DOCSLIB.ORG

Busulfan–Melphalan Followed by Autologous Stem Cell

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Busulfan–Melphalan Followed by Autologous Stem Cell Bone Marrow Transplantation (2016) 51, 1265–1267 © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0268-3369/16 www.nature.com/bmt LETTER TO THE EDITOR Busulfan–Melphalan followed by autologous stem cell transplantation in patients with high-risk neuroblastoma or Ewing sarcoma: an exposed–unexposed study evaluating the clinical impact of the order of drug administration Bone Marrow Transplantation (2016) 51, 1265–1267; doi:10.1038/ survival (OS) was the time from study entry (that is, the first day bmt.2016.109; published online 25 April 2016 of HDC) to death or the last follow-up, whichever occurred first. EFS was the time from study entry to disease progression, a second malignancy, death or the last follow-up, whichever High-dose chemotherapy (HDC) and autologous stem cell occurred first. OS and EFS were estimated using the Kaplan–Meier transplantation (ASCT) have improved the prognosis of high-risk method. Patients from the two treatment groups (Bu–Mel neuroblastoma and metastatic Ewing sarcoma.1,2 The impact of and Mel–Bu) of the same age at diagnosis were matched. the drugs in the HDC regimen was first demonstrated in a The association of the treatment group with toxicity and study performed in the Gustave Roussy Pediatrics Department. efficacy outcomes was assessed using Cox regression models It showed improved survival for patients with stage 4 stratified on matched pairs and adjusted for other confounding neuroblastoma who received a combination of busulfan (Bu) factors, such as the year of diagnosis, VOD prophylaxis and age at and melphalan (Mel).3 These results were confirmed in a diagnosis. European randomized study (HR-NBL1/SIOPEN), and this From 2002 to 2012, 81 patients were included in this study: 46 combination is now administered worldwide to patients with patients treated with Mel–Bu (median year of diagnosis: 2008) and high-risk neuroblastoma.4,5 This HDC was used as a consolidation 35 patients with Bu–Mel (median year of diagnosis: 2004), regimen in metastatic Ewing sarcoma and proved beneficial for followed by ASCT. The characteristics of the two populations event-free survival (EFS).6 are described in Table 1. The median age at diagnosis was However, the toxicity of Bu–Mel is severe with specific 4 years in both groups (range: 0–20). Patients were diagnosed endothelial toxicity and a high rate of hepatic veno-occlusive with either a high-risk neuroblastoma (65), mainly metastatic disease (VOD), non-infectious interstitial pneumonitis or disease at diagnosis (54) or a localized tumor with N-MYC pulmonary hypertension. Reducing the incidence of these amplification (9), or a Ewing sarcoma (16), mainly metastatic complications remains a major issue for the future strategy for disease at diagnosis (13). Most of the tumors were located in the administering this regimen. Preclinical and clinical studies adrenal glands (47) or limbs (8), and were stage 4 (70:66 at suggest that the order of administering alkylating agents can diagnosis and 4 at relapse between the diagnosis and ASCT). influence the toxicity of HDC. When Bu is given first in Metastatic tumors had mainly spread to the bone (47) and combination with another alkylating agent, it can increase the bone marrow (45). No significant difference was observed in toxicity of the second drug by inducing glutathione depletion the conventional chemotherapy received before HDC (type and and/or lower the metabolism of the second chemotherapeutic number of courses, number of drugs) between the two agent.7,8 groups. Prophylactic therapy against VOD was administered to Based on these pharmacological data, patients o20 years old 57 patients: either oral ursodeoxycholic acid (26 patients: at diagnosis of a high-risk neuroblastoma or Ewing sarcoma, not 9 Mel–Bu and 17 Bu–Mel treated between 2002 and 2008) included in ongoing protocols, have been treated with the Mel–Bu or IV defibrotide (31 patients: 18 Mel–Bu and 13 Bu–Mel treated combination with Mel administered before Bu since 2002 in the between 2006 and 2012). Gustave Roussy Pediatrics Department. The primary aim of the VOD occurred in 16 Mel–Bu and 10 Bu–Mel patients, mostly present study was to perform an exposed (Mel–Bu order, that is, grade II disease (11 and 6 patients, respectively). The new order) - unexposed (Bu–Mel order, that is, classic order) study 4-week incidence of grade II/III VOD was 31% (95% in order to evaluate and compare toxicity VOD in two groups of confidence interval (CI): 19–45%) and 17% (95% CI: 8–33%) for patients. We also evaluated and compared the efficacy (EFS), a Mel–Bu and Bu–Mel patients, respectively (Figure 1a). Before secondary aim, to determine the potential benefit of changing the 3 months after ASCT, one patient in the Mel–Bu group order of administration of the two alkylating agents in future experienced non-infectious interstitial pneumonitis and one protocols. patient in the Bu–Mel group developed infrasystemic pulmonary Bu–Mel patients received either oral (before 2003) or IV hypertension with a favorable outcome. One patient in the (after 2003) Bu for 4 days followed by one dose of IV Mel 24 h Mel–Bu group died of acute respiratory distress syndrome after after the last dose of Bu, whereas Mel–Bu patients received Mel surgical resection of the tumor, 34 days after ASCT. In the followed by Bu. ASCT was performed 24–48 h after the last dose multivariate analysis, no significant difference in the risk of of chemotherapy. Supportive care was comparable to IV grade II/III VOD was observed between the two groups granulocyte colony stimulating factor (5 μg/kg per day) (hazards ratio = 2.1 (95% CI: 0.8–5.9), P-value = 0.14). No significant administered from day 5 after ASCT to the end of neutropenia. difference was found between the two groups in other toxicities The definition of VOD fulfilled the Seattle criteria and its severity such as digestive or hematological toxicity or even infectious was graded according to the Bearman toxicity score. Overall complications (data not shown). Two toxic deaths occurred only in Letter to the Editor 1266 respectively. Regarding the two efficacy outcomes, 3-year EFS Table 1. Patient characteristics (Figure 1b) and 3-year OS (Figure 1c) were, respectively, 61% – – – Characteristics Melphalan-Busulfan Busulfan-Melphalan (95% CI: 44 76%) and 69% (95% CI: 52 83%) for the Mel Bu combination (Mel-Bu) combination (Bu-Mel) patients, and 55% (95% CI: 37–72%) and 65% (95% CI: 46–81%) for the Bu–Mel patients. In the multivariate analysis, no significant Overall 46 35 difference in the two efficacy outcomes was observed between Sex the two groups: EFS (hazards ratio = 1.1 (95% CI: 0.4–3.1), Male 30 (65%) 17 (49%) P-value = 0.9) and OS (hazards ratio = 1.2 (95% CI: 0.3–4.0), Age at diagnosis (years) P-value = 0.8). In addition, no difference in EFS was observed Median, range 4 (0–19) 4 (0–20) between neuroblastoma and Ewing sarcoma (hazards ratio = 1.5 (95% CI: 0.5–5.2), P-value = 0.5). Years of diagnosis The morbidity of the Bu–Mel combination, mainly related to the Median, range 2008 (2003–2011) 2004 (2002–2011) high incidence of diffuse endothelial injury and especially hepatic VOD, remains a major concern.9 Diagnosis The impact on toxicity of the order of administering alkylating Neuroblastoma 37 (80%) 28 (80%) agents was demonstrated with the Bu–Cy regimen commonly Ewing sarcoma 9 (20%) 7 (20%) administered before allogeneic transplantation. Cyclophospha- – Primary tumor site mide pharmacokinetics were compared in the Bu Cy and Cy-TBI Adrenal 28 (60%) 19 (55%) combinations. Higher exposure to cyclophosphamide and its toxic Limbs 4 (9%) 4 (11%) metabolite, 4-hydroxy cyclophosphamide (4OHCY) was demon- Thorax 4 (9%) 1 (3%) strated in the Bu–Cy combination than in its Cy-TBI counterpart. Abdomen 0 5 (14%) – a The incidence of VOD with the Bu Cy regimen could be explained Other 10 (22%) 6 (17%) by enhanced exposure to 4OHCY.7 An interval of o24 h between Bu and cyclophosphamide administration caused lower cyclopho- Stage of tumorb II 2 (5%) 0 sphamide clearance and a higher incidence of VOD. The III 3 (6%) 2 (6%) administration of Bu induces glutathione depletion and inhibition IV 38 (83%) 32 (91%) of hepatic cytochrome activity leading to an increase in Not precised 3 (6%) 1 (3%) 4OHCY.10,11 Preclinical studies compared the myeloablative and c Extension of tumor immunosuppressive effects of Bu–Cy and Cy–Bu in mice. Bone 27 (71%) 20 (63%) Hepatic toxicity was significantly lower in the Cy–Bu group with Bone marrow 26 (68%) 19 (59%) faster bone marrow engraftment.12 The lower liver toxicity of Ganglionic 7 (18%) 10 (31%) Cy–Bu was confirmed, with no impact on long-term engraftment Pulmonary 1 (3%) 5 (16%) 13 Othera 42in the same mouse model. In two clinical studies comparing patients receiving Bu–Cy or Cy–Bu before allogeneic or Initial chemotherapy autologous transplantation for hematological malignancies, Rapid COJEC 17 (37%) 17 (49%) hepatic toxicity was lower in the Cy–Bu group with no impact on engraftment, survival or relapse.8,14 A pharmacodynamic study Follow-up (months) of Bu was conducted in pediatric patients with a solid Median, 95% CI 40.6 (23.0–47.1) 52.6 (24.2–60.6) tumor receiving Bu-containing HDC. The incidence of VOD in – Duration of hospitalization (days) the Bu Mel group was not correlated with systemic exposure to Median, range 27 (21–57) 28 (12–50) Bu unlike that observed in the Bu-Thiotepa group. This finding supported the impact of Mel on the incidence of VOD observed.
Load more

Recommended publications
  • Arsenic Trioxide As a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study
    Arsenic Trioxide as a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study Shakeel Modak1, Pat Zanzonico2, Jorge A. Carrasquillo3, Brian H. Kushner1, Kim Kramer1, Nai-Kong V. Cheung1, Steven M. Larson3, and Neeta Pandit-Taskar3 1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; 2Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York; and 3Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York sponse rates when compared with historical data with 131I-MIBG Arsenic trioxide has in vitro and in vivo radiosensitizing properties. alone. We hypothesized that arsenic trioxide would enhance the efficacy of Key Words: radiosensitization; neuroblastoma; malignant the targeted radiotherapeutic agent 131I-metaiodobenzylguanidine pheochromocytoma/paraganglioma; MIBG therapy 131 ( I-MIBG) and tested the combination in a phase II clinical trial. J Nucl Med 2016; 57:231–237 Methods: Patients with recurrent or refractory stage 4 neuroblas- DOI: 10.2967/jnumed.115.161752 toma or metastatic paraganglioma/pheochromocytoma (MP) were treated using an institutional review board–approved protocol (Clinicaltrials.gov identifier NCT00107289). The planned treatment was 131I-MIBG (444 or 666 MBq/kg) intravenously on day 1 plus arsenic trioxide (0.15 or 0.25 mg/m2) intravenously on days 6–10 and 13–17. Toxicity was evaluated using National Cancer Institute Common Metaiodobenzylguanidine (MIBG) is a guanethidine analog Toxicity Criteria, version 3.0. Response was assessed by Interna- that is taken up via the noradrenaline transporter by neuroendo- tional Neuroblastoma Response Criteria or (for MP) by changes in crine malignancies arising from sympathetic neuronal precursors 123I-MIBG or PET scans.
    [Show full text]
  • An Evaluation of Engraftment, Toxicity and Busulfan Concentration in Children Receiving Bone Marrow Transplantation for Leukemia Or Genetic Disease
    Bone Marrow Transplantation (2000) 25, 925–930 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease AM Bolinger1, AB Zangwill1, JT Slattery2,3, D Glidden4, K DeSantes5, L Heyn6, LJ Risler3, B Bostrom7 and MJ Cowan8 1University of California at San Francisco, Department of Clinical Pharmacy; 2Department of Pharmaceutics, University of Washington; 3Fred Hutchinson Cancer Research Center; 4University of California at San Francisco, Department of Epidemiology and Biostatistics; 5University of Wisconsin, Department of Pediatrics; 6University of California at San Francisco, Department of Nursing; 7University of Minnesota, Department of Pediatrics; and 8University of California at San Francisco, Department of Pediatrics, San Francisco, CA, USA Summary: children exhibit average busulfan steady-state concen- trations (Css) or an area under the curve (AUC) substan- Autologous recovery is a major problem with busulfan tially less than do older children or adults.7–9 The Css corre- as a marrow ablative agent in conditioning children for sponds to the AUC over a dosing interval divided by the allogeneic BMT. Data suggest the average concentration 6 h between doses. The AUC over a dosing interval is equal of busulfan at steady state (Bu Css) is critical for suc- to the AUC from the time the first dose is ingested to infin- cessful engraftment. We prospectively evaluated busul- ity if no subsequent doses are taken. A Css of 900 ng/ml fan pharmacokinetics in 31 children (age 0.6–18 years) is equal to an AUC of 1350 ␮m × min.
    [Show full text]
  • Mitomycin C in the Treatment of Chronic Myelogenous Leukemia
    Nagoya ]. med. Sci. 29: 317-344, 1967. MITOMYCIN C IN THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA AKIRA HosHINo 1st Department of Internal Medicine Nagoya University School oj Medicine (Director: Prof. Susumu Hibino) SUMMARY Studies made of the treatment with 66 courses of mitomycin C in 28 patients with chronic myelogenous leukemia are reported. The effect of mitomycin C was investigated according to the relation between drug and host factors, comparison with the effects of other agents, and drug resistance. Patients with less hematological and clinical symptoms responded better to mitomycin C therapy. The remission rate of cases treated intravenously with mitomycin C was 93.8% and of cases treated orally with mitomycin C was 72.0%. The remission rate of the total cases (intravenous and oral) treated with mitomycin C was 77.3%. The therapeutic effect of mitomycin C is considered to be equal or be somewhat superior to the effect of busulfan as a result of data on the occurrence of resistance, cross resistance, development of acute blastic crisis and life span. Busulfan was effective in patients resistant to mitomycin C, and mitomycin C did not clinically show cross resistance to alkylating agents. Two patients resist· ant to mitomycin C recovered the sensitivity to mitomycin C after treatment with busulfan or 6-mercaptopurine. Side effects were observed in 39.4% of 66 cases, but severe side effect causing suspension of mitomycin C was rare. I. INTRODUCTION Human leukemia serves as a useful investigative model in which the de­ finite effect of anti-cancer agents can be evaluated quantitatively by factors such as the improvement of hematological findings and clinical symptoms, the remission rate, and the prologation of life span.
    [Show full text]
  • Standard Oncology Criteria C16154-A
    Prior Authorization Criteria Standard Oncology Criteria Policy Number: C16154-A CRITERIA EFFECTIVE DATES: ORIGINAL EFFECTIVE DATE LAST REVIEWED DATE NEXT REVIEW DATE DUE BEFORE 03/2016 12/2/2020 1/26/2022 HCPCS CODING TYPE OF CRITERIA LAST P&T APPROVAL/VERSION N/A RxPA Q1 2021 20210127C16154-A PRODUCTS AFFECTED: See dosage forms DRUG CLASS: Antineoplastic ROUTE OF ADMINISTRATION: Variable per drug PLACE OF SERVICE: Retail Pharmacy, Specialty Pharmacy, Buy and Bill- please refer to specialty pharmacy list by drug AVAILABLE DOSAGE FORMS: Abraxane (paclitaxel protein-bound) Cabometyx (cabozantinib) Erwinaze (asparaginase) Actimmune (interferon gamma-1b) Calquence (acalbrutinib) Erwinia (chrysantemi) Adriamycin (doxorubicin) Campath (alemtuzumab) Ethyol (amifostine) Adrucil (fluorouracil) Camptosar (irinotecan) Etopophos (etoposide phosphate) Afinitor (everolimus) Caprelsa (vandetanib) Evomela (melphalan) Alecensa (alectinib) Casodex (bicalutamide) Fareston (toremifene) Alimta (pemetrexed disodium) Cerubidine (danorubicin) Farydak (panbinostat) Aliqopa (copanlisib) Clolar (clofarabine) Faslodex (fulvestrant) Alkeran (melphalan) Cometriq (cabozantinib) Femara (letrozole) Alunbrig (brigatinib) Copiktra (duvelisib) Firmagon (degarelix) Arimidex (anastrozole) Cosmegen (dactinomycin) Floxuridine Aromasin (exemestane) Cotellic (cobimetinib) Fludara (fludarbine) Arranon (nelarabine) Cyramza (ramucirumab) Folotyn (pralatrexate) Arzerra (ofatumumab) Cytosar-U (cytarabine) Fusilev (levoleucovorin) Asparlas (calaspargase pegol-mknl Cytoxan (cyclophosphamide)
    [Show full text]
  • Cardio-Oncology: Basics and Knowing When You Need an Echo
    1/10/2018 Cardio-oncology: Basics and Knowing When You Need an Echo Vera H. Rigolin, MD, FASE, FACC, FAHA Professor of Medicine Northwestern University Feinberg School of Medicine Medical Director, Echocardiography Laboratory Northwestern Memorial Hospital Chicago, Illinois President, American Society of Echocardiography No Disclosures • Acknowledgement: Nausheen Akhter, MD, Director of the cardio-oncology program at Northwestern 1 1/10/2018 Introduction • The number of cancer therapies have significantly increased • Cancer survival has improved • A number of cancer therapies have cardiotoxic effects Cardiotoxic Syndromes Associated with Chemo Agents associated with LV Agents associated with dysfunction hypertension • Bevacizumab (Avastin) • Anthracylines • Cisplatin • Mitoxanthrone • IL-2 • Cyclophosphamide • Trastuzumab Agents associated with Other toxic effects • Ifosfamide • Tamponade or endomyocardial • All-trans retinoic acid fibrosis (Busulfan) • Hemorrhagic Myocarditis Agents associated with (Cyclophosphamide) ischemia • Bradycardia (Taxol, Thalidomide) • 5-FU • Raynaud’s (Vinblastine) • Cisplatin • Autonomic neurop (Vincristine) • Capecitabine (Xeloda) • Long QT (Arsenic trioxide) • Pulm fibrosis (Bleo) • IL-2 Yeh et al. Circulation 2004 2 1/10/2018 Angiogenesis Inhibitors • Angiogenesis is a key factor for tumor growth and survival. • Angiogenesis inhibitors have shown to improve outcomes in various malignancies • Tumor growth suppression achieved by: – Direct inhibition of VEGF ligand’s ability to target receptor (bevacizumab, ramucirumab, aflibercept) – Small molecules that inhibit tyrosine kinases (sunitinib, sorafenib, pazopanid, vandetanib, vatalanib, cobazantinib, axitinib, regorafenib) Mechanisms of Action of Angiogenic Inhibitors Maurea N et. J Cardiovasc Med 2016;17(suppl):e-19-e26 3 1/10/2018 Odds ratio for adverse cardiac events due to angiogenesis inhibitors Abdel-Qadir H et al. Cancer Treatment Reviews 20178;53:120-127. J Am Soc Echocardiogr2014;27:911-39.
    [Show full text]
  • Conditioning Regimens Intravenous Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in Infants: Clinical and Pharmacokinetic Results
    Bone Marrow Transplantation (2003) 32, 647–651 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt Conditioning Regimens Intravenous busulfan for allogeneic hematopoietic stem cell transplantation in infants: clinical and pharmacokinetic results JH Dalle1, D Wall2, Y Theoret1, M Duval1, L Shaw3, D. Larocque1, C Taylor2, J Gardiner3, MF Vachon1 and MA Champagne1 1Service d’He´matologie et Oncologie Pe´diatrique, Hoˆpital Sainte Justine, Montre´al QC, Canada; 2Methodist Children’s Hospital of South Texas, San Antonio, TX,USA; and 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA Summary: tion, very wide inter- and intrapatient systemic exposure is observed with two- to sixfold of coefficient variability. High-dose busulfan is an important component of This wide bioavailability range may be linked to erratic myeloablative regimens. Variable drug exposure may intestinal absorption (7 emesis), variable hepatic metabo- occur following oral administration. Therefore, the use lism, circadianrhythm, geneticpolymorphism of a-glu- of intravenous busulfan has been advocated. Previous tathione-S-transferase, initial diagnosis, previous work has suggested a cumulative dosage of 16 mg/kg for treatment, drug–drug interaction and/or patient age. haematopoietic transplantation in children less than 3 Hepatic and renal clearance mechanisms are generally years of age, but only limited data are available in infants. underdeveloped and inefficient in the neonate, but they Pharmacokinetics of intravanous busulfan administered at may change dramatically in the months following birth. the suggested dosage were studied in 14 infants (median Thus, pharmacokinetically guided dosage adjustment age 4.7 months). Busulfan plasma concentrations were appears mandatory, particularly in children.5,7–12 measured by either GC-MS or HPLC-UV.
    [Show full text]
  • Induction of Sister Chromatid Exchanges and Chromosomal Aberrations by Busulfan in Philadelphia Chromosome-Positive Chronic Myeloid Leukemia and Normal Bone Marrow1
    (CANCER RESEARCH 48, 3435-3439, June 15, 1988) Induction of Sister Chromatid Exchanges and Chromosomal Aberrations by Busulfan in Philadelphia Chromosome-positive Chronic Myeloid Leukemia and Normal Bone Marrow1 Reinhard Becher2 and Gabriele Prescher Innere Universitäts-und Poliklinik (Tumorforschung), Westdeutsches Tumorzentrum, Hufelandstrasse 55. 4300 Essen l. Federal Republic of Germany ABSTRACT (5) human tumor cell lines and described a correlation between the sensitivity to chemotherapy measured by the colony-form Cytogenetic effects of busulfan in vitro were studied in normal bone ing efficiency assay and the rate of induced SCE. Furthermore, marrow (nine cases) and Philadelphia chromosome (Ph)-positive cells the clonal heterogeneity of chemotherapy resistance within a (10 cases) of patients with chronic myeloid leukemia. The frequency of single solid tumor was evidenced by different levels of induced chromosome aberrations and sister chromatid exchange (SCE) increased dose dependently. While there were no significant differences between SCE (6). normal and leukemic cells with regard to the induction of chromosome Our intention was to analyze SCE induction by therapeuti- aberrations, the frequency of SCE was significantly lower in Ph-positive cally relevant agents in leukemias. Ph-positive CML was chosen cells than in normal bone marrow. This difference was not only apparent for the study presented here because the leukemic cells can on the basis of the SCE frequency per cell, but also when the SCE easily be distinguished from normal cells by means of the Ph frequency was correlated to the relative chromosome length as shown by chromosome. Secondly, SCE and chromosome breaks in nor the SCE rate per chromosome group.
    [Show full text]
  • Thiotepa, Busulfan, and Cyclophosphamide Or Busulfan
    Annals of Hematology (2019) 98:1657–1664 https://doi.org/10.1007/s00277-019-03667-1 ORIGINAL ARTICLE Thiotepa, busulfan, and cyclophosphamide or busulfan, cyclophosphamide, and etoposide high-dose chemotherapy followed by autologous stem cell transplantation for consolidation of primary central nervous system lymphoma Jaewon Hyung1 & Jung Yong Hong1 & Dok Hyun Yoon1 & Shin Kim1 & Jung Sun Park1 & Chan-sik Park2 & Sang-wook Lee3 & Jeong Hoon Kim4 & Jin Sook Ryu5 & Jooryung Huh2 & Cheolwon Suh1 Received: 10 October 2018 /Accepted: 7 March 2019 /Published online: 15 April 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a suitable consolidation strategy for patients who respond to induction chemotherapy. The purpose of this study was to compare the outcome and toxicity profile of the combination of busulfan, cyclophosphamide, and etoposide (BuCyE) with that of the combination of thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimens of upfront ASCT for consolidation therapy in PCNSL. The PCNSL registry data set, prospectively collected from March 1993 to May 2017 at Asan Medical Center, was reviewed retrospectively. Patients with objective response to induction chemotherapy who received BuCyE or TBC as conditioning regimen for ASCTwere included in the analysis. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Among 241 patients with a diagnosis of PCNSL, 53 received ASCT as upfront consolidation therapy with TBC (28 patients) or BuCyE (25 patients) as conditioning regimen.
    [Show full text]
  • Cancer Drug Costs for a Month of Treatment at Initial Food
    Cancer drug costs for a month of treatment at initial Food and Drug Administration approval Year of FDA Monthly Cost Monthly cost (2013 Generic name Brand name(s) approval (actual $'s) $'s) Vinblastine Velban 1965 $78 $575 Thioguanine, 6-TG Thioguanine Tabloid 1966 $17 $122 Hydroxyurea Hydrea 1967 $14 $97 Cytarabine Cytosar-U, Tarabine PFS 1969 $13 $82 Procarbazine Matulane 1969 $2 $13 Testolactone Teslac 1969 $179 $1,136 Mitotane Lysodren 1970 $134 $801 Plicamycin Mithracin 1970 $50 $299 Mitomycin C Mutamycin 1974 $5 $22 Dacarbazine DTIC-Dome 1975 $29 $125 Lomustine CeeNU 1976 $10 $41 Carmustine BiCNU, BCNU 1977 $33 $127 Tamoxifen citrate Nolvadex 1977 $44 $167 Cisplatin Platinol 1978 $125 $445 Estramustine Emcyt 1981 $420 $1,074 Streptozocin Zanosar 1982 $61 $147 Etoposide, VP-16 Vepesid 1983 $181 $422 Interferon alfa 2a Roferon A 1986 $742 $1,573 Daunorubicin, Daunomycin Cerubidine 1987 $533 $1,090 Doxorubicin Adriamycin 1987 $521 $1,066 Mitoxantrone Novantrone 1987 $477 $976 Ifosfamide IFEX 1988 $1,667 $3,274 Flutamide Eulexin 1989 $213 $399 Altretamine Hexalen 1990 $341 $606 Idarubicin Idamycin 1990 $227 $404 Levamisole Ergamisol 1990 $105 $187 Carboplatin Paraplatin 1991 $860 $1,467 Fludarabine phosphate Fludara 1991 $662 $1,129 Pamidronate Aredia 1991 $507 $865 Pentostatin Nipent 1991 $1,767 $3,015 Aldesleukin Proleukin 1992 $13,503 $22,364 Melphalan Alkeran 1992 $35 $58 Cladribine Leustatin, 2-CdA 1993 $764 $1,229 Asparaginase Elspar 1994 $694 $1,088 Paclitaxel Taxol 1994 $2,614 $4,099 Pegaspargase Oncaspar 1994 $3,006 $4,713
    [Show full text]
  • CNS Relapse in Acute Promyeloctyic Leukemia
    VOLUME 28 ⅐ NUMBER 24 ⅐ AUGUST 20 2010 JOURNAL OF CLINICAL ONCOLOGY DIAGNOSIS IN ONCOLOGY eral blood stem-cell transplantation (SCT) for consolidation, with CNS Relapse in Acute Promyeloctyic high-dose busulfan and cyclophosphamide conditioning.6,7 Five Leukemia months after SCT, the patient presented with 1 week of right-sided headache worse with neck flexion, 3 days of intermittent visual loss in A 42-year-old female was diagnosed with acute promyelocytic her right eye, and paresthesias of the right leg. Magnetic resonance leukemia (APL) with a translocation of chromosomes 15 and 17 image revealed diffuse leptomeningeal enhancement. Figure 1 shows involving the PML and RARA genes. On presentation she met criteria an axial T1-weighted, gadolinium-enhanced image demonstrating ϫ 9 for low-risk disease on the basis of platelet count (50 10 /L) and regions of leptomeningeal enhancement (arrows). Cerebrospinal ϫ 9 1 WBC count (0.8 10 /L). The patient achieved a complete molecu- fluid (CSF) analysis revealed blast cells that were CD33 and CD13 lar remission after induction chemotherapy with all-trans-retinoic positive and HLA-DR negative, and RT-PCR confirmed the presence acid (ATRA) and idarubicin (AIDA) and underwent consolidation of PML-RARA transcripts. Figure 2 shows a diffuse infiltrate of myelo- chemotherapy per the risk-adapted Spanish Cooperative Group for blasts and promyelocytes within the CSF (Fig 2A). On high-power Hematological Malignancies Treatment (PETHEMA) regimen, on view (Fig 2B), several abnormal promyelocytes are noted, with intense 2 completion of which she remained in molecular remission. She azurophilic granules, bilobed nuclei, and dispersed chromatin.
    [Show full text]
  • 2012 NIOSH List of Antineoplastic and Other Hazardous Drugs
    NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012 DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012 DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health This document is in the public domain and may be freely copied or reprinted. Disclaimer Mention of any company or product does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH). In addition, citations to Web sites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not responsible for the content of these Web sites. Ordering Information To receive documents or other information about occupational safety and health topics, contact NIOSH at Telephone: 1–800–CDC–INFO (1–800–232–4636) TTY:1–888–232–6348 E-mail: [email protected] or visit the NIOSH Web site at www.cdc.gov/niosh For a monthly update on news at NIOSH, subscribe to NIOSH eNews by visiting www.cdc.gov/niosh/eNews. DHHS (NIOSH) Publication Number 2012−150 (Supersedes 2010–167) June 2012 Preamble: The National Institute for Occupational Safety and Health (NIOSH) Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings was published in September 2004 (http://www.cdc.gov/niosh/docs/2004-165/). In Appendix A of the Alert, NIOSH identified a sample list of major hazardous drugs.
    [Show full text]
  • MYLERAN® (Busulfan) 2-Mg Scored Tablets
    PRESCRIBING INFORMATION MYLERAN® (busulfan) 2-mg Scored Tablets WARNING MYLERAN is a potent drug. It should not be used unless a diagnosis of chronic myelogenous leukemia has been adequately established and the responsible physician is knowledgeable in assessing response to chemotherapy. MYLERAN can induce severe bone marrow hypoplasia. Reduce or discontinue the dosage immediately at the first sign of any unusual depression of bone marrow function as reflected by an abnormal decrease in any of the formed elements of the blood. A bone marrow examination should be performed if the bone marrow status is uncertain. SEE WARNINGS FOR INFORMATION REGARDING BUSULFAN-INDUCED LEUKEMOGENESIS IN HUMANS. DESCRIPTION MYLERAN (busulfan) is a bifunctional alkylating agent. Busulfan is known chemically as 1,4-butanediol dimethanesulfonate and has the following structural formula: CH3SO2O(CH2)4OSO2CH3 Busulfan is not a structural analog of the nitrogen mustards. MYLERAN is available in tablet form for oral administration. Each scored tablet contains 2 mg busulfan and the inactive ingredients magnesium stearate and sodium chloride. The activity of busulfan in chronic myelogenous leukemia was first reported by D.A.G. Galton in 1953. CLINICAL PHARMACOLOGY Studies with 35S-busulfan: Following the intravenous administration of a single therapeutic dose of 35S-busulfan, there was rapid disappearance of radioactivity from the blood; 90% to 95% of the 35S-label disappeared within 3 to 5 minutes after injection. Thereafter, a constant, low level of radioactivity (1% to 3% of the injected dose) was maintained during the subsequent 48-hour period of observation. Following the oral administration of 35S-busulfan, there was a lag period of ½ to 2 hours prior to the detection of radioactivity in the blood.
    [Show full text]