High-dose cytarabine-mitoxantrone versus hyper-CVAD in adult acute lymphoblastic leukemia and Burkitt’s lymphoma: A single center experience of two induction regimens.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7076-7076
Author(s):  
Gurpreet Singh Lamba ◽  
Rahul Pawar ◽  
Abhishek Marballi ◽  
Sang-Joon Lee ◽  
Delong Liu

7076 Background: This is a retrospective analysis of 111 newly diagnosed adult ALL patients treated between January 1994 and January 2012 at Westchester Medical Center. Methods: Patients received induction chemotherapy with either high dose mitoxantrone and high-dose Ara-c (HDAM, n=62) or Hyper-CVAD (n=49). The patient characteristics are summarized in the table. OS, CR duration and time to recurrence were estimated using the Kaplan-Meier product estimate methods and comparative study was conducted based on Log-rank test. Differences in CR rates by treatment and by prognostic factors were analyzed using Chi-squared test and Fisher’s exact test. Results: The CR rate was 85% in the HDAM group and 84% in the HyperCVAD group. The median OS was 22.7 months (m), (95% CI 15.3-38.3 m) for the entire cohort, 21.4 m (95% CI 13.3 - 35.5 m) for HDAM arm and 26.8 m (95% CI 11.7 - 63.3 m) for HyperCVAD arm. The OS for patients with Philadelphia chromosome positive or t(4,11) was 13.2 m (95 % CI 9.5 – 26.8 m). In an analysis of the entire cohort for differences in CR rates based on prognostic factors, WBC < 10,000 was the only favorable factor toward CR (p=0.049). Other prognostic factors including cytogenetics, cell type, age, LDH, were not statistically significant. Conclusions: HDAM and Hyper-CVAD appear to be comparable in CR induction and overall survival in this single institution retrospective analysis. These two regimens should be compared in a large multicenter randomized study. [Table: see text]

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4589-4589
Author(s):  
Woondong Jeong ◽  
Delong Liu ◽  
Sreedhar Katragadda ◽  
Qiuhu Shi ◽  
Tauseef Ahmed ◽  
...  

Abstract Seventy-three consecutive adult patients with newly diagnosed ALL and lymphoblastic lymphoma were treated with either high-dose cytarabine /mitoxantrone (Ara-C/Mito) or Hyper-CVAD between January 1994 and January 2005 at the Westchester Medical Center. The regimens were chosen according to investigators’ preferences. The two induction regimens were either Ara-C 3 g/m2/d for 5 days and mitoxantrone 80 mg/m2 on day 2 (52 patients) or Hyper-CVAD regimen (21 patients) containing four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate and Ara-C. All patients who were in CR received consolidation and maintenance therapy after induction. In Ara-C/Mito group, 45 (87%) of 52 patients achieved a complete remission (CR), 2 (4%) had resistant disease and 5 (9%) had died during remission induction in median follow-up of 48 months (range, 0.5 – 109 months). In Hyper-CVAD group, 16 (76%) of 21 patients achieved a CR, 4 (19%) had resistant disease and 1 (5%) had died during remission induction in median follow-up of 12months (range, 0.5 – 43 months). The difference of CR rate between the two groups was not statistically significant. (p=0.31). The overall survival (OS) of AraC/Mito group was 21 months (95% confidence interval [CI], 13 – 38 months), with a 3-year and 5-year OS of 36%, and 30%, respectively. In Hyper-CVAD group, OS was 26 months (95% CI, 26 -NR ), with a 3-year OS of 40%. The difference of OS between the two groups was not statistically significant (p=0.24). In Ara-C/Mito, median CR duration was 34 months (95% CI, 13-) and in Hyper-CVAD, median CR duration was not reached. In a combined multifactorial analysis of the two groups for prognostic factors, Age (<35) was the only favorable factor toward OS (p=0.03). Other prognostic factors including cytogenetics, cell type, WBC, LDH, were not statistically significant. In conclusion: Ara-C/Mito and Hyper-CVAD appear to be comparable in terms of CR rate, toxic death, and OS in this single institution retrospective analysis. It will be interesting to compare the two induction regimens in a large multicenter randomized study. AraC/Mito vs Hyper-CVAD Regimen N Med F/U CR CR duration OS 3yr OS 5yr OS NR: median not reached. M: month AraC /Mito 52 48m 87% 34m 21m 36% 30% Hyper-CVAD 21 21m 76% NR 26m 40% NR p=0.31 p=0.24


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4961-4961
Author(s):  
Pandora Ashley ◽  
Mark Holguin ◽  
Juhee Song

Abstract Abstract 4961 A retrospective study was conducted to ascertain if the use of thalidomide, revlimid and or velcade was associated with improved survival compared to melphalan and prednisone or vincristine, adriamycin and dexamethasone (VAD). To avoid possible confounding issues of treatment with high dose chemotherapy and stem cell rescue, those patients were excluded from this analysis. From 1997 to 2003, 98 patients diagnosed with myeloma and treated at Scott & White Memorial Hospital using non-transplant containing regimens were identified through the Scott & White Tumor Registry. Patients were divided into two groups based on treatment received. One group was treated with melphalan and prednisone or VAD chemotherapy (59 patients) and the second group was treated with regimens that included thalidomide, revlimid, or velcade (39 patients). Median survival times were estimated for the entire cohort and each treatment group. Kaplan-Meier estimates of the survival by treatment received were estimated and log-rank test was performed to compare the survival distributions of the two treatment groups. Five year survivals of the 2 groups were compared using the Z test. Median follow-up time for the entire cohort is 32.6 months (95% CI: 24.4-37.6) Median survivals are 38.7 months (95% CI 32.7-58.5) for the thalidomide/revlimid/velcade group and 24.4 months (95% CI: 14.4-35.7) for the melphalan and prednisone or VAD group. Five year Kaplan-Meier survival estimates are 0.3452 (95% CI: 0.2007-0.4945) for the thalidomide/revlimid/velcade group and 0.1325 (95% CI: 0.0593-0.2354) for the melphalan and prednisone or VAD group. The difference in survival between the two groups is statistically significant with p value of 0.0179. In this retrospective analysis, treatment with newer agents such as thalidomide, revlimid or velcade is associated with a significant improvement in survival compared to melphalan and prednisone or VAD. Disclosures No relevant conflicts of interest to declare.


Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 486
Author(s):  
Richard E. Evenhuis ◽  
Ibtissam Acem ◽  
Anja J. Rueten-Budde ◽  
Diederik S. A. Karis ◽  
Marta Fiocco ◽  
...  

Age is a known prognostic factor for many sarcoma subtypes, however in the literature there are limited data on the different risk profiles of different age groups for osteosarcoma survival. This study aims to provide an overview of survival in patients with high-grade osteosarcoma in different age groups and prognostic variables for survival and local control among the entire cohort. In this single center retrospective cohort study, 402 patients with skeletal high-grade osteosarcoma were diagnosed and treated with curative intent between 1978 and 2017 at the Leiden University Medical Center (LUMC). Prognostic factors for survival were analyzed using a Cox proportional hazard model. In this study poor overall survival (OS) and event-free survival (EFS) were associated with increasing age. Age groups, tumor size, poor histopathological response, distant metastasis (DM) at presentation and local recurrence (LR) were important independent prognostic factors influencing OS and EFS. Differences in outcome among different age groups can be partially explained by patient and treatment characteristics.


2013 ◽  
Vol 31 (6) ◽  
pp. 676-683 ◽  
Author(s):  
Susan O'Brien ◽  
Gary Schiller ◽  
John Lister ◽  
Lloyd Damon ◽  
Stuart Goldberg ◽  
...  

Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi48-vi48
Author(s):  
James Cantrell ◽  
Pawan Acharya ◽  
Sara Vesely ◽  
Michael Confer ◽  
Ozer Algan ◽  
...  

Abstract BACKGROUND Chordomas are rare tumors arising from the embryonal notochord presenting at the base of skull, spine, or sacrum. Pediatric chordomas (PC) comprise less than 5% of all chordomas and are more likely to be atypical or dedifferentiated. Evidence for management is limited to single institution series with 5-year overall survival (OS) between 60-100%. METHODS Using the NCDB Participant User File, a retrospective observational cohort study was performed. The cohort was defined using the bone-soft-tissue, brain, and central nervous system databases selecting for cases with chordoma ICD-03 codes and age ≤ 25 years. Kaplan Meier method, log-rank test, and Cox proportional hazards regression were performed. RESULTS 297 patients from 2004-2017 met inclusion criteria for descriptive analysis with 269 cases included for survival analysis. Mean age was 16.9 years, with 10% less than age 5. The cohort was 55% female, 8% Black, and 79% White. Primary sites included bones of the skull (70%), spine (22%), and pelvis (6%). Regarding treatment, 7% had no resection, 49% sub-total resection (STR), 33% gross-total resection (GTR), and 11% unspecified resection. 51% received radiation therapy with 46% of those receiving proton therapy. 7% received chemotherapy. The 1, 3, 5, and 10-year OS was 95%, 86%, 77%, and 72%. Selected prognostic factors from univariable OS model for OS analysis included: age &gt; 5 (HR 0.30 (95% CI 0.16-0.57) p = 0.0002), surgical resection [GTR (HR 0.28 (95% CI 0.12-0.63) p = 0.0023) and STR (HR 0.27 (95% CI 0.12-0.59) p = 0.0011)], and radiation dose ≥ 7200cGy (HR 0.40 (95% CI 0.16-0.99) p = 0.047). CONCLUSION In the largest cohort reported for PC, 3 and 10-year OS was 86% and 72%. Age, surgery, and radiation dose are important prognostic factors. Propensity score analysis to gauge effect of treatment, tumor, and patient characteristics on OS is forthcoming.


1999 ◽  
Vol 17 (2) ◽  
pp. 445-445 ◽  
Author(s):  
Gregory H. Reaman ◽  
Richard Sposto ◽  
Martha G. Sensel ◽  
Beverly J. Lange ◽  
James H. Feusner ◽  
...  

PURPOSE: Infants represent a very poor risk group for acute lymphoblastic leukemia (ALL). We report treatment outcome for such patients treated with intensive therapy on consecutive Children's Cancer Group (CCG) protocols. PATIENTS AND METHODS: Between 1984 and 1993, infants with newly diagnosed ALL were enrolled onto CCG-107 (n = 99) and CCG-1883 (n = 135) protocols. Postconsolidation therapy was more intensive on CCG-1883. On both studies, prophylactic treatment of the CNS included both high-dose systemic chemotherapy and intrathecal therapy, in contrast to whole-brain radiotherapy, which was used in earlier studies. RESULTS: Most patients (> 95%) achieved remission with induction therapy. The most frequent event was a marrow relapse (46 patients on CCG-107 and 66 patients on CCG-1883). Four-year event-free survival was 33% (SE = 4.7%) on CCG-107 and 39% (SE = 4.2%) on CCG-1883. Both studies represent an improvement compared with a 22% (SE = 5.1%) event-free survival for historical controls. Four-year cumulative probabilities of any marrow relapse or an isolated CNS relapse were, respectively, 49% (SE = 5%) and 9% (SE = 3%) on CCG-107 and 50% (SE = 5%) and 3% (SE = 2%) on CCG-1883, compared with 63% (SE = 6%) and 5% (SE = 3%) for the historical controls. Independent adverse prognostic factors were age less than 3 months, WBC count of more than 50,000/μL, CD10 negativity, slow response to induction therapy, and presence of the translocation t(4;11). CONCLUSION: Outcome for infants on CCG-107 and CCG-1883 improved, compared with historical controls. Marrow relapse remains the primary mode of failure. Isolated CNS relapse rates are low, indicating that intrathecal chemotherapy combined with very-high-dose systemic therapy provides adequate protection of the CNS. The overall unsatisfactory outcome observed for the infant ALL population warrants the future use of novel alternative therapies.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1858-1858 ◽  
Author(s):  
Daniel J. DeAngelo ◽  
Lewis B. Silverman ◽  
Stephen Couban ◽  
Suzanne Dahlberg ◽  
Philip C. Amrein ◽  
...  

Abstract Background: In children with ALL, current chemotherapy regimens produce an event-free survival (EFS) of greater than 80%. Adults with ALL have a much poorer prognosis, with EFS rates of 30–40%. Recent retrospective studies suggest that young adult patients may have superior outcomes when treated on more intensive pediatric regimens, but prospective studies are lacking. A phase II trial was performed in an effort to determine if an intensive pediatric regimen can be administered to adults with ALL. Methods: The therapeutic backbone of this protocol is based upon the high-risk arm of the DFCI Childhood ALL Consortium Protocol 00–01. Patients with newly diagnosed ALL were enrolled and received intensive multiagent remission induction chemotherapy, which included doxorubicin, prednisone, vincristine, high-dose methotrexate, high-dose asparaginase, and triple intrathecal therapy. CNS prophylaxis included triple intrathecal therapy and cranial radiation. Intensification therapy consisted of 3 week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine and 30 weeks of high-dose asparaginase that was individually dosed in order to maintain asparagine depletion. Continuation therapy consisted of 3 week courses of vincristine, dexamethasone, methotrexate and 6-mercaptopurine for a total of 2 years from an established complete remission (CR). Results: 71 patients have been enrolled to date. Although there was no initial upper age restriction, the protocol was amended to include only patients between the ages of 18–50 with de novo ALL; this amendment excluded 4 patients from the analysis. Two patients were enrolled but never received therapy. Demographic data are available for 61 evaluable patients. The median age was 28 years, (range, 18–50), 65% were male, 75% had B-lineage phenotype, and 13% were Philadelphia chromosome positive. In the 54 patients for whom response data was available, the 4 week CR rate was 82%. Among the patients who had the opportunity to complete Intensification therapy, asparaginase data was available for 23 patients, 18 (78%) of whom completed all 30 weeks. One death occurred during induction therapy from sepsis. Four patients developed grade 3 pancreatitis and one patient died of grade 5 pancreatitis. The latter case represented the only remission death on study. There were two cases of osteonecrosis, 10 cases of thrombosis/embolism and 12 cases of neutropenic infection that occurred during the post-remission period. At the median follow-up time of 18.4 months, the estimated EFS is 75% (95%CI: 61–89%) and the overall survival is 79% (95%CI: 65–93%). Conclusions: These results suggest that administration of a dose intensified pediatric-like strategy is feasible. Although the high EFS rate requires longer follow up and larger confirmatory studies, such intensive treatment of young adults with ALL could represent a major therapeutic advance.


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