scholarly journals Healthcare Costs Associated with Adult Philadelphia Chromosome-Negative (Ph-) Acute Lymphoblastic Leukemia (ALL) in the US

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5940-5940 ◽  
Author(s):  
Nicole Princic ◽  
Xue Song ◽  
Vincent Lin ◽  
Ze Cong
Keyword(s):  
Economic Burden ◽  
Healthcare Costs ◽  
Index Date ◽  
Lymphoblastic Leukemia ◽  
Small Sample ◽  
Discharge Diagnosis ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
The Us

Abstract Background: Ph- ALL in adults is a very rare disease with poor prognosis. Literature on the economic burden of Ph- ALL in adults is sparse. This study quantifies the economic burden by estimating the total healthcare costs of Ph- ALL in adults from initial diagnosis until relapse and from relapse until death from US payer's perspective. Methods: This is a retrospective, observational study using the MarketScan® Commercial Claims and Encounters (Commercial) database, which contains information on approximately 40 million employees and their dependents. Patients were included if they are newly diagnosed with ALL, defined by absence of ALL ICD-9-CM diagnosis (204.0x) 90 days prior the first ALL diagnosis, and have at least one inpatient claim with ALL diagnosis (204.0x) as the primary discharge diagnosis during the study period (4/1/2009-12/31/2014). Patients with less than 6 months of continuous enrollment prior to the index date were excluded. Patient with Ph+ disease (defined by the use of any prescriptions for tyrosine kinase inhibitors) were also excluded. Relapse ALL cases were defined by patients with records of relapse code (204.02). The admission date of the hospitalization with ALL primary discharge diagnosis was the index date. Patients were followed from the index date until death, loss of follow up, or end of the study period, whichever came first. Direct medical and pharmacy costs (plan reimbursed amounts) were the primary outcomes in this analysis. All costs were inflated to 2014 dollars based on the Medical Care component of the Consumer Price Index. Costs were evaluated monthly and cumulatively. To account for censoring in cost data, the Kaplan Meier Survival Estimator (KMSE) method (Lin et al Biometrics 1997;53:419-434) was employed to adjust the monthly costs by the Kaplan Meier curves. The total per patient cost from ALL diagnosis to death was calculated by adding the 12-month KMSE adjusted cumulative costs from ALL diagnosis to relapse and from relapse to death. Results: A total of 362 newly diagnosed patients with Ph- ALL met all the study criteria. The average age was 41.2 (SD 15.1). Mean duration of follow-up was 409.5 days (SD 371.6) and 19% (n=69) of patients relapsed during follow-up. Mean monthly costs were the greatest during the first month following initial ALL diagnosis ($150,969) and during the first month following the relapse diagnosis ($155,321). The KMSE adjusted cumulative costs from initial ALL diagnosis until relapse per patient were estimated to be $412,231 at 6 months, and $595,509 at 12 months. The KMSE adjusted cumulative costs per patient from relapse to death were estimated to be $414,787 at 6 months, and $501,084 at 12 months. When combined, the calculated total cost per patient from newly diagnosed to relapse and from relapse until death was $1,096,593. Conclusions and Limitations: Ph- ALL in adults is associated with significant economic burden in the US. For an average patient, the total healthcare cost from ALL diagnosis until death is more than $1 million with almost half of the expense incurred after relapse. The primary limitation for this analysis is the small sample size for the relapse ALL patients. However, it is expected given the rarity of the disease. Disclosures Princic: Truven Health Analytics: Employment. Song:Truven Health Analytics: Employment; Amgen: Other: This study was funded by Amgen.. Lin:Amgen: Employment. Cong:Amgen: Employment.

The lines of loco-regional therapies received and the healthcare economic burden of patients newly diagnosed with hepatocellular carcinoma in the United States.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 286-286
Author(s):  
Brian Seal ◽  
Abdulla M. Abdulhalim ◽  
Melissa Lingohr-Smith ◽  
Jay Lin
Keyword(s):  
Radiation Therapy ◽  
Economic Burden ◽  
Healthcare Costs ◽  
Index Date ◽  
The United States ◽  
Newly Diagnosed ◽  
Ablative Therapy ◽  
Regional Therapy ◽  
The Us

286 Background: Hepatocelluar carcinoma (HCC) is one of the fastest growing causes of cancer-related deaths in the US. The objectives of this study were to examine the lines of loco-regional therapies received and the healthcare economic burden of patients newly diagnosed with HCC in the US. Methods: Patients (≥18 years of age) diagnosed with HCC who received ≥1 loco-regional therapy (index date) after diagnosis were identified from the MarketScan Commercial and Medicare Supplemental databases (July 1, 2013-May 31, 2018). Patients were required to have ≥6 months of continuous insurance enrollment before the index date and ≥1 month after (follow-up period). The follow-up period was censored when patients received any systemic therapy. During the follow-up periods, the number of patients who received radiation therapy, ablative therapy, and embolization procedures (transarterial embolization/chemoembolization [TAE] and radioembolization [TARE]) were examined. All-cause and HCC-related healthcare costs (total and patient out-of-pocket [OOP] payments per patient per month [PPPM]) were also measured. Results: Among the 2,101 patients newly diagnosed with HCC who received ≥1 loco-regional therapy, median age was 64 years and 75.0% were male; the mean follow-up duration was 11.5 months. During the follow-up periods, 28.1% (n = 590) received radiation therapy, 27.3% (n = 574) ablative therapy, and 77.3% (n = 1,623) embolization therapy (TAE: 68.7% [n = 1,443]; TARE: 20.7% [n = 434]); 30.9% of patients received multiple loco-regional therapies. During the follow-up periods, total all-cause healthcare costs were a mean of $20,316 (OOP: $378) PPPM, of which 70.7% ($14,359; OOP: $227 PPPM) were HCC-related. The breakdown of healthcare costs is shown in the table. Conclusions: According to the findings of this large-scale real-world analysis of patients newly diagnosed with HCC in the US, a vast majority received at least one embolization procedure. The monthly healthcare economic burden of patients with HCC treated with local-regional therapies is relatively high. [Table: see text]

scholarly journals Real World Treatment Outcomes and Cost Among Newly-Diagnosed Multiple Myeloma Patients Treated with Bortezomib and Dexamethasone in Combination with Cyclophosphamide or Lenalidomide

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5924-5924
Author(s):  
Lin Xie ◽  
Kejal Parikh ◽  
Safiya Abouzaid ◽  
Shivani Pandya ◽  
Onur Baser ◽  
...  
Keyword(s):  
Healthcare Costs ◽  
Research Funding ◽  
Index Date ◽  
Cox Regression ◽  
Treatment Patterns ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Equity Ownership ◽  
Baseline Characteristics

Abstract Background: Despite an increasing incidence of multiple myeloma (MM) with advancing age and life expectancy, there are few real-world claims-based analyses describing treatment patterns and healthcare costs associated with use of novel treatments.1,2 This study aimed to assess treatment patterns and healthcare costs among newly-diagnosed MM patients using the US Medicare database. Methods: This retrospective study identified adult patients with ≥2 claims for MM (International Classification of Diseases, 9th Revision, Clinical Modification code: 203.0x) 30 days apart and ≥1 treatment during the identification period (01JAN2011-30JUN2014) from the 100% Medicare dataset. Medicare dataset contains medical and pharmacy claims submitted by healthcare providers, facilities and pharmacy. It includes comprehensive demographic information for beneficiaries and a longitudinal picture of their healthcare utilizations and costs .The initial course of therapy (COT1) date was the index date and included all treatments prescribed within 60 days of this date. Patients were required to have continuous enrollment for 12 months pre- and ≥6 months post-index date unless the patient died in <6 months (follow-up period), ≥1 full cycle of therapy with a valid COT1 regimen, no evidence of prior MM diagnosis or treatment (including autologous stem cell transplant [ASCT]), and no evidence of ASCT in the follow-up period. COT2 was defined as the earliest occurrence of: addition of a new drug or switch in regimen after the first 60 days, restart of a previous regimen after >180-day gap, or dose increase from maintenance to relapse therapy. Steroids (dexamethasone/prednisone [d]) were assumed to be included regardless of whether or not they were observed during the study period; this did not impact the ongoing COT. Treatment patterns and healthcare costs during the follow-up period were compared among those initiating lenalidomide (R) with bortezomib (V) ± steroids (RVd) and cyclophosphamide (Cy) with bortezomib (bor) ± steroids (CyBorD). Time-to-next treatment (TTNT) was defined as the duration from initiation of COT1 plus any treatment gaps until the initiation of COT2. Kaplan Meier (KM), Cox regression analyses and a generalized linear model (GLM) were performed to evaluate TTNT, assess the impact of various predictors on TTNT, and estimate the 12-month per patient per month (PPPM) total healthcare costs respectively among patients initiating RVd and CyBorD. Results:After accounting for the patient selection criteria, 9.9% (n=345) of patients initiated RVd and 5.0% (n=175) initiated CyBorD as COT1. CyBorD-treated patients were significantly older (76.1 vs. 74.2 years, p=0.0009) with a higher age-adjusted Charlson Comorbidity Index score (9.5 vs 8.8, p=0.0119). The overall mean duration of COT1 was significantly longer among patients treated with RVd vs CyBorD (13.2 vs 8.5 months, p<0.0001). Among patients who completed COT1, the mean duration of COT1 was longer for patients treated with RVd vs. CyBorD (12.8 vs 6.7 months, p<0.0001). A higher percentage of patients treated with CyBorD progressed to COT2 (27.4%, vs 21.7% p=0.1491) versus RVd, however no significant difference was observed. Among patients who progressed to COT2, TTNT was significantly shorter among those treated with CyBorD vs RVd (Mean: 7.9 vs 15.9 months, p<0.0001). KM analysis suggested that patients initiating CyBorD progressed much faster than patients receiving RVd. After adjusting for baseline characteristics using Cox regression, TTNT remained significantly shorter for CyBorD vs. RVd treated patients (hazard ratio: 2.2, 95% confidence interval: 1.5-3.4, p=0.0002). Results from GLM analysis suggested that adjusted total PPPM cost during 12 months follow up was higher among patients treated with RVd vs. CyBorD ($13,941 vs $9,340, p=0.0001), and the majority of the extra cost are due to higher pharmacy costs for patients treated with RVd. Conclusion: Patients on RVd incurred higher costs, however, they progressed significantly slower and their TTNT was almost twice as long as for CyBorD patients. The difference remained significant after controlling for baseline characteristics including markers for higher disease severity among patients on CyBorD. 1Song X, et al. Curr Med Res Opin 2015;32(1):95-103 2Teitelbaum A, et al. Oncologist 2013;18:37-45 Disclosures Xie: Celgene: Research Funding. Parikh:Celgene Corporation: Employment, Equity Ownership, Research Funding. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Pandya:Celgene: Research Funding. Baser:Janssen Pharmaceuticals: Research Funding. Patel:Celgene: Consultancy.

scholarly journals Comparison of Real-world Outcomes Between Patients Treated with Tapentadol ER or Oxycodone CR

10.36469/9905 ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 221-232
Author(s):  
Mike Durkin ◽  
Jacqueline Pesa ◽  
Jessica Lopatto ◽  
Rachel Halpern ◽  
Damon Van Voorhis ◽  
...  
Keyword(s):  
Emergency Department ◽  
Emergency Department Visit ◽  
Healthcare Costs ◽  
Index Date ◽  
Opioid Therapy ◽  
Care Utilization ◽  
Research Database ◽  
Before And After ◽  
Pain Patients

Background: The objective of this study was to compare health care utilization and costs between matched cohorts of chronic pain patients treated with the opioids tapentadol extended release (ER) or oxycodone controlled release (CR). Methods: This retrospective study used claims data from the Optum Research Database. Commercial and Medicare Advantage adult patients with ≥1 prescription fill for oxycodone CR or tapentadol ER between September 1, 2011 and September 30, 2012 were eligible. The date of the first observed oxycodone CR or tapentadol ER claim was the index date. Patients had continuous health plan enrollment for 6 months before and after the index date, ≥ 90 days supply of opioid therapy, and no index drug claims in the preindex period. Patients were propensity score matched in a 1:2 ratio (tapentadol ER : oxycodone CR). Results: The attributes of the matched cohorts (1,120 tapentadol ER and 2,240 oxycodone CR patients) appeared similar. In the 6 month post-index period, lower proportions of the tapentadol ER cohort than the oxycodone CR cohort had ≥1 inpatient stay (14.6% versus 20.5%; p&lt;0.001) and ≥1 emergency department visit (33.4% versus 37.5%; p=0.021). The tapentadol ER compared with the oxycodone CR cohort had higher mean pharmacy costs ($4,263 versus $3,694; p &lt;0.001), lower mean inpatient costs ($3,625 versus $6,309; p&lt;0.001), and lower mean total healthcare costs ($16,510 versus $19,330; p=0.004). Conclusions: During follow-up, total mean healthcare costs were lower among tapentadol ER patients than oxycodone CR patients, and tapentadol ER patients were less likely to have an inpatient admission or emergency department visit.

scholarly journals Fractionated Inotuzumab Ozogamicin Combined with Low-Intensity Chemotherapy Provides Very Good Outcome in Older Patients with Newly Diagnosed CD22+ Philadelphia Chromosome-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: First Results from the EWALL-INO Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 511-511
Author(s):  
Patrice Chevallier ◽  
Thibault Leguay ◽  
Michael Doubek ◽  
Francoise Huguet ◽  
Cyril Salek ◽  
...  
Keyword(s):  
B Cell ◽  
Older Patients ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Newly Diagnosed ◽  
Cell Precursor ◽  
Inotuzumab Ozogamicin ◽  
Low Intensity

Abstract On behalf of the GRAALL group, the Czech Republic ALL group, the Finland ALL group and the EWALL group. Introduction. Treatment of older patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains an unmet medical need. Inotuzumab ozogamicin (INO), an anti-CD22 antibody conjugated to calicheamicin, is approved for the treatment of relapsed/refractory BCP-ALL in adults, sinusoidal obstruction syndrome (SOS) being the major adverse event associated with INO. A previous first line study conducted by the MDACC in pts 60 years or older successfully used INO in combination with a lower intensity version of the hyper-CVAD (mini-hyper-CVD). Due to the occurrence of SOS, the total doses were fixed at 1.3 mg/m² for cycle 1 followed by 3 cycles at 1 mg/m² (Kantarjian H et al. Lancet Oncol, 2018). Here, we aimed to assess the activity and safety of fractionated INO at a reduced dosage in combination with low-intensity chemotherapy as frontline therapy for older pts with CD22+ Philadelphia chromosome-negative (Ph-neg) BCP-ALL. Methods. EWALL-INO is a single arm prospective phase 2 multicentric study conducted in European centers belonging to the EWALL group. Eligibility criteria were pts aged 55y or older, performance status ≤2, and newly diagnosed CD22+ (20% or more of positive blast cells) Ph-neg BCP-ALL without central nervous system involvement. After a prephase including 5 days (D) of dexamethasone (DEX) 10mg per D and a single intrathecal injection (IT), the induction regimen was begun and split in 2 parts. Induction part I (Induc1) consisted of one triple IT, vincristine (VCR) 2 mg (1 mg over 70y) D1 D8 D15 D22 and DEX 20 mg D1D2 D8D9 D15D16 D22D23 combined with 3 injections of INO (0.8 mg/m² D1, 0.5 mg/m² D8 and D15). Induction part II (Induc2) was offered to pts in CR or CRp (CR with platelets &lt; 100 G/l) after Induc1 or as salvage therapy. Induc2 consisted of DEX 20mg D1D8, cyclophosphamide (CY) 300 mg/m² D1 to D3, one triple IT D2 and 2 injections of INO (0.5 mg/m² D1 and D8). Pts in CR/CRp were programmed to receive 6 blocks of consolidation (Ara-C 1.5g/m²/12h adapted to renal clearance D1D2 and DEX 10mg/12h D1D2, cycles 1 and 4; Methotrexate (MTX) 1.5 g/m² over 24h D1, VCR 1 or 2 mg D1, one triple IT D2 and 6-mercaptopurin (6-MP) D1 to D7, cycles 2 and 5; CY 500 mg/m² D1D2, VP16 75 mg/m² D1D2, one triple IT D2 and MTX 25 mg/m² D1, cycles 3 and 6) followed by a POMP maintenance (VCR, 6-MP, MTX, DEX) during 18 months. Allograft was allowed after at least 3 blocks of consolidation at the discretion of the investigators. The evaluable population was pts who received at least 1 dose of INO. Analyses were by modified intention to treat and performed JUN 28, 2021. All pts gave informed consent. The study is registered at ClinicalTrials.gov under the NCT number: NCT03249870. Results. Between DEC 29, 2017 and JUN 22, 2021, 115 pts (out of 130 planned pts) were enrolled including 6 pts with screen failure. The first 90 eligible pts (up to MAR 1, 2021) were considered for this analysis to obtain a minimum of 4 months follow-up. Median age was 69y (range 55-84) and median follow-up for alive pts was 1.18 years (range 0.3-3.5). At time of analysis, 90 and 88 pts had started induc1 and induc2, respectively. Treatment related mortality was 2.2% (2/90) and CR/CRp rate was 85.5% (77/90, 6 CRp) after induc1. Three cases relapsed between induc1 and induc2 and 5 pts were salvaged by induc2 allowing to a CR/CRp rate of 87.7% (79/90, 8 CRp) after induc2. One pts died from refractory disease during induc2. One, 2, 3 4 and 5 injections of INO were administered to 2 (2.2%), 2(2.2%), 11 (12.2%), 2 (2.2%) and 73 pts (81.1%) respectively. Only 6 pts were allografted. One-year OS was estimated to be 78.5% (95%CI 68-85.9) and median OS was not reached. One-year relapse free survival was 74.5% (95CI 63.5-82.6) (Figure 1). Grade 3-4 liver toxicity was observed in 8 pts (8.8%) during the study including 3 pts (3.3%) developing SOS, 2 related to INO during induc1 and one occurred after transplant. Twenty-nine pts died during the follow-up, 16 from relapses (overall incidence 18%) and 13 from adverse events (overall incidence 14.4%), including one COVID19 fatal infection during consolidation. Conclusion. Fractionated inotuzumab ozogamicin at reduced doses (0.8/0.5/0.5/0.5 mg/m²) combined with low-intensity chemotherapy is a very active and well tolerated frontline therapy for older patients with CD22+ Ph-neg BCP-ALL. Figure 1 Figure 1. Disclosures Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Huguet: Novartis: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Celgene: Other: Advisor; BMS: Other: Advisor; Amgen: Other: Advisor; Pfizer: Other: Advisor. Raffoux: ABBVIE: Consultancy; PFIZER: Consultancy; CELGENE/BMS: Consultancy; ASTELLAS: Consultancy. Boissel: CELGENE: Honoraria; Servier: Consultancy, Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; PFIZER: Consultancy, Honoraria; JAZZ Pharma: Honoraria, Research Funding; SANOFI: Honoraria. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. Rousselot: Incyte, Pfizer: Consultancy, Research Funding. OffLabel Disclosure: Inotuzumab ozogamicin as first line therapy in newly diagnosed CD22+ Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia

Improved Postoperative Survival for Intraductal- Growth Subtype of Intrahepatic Cholangiocarcinoma

2016 ◽  
Vol 82 (11) ◽  
pp. 1133-1139 ◽  
Author(s):  
Laura L. Dover ◽  
Rojymon Jacob ◽  
Thomas N. Wang ◽  
Joseph H. Richardson ◽  
David T. Redden ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Small Sample Size ◽  
Tumor Stage ◽  
Small Sample ◽  
Postoperative Survival ◽  
Rank Test ◽  
Intraductal Growth ◽  
Kaplan Meier ◽  
Disease Free

Intrahepatic cholangiocarcinoma (ICC) is classified according to the following subtypes: mass-forming (MF), periductal infiltrating (PI), and intraductal growth (IG). The aim of this study is to measure the association between ICC subtypes and patient survival after surgical resection. Data were abstracted on all patients treated with definitive resections of ICC at a single institution between 2000 and 2011 with at least three years follow-up. Survival estimates were quantified using Kaplan-Meier curves and compared using the log-rank test. There were 37 patients with ICC treated with definitive partial hepatectomies with a median survival of 33.5 months. Tumor stage (P < 0.0001), satellitosis (P < 0.001), lymphovascular space invasion (P = 0.003), and macroscopic subtype (P = 0.003) were predictive of postoperative survival. Disease-free survivals for MF, PI, and IG subtypes, respectively, were 30 per cent, 0 per cent, and 57 per cent (P = 0.017). Overall survivals among ICC macroscopic subtypes were as follows: MF 37 per cent, PI 0 per cent, and IG 71 per cent (P = 0.003). Although limited by the small sample size of this rare cancer, this study demonstrates significant differences among macroscopic subtypes of ICC in both disease-free survivals and overall survivals after definitive partial hepatectomy.

Outcome of Dana-Farber Cancer Institute (DFCI) Consortium Protocol 95–01 for Children with Newly Diagnosed Acute Lymphoblastic Leukemia (ALL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 679-679 ◽  
Author(s):  
Lewis B. Silverman ◽  
Donna E. Levy ◽  
Virginia K. Dalton ◽  
Steven E. Lipshultz ◽  
Richard D. Gelber ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Intrathecal Chemotherapy ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Patients Âgés ◽  
Cranial Radiation ◽  
Erwinia Asparaginase ◽  
To Receive

Abstract DFCI Consortium Protocol 95–01 was designed to minimize therapy-related morbidity for children with newly diagnosed ALL without compromising efficacy. Patients were considered high risk (HR) if they met any of the following criteria: 1) white blood cell count (WBC) ≥ 50,000/microliter, 2) age between < 1.00 years or ≥ 10.00 years, 3) presence of leukemia blasts at diagnosis in a cytocentrifuged cerebrospinal fluid specimen, 4) presence of a mediastinal mass, 5) T-cell immunophenotype, or 6) presence of the Philadelphia chromosome. All other patients were considered standard risk (SR). The protocol included three randomizations designed to evaluate whether acute and late toxicities could be reduced, including comparisons of 1) Erwinia and E.coli asparaginase given weekly for 20 weeks during post-remission consolidation (SR and HR patients), 2) intrathecal chemotherapy given with or without 18 Gy cranial radiation as central nervous system (CNS)-directed treatment (SR patients only), and 3) doxorubicin given with or without dexrazoxane, a potential cardioprotectant agent, during remission induction and post-remission consolidation (HR patients only). Between 1996 and 2000, 491 eligible patients (ages 0-18 years) were enrolled, 272 of whom were classified as SR and 219 HR. With 4.6 years median follow-up, the estimated 5-year event-free survival (EFS) was 81 ± 2% for all patients. The 5-year EFS according to risk group was 86 ± 2% for SR and 76 ± 3% for HR patients (p<0.01). Erwinia asparaginase was associated with a decreased incidence of asparaginase-related toxicities compared with E.coli asparaginase (10 % versus 24%, p<0.01), but also significantly more relapses (19% versus 8%, p<0.01), including relapses involving the CNS (6% versus 1%, p<0.01). The 5-year EFS for the 139 patients randomized to Erwinia asparaginase was 78 ± 4% compared with 89 ± 3% for the 148 patients randomized to E.coli asparaginase (p<0.01). The 5-year EFS for SR patients randomized to CNS treatment without radiation (IT-only) was 82 ± 5% compared with 87 ± 4% for those randomized to receive cranial radiation (p=0.35). There were four relapses involving the CNS in the 83 SR patients randomized to IT-only (4.8%) and none in the 80 irradiated patients (0%) (p=0.12). However, three of the four CNS relapses in IT-only SR patients occurred in those who had also been randomized to Erwinia asparaginase. CNS relapses (isolated or combined with other sites) occurred in 1.9% of randomized IT-only SR patients who received E.coli asparaginase. Dexrazoxane did not significantly impact the EFS of HR patients, with a 5-year EFS of 75 ± 5% for the 105 patients randomized to doxorubicin with dexrazoxane compared with 77 ± 4% for the 101 patients randomized to receive doxorubicin alone (p=0.85). We conclude that 1) Erwinia asparaginase is less toxic but also less efficacious than E.coli asparaginase when dosed once weekly during post-remission consolidation, 2) Intensive intrathecal chemotherapy without cranial radiation provides adequate CNS prophylaxis in SR patients in the setting of effective systemic chemotherapy, and 3) Dexrazoxane does not appear to interfere with the anti-leukemic effect of Doxorubicin.

Imatinib Mesylate and Hyper-CVAD (IM-HCVAD) for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4103-4103
Author(s):  
Martha Arellano ◽  
Disni Muringampurath-John ◽  
Pareen J. Shenoy ◽  
Elliott F. Winton ◽  
Beverly Bryan ◽  
...  
Keyword(s):  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Allogeneic Transplantation ◽  
Newly Diagnosed ◽  
Small Cohort ◽  
Cytogenetic Remission ◽  
Lost To Follow Up ◽  
Disease Free

Abstract Abstract 4103 Introduction The addition of IM to hyper-CVAD led to higher rates and longer duration of complete remissions in Ph+ ALL. The purpose of this study is to report single institution experience with IM-HCVAD followed by maintenance IM or allogeneic transplantation in newly diagnosed adult Ph+ ALL treated between 10/02 and 08/08. Methods IRB-approved retrospective analysis of the institutional hematological database. Results Thirty-three patients, median age 51 (22-72), with 8 (24%) older than 60, presented with a median WBC of 24,000/mm3 (range, 2-200) and LDH of 2.6 ULN (1.3-11). Four (12%) had extra-medullary/CSF leukemia. Patients received a median of 7 (range, 1-8) cycles of IM-HCVAD followed by maintenance IM +/- POMP as tolerated (Blood 2004;103:4396-4407). After 2 cycles, 1 patient had primary refractory disease and expired, and 32 (97%) achieved complete hematological and cytogenetic remission. Twenty-four of 32 (75%) subsequently achieved complete molecular remission (CMR). Among those who achieved CMR, 6/24 relapsed with preceding loss of CMR in 4. Four of 8 who did not achieve CMR relapsed. One patient in CR was lost to follow-up after induction. Thirteen (39%) were allografted in CR1 using TBI-based myeloablative (9) or non-myeloablative (4) conditioning and 18 received maintenance IM-based therapy. With a median follow-up of 18.3 months (range, 4.4-76), 10 patients (32%) relapsed (1 post-transplant and 9 during IM maintenance) and received salvage therapy leading to CR2 in 4, of which 1 was successfully allografted, and 3 remain in CR2 with a follow-up of 20, 36, and 60 months. Eleven patients died (6 from GVHD/infection, and 5 from relapsed refractory leukemia). For the 13 allograft recipients in CR1 disease-free (DFS) and overall survival (OS) were 15, and 18 months; and 15 months and 20 months for the 18 IM maintenance patients, respectively (Figure). WBC > 30,000/mm3 and residual disease detected by flow cytometry after 2 cycles were associated with decreased OS (p < 0.03). A trend for lower survival was noted among African American patients (p= 0.07). Conclusion The addition of IM to hyper-CVAD is associated with high rates of CR (97%) in newly diagnosed Ph+ ALL. In this relatively small cohort with a short follow-up, peripheral blood PCR did not predict outcomes. Ph+ALL patients are candidates for novel maintenance regimens. Disclosures: Off Label Use: Imatinib combined with the hyper-CVAD chemotherapy. Khoury:Novartis Oncology: Honoraria.

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