study was positive for Epstein-Barr virus showing a type II latency pattern. The patient was treated with chemotherapy regimen consisting on high dose methotrexate and cytosine arabinoside achieving complete remission that remains more than five years after diagnosis. Conclusions: To the best of our knowledge we present the first case in the literature of a primary central nervous system hodgkin lymphoma in a immunossupressed patient due to azathioprine with a long remission after chemotherapy alone.

High-dose cytosine arabinoside-induced symptomatic bradycardia

Cardiac complications of high-dose cytosine arabinoside (HiDAC), although rare, predominantly include pericarditis, pericardial effusion and cardiomyopathy (with concurrent use of cyclophosphamide). Clinically significant arrhythmias associated with HiDAC, although reported in the literature, are rare. The following case report has for the first time used the Naranjo Scale to document a high-probability association (definite adverse drug reaction) of cytarabine with symptomatic sinus bradycardia.

Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial

AbstractThis largest prospective multicenter trial for adult patients with Burkitt lymphoma/leukemia aimed to prove the efficacy and feasibility of short-intensive chemotherapy combined with the anti-CD20 antibody rituximab. From 2002 to 2011, 363 patients 16 to 85 years old were recruited in 98 centers. Treatment consisted of 6 5-day chemotherapy cycles with high-dose methotrexate, high-dose cytosine arabinoside, cyclophosphamide, etoposide, ifosphamide, corticosteroids, and triple intrathecal therapy. Patients >55 years old received a reduced regimen. Rituximab was given before each cycle and twice as maintenance, for a total of 8 doses. The rate of complete remission was 88% (319/363); overall survival (OS) at 5 years, 80%; and progression-free survival, 71%; with significant difference between adolescents, adults, and elderly patients (OS rate of 90%, 84%, and 62%, respectively). Full treatment could be applied in 86% of the patients. The most important prognostic factors were International Prognostic Index (IPI) score (0-2 vs 3-5; P = .0005), age-adjusted IPI score (0-1 vs 2-3; P = .0001), and gender (male vs female; P = .004). The high cure rate in this prospective trial with a substantial number of participating hospitals demonstrates the efficacy and feasibility of chemoimmunotherapy, even in elderly patients. This trial was registered at www.clinicaltrials.gov as #NCT00199082.

Abstract 4142: Capacity building in cancer management in Africa: Envisioning a future from past challenges

Abstract Sub-Saharan African institutions, especially the Uganda Cancer Institute in Kampala, Uganda, led in the development of chemotherapy (CMT) for lymphoma subtypes between 1950 and 1980. Recent WHO emphasis on global non-communicable diseases indicates a need for regional HC paradigm shift in a region long inundated with communicable diseases. Expected barriers in capacity building in medical oncology there are illustrated with challenges of experimental management of Burkitt's lymphoma (BL) at the University College Hospital, Ibadan, Nigeria (UCHIN), where from 1/1984 to 12/1985, a study of tolerability and practicability of high dose cytosine arabinoside (HDAC) CMT was initiated. Included were children (chd) with a diagnosis of BL Ziegler's Stage C or D with or without CNS involvement (CNS±), and life expectancy of at least one month, whose parents/guardians were willing to give oral consent. 60 chd were to be assigned randomly to either the standard treatment (RII) or the investigational (RI) protocol. RI was: Cyclophosphamide (CTX) 1000mg/m2 IV day 1, Vincristine (VCR) 2.0mg/m2 IV day 1, cytosine arabinoside (AC) 50mg/m2 q12hr x 6 doses in cycles 1 and 4, and 1000mg/m2 q12hr x 4 doses and 50mg/m2 q12hr x 2 doses for cycles 2 and 3 cycles q14days x 4cycles. R II was: CTX 1000mg/m2 IV day 1, VCR 2.0mg/m2 IV day 1, AC 50mg/m2 q12hr x 6 doses q14days x 4 cycles. AC 50mg/m2 was given intrathecally days 1 and 5 of each cycle. See Table for results. *MDI: Mean dose intensity. HDAC based CMT was well tolerated with more effective control of systemic and CNS disease compared to conventional CMT. Challenges encountered included ethical issues of medical research in the midst of socio-economic deprivation, technical and manpower inadequacies, unreliable drug supply leading to CMT modifications, communication, lack of compliance and unreliable accessibility to follow-up. Persistence of these problems after &amp;gt;2 decades signals a need for cultural change at all community levels: government, HC administration and among categories of providers. Table of resultsR-IR-IIp-VALUEDEMOGRAPHY#RANDOMIZED14 (30)16 (30)M/F10/410/6AGE9.5±3.58.5±2.5&amp;gt;0.5STAGEC56D-CNS+46D-CNS-43MDI OF AGENTSVCR0.350.520.09CTX382.6466.40.16IV-AC936.0139.50.001IT-AC33.942.00.034OUTCOMES#EVALUATED1012CR9/95/12PR0/95/12NR0/92/12OS (%)59200.21 Citation Format: Christopher K. O. Williams. Capacity building in cancer management in Africa: Envisioning a future from past challenges. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4142. doi:10.1158/1538-7445.AM2014-4142

Dose Intensification of Methotrexate and Cytarabine During Intensified Continuation Chemotherapy for High-risk B-Precursor Acute Lymphoblastic Leukemia

To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL). From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy. Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase. Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.

Acute Megakaryoblastic Leukemia in Children: Diagnosis and Management Challenges in Resource-Poor Countries

Acute Megakaryoblastic Leukemia (AMKL) is a rare subtype of acute myeloid leukemia classified as AML M7 by the French-American-British (FAB) Leukemia Cooperative Study Group. We reviewed the records of children aged less than 18 years with AMKL during the period from January 2003 to December 2010. The diagnosis of AMKL was established on the basis of the FAB criteria and confirmed by immunophenotyping. Eight cases were assigned for this period. The incidence rate of AMKL was 5.5 % of AML. The median age at the time of diagnosis was 1 year. The karyotype presented translocation (1, 22) in two cases. One girl had Down syndrome (DS). Treatment included two inductions based on daunorubicin and cytosine arabinoside (7+3) followed by two consolidations with high dose of cytosine arabinoside (16 g/m 2 ). Complete remission (CR) was achieved in 3 patients (43%). One patient underwent allogeneic stem cell transplant (SCT) and is still enjoying continuous CR 5 years after treatment. Other patients died from failure or relapse. In this small series from a single institution, reported incidence of AMKL is underestimated probably due to the difficulties of diagnosis. The prognosis was poor, particularly because of unavailability of intensified chemotherapy treatment and allogeneic SCT.