Epidermal growth factor receptor expression correlates with histologic grade but not microsatellite instability in primary colon carcinomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20023-20023
Author(s):  
R. L. Rego ◽  
A. J. French ◽  
N. R. Foster ◽  
D. J. Sargent ◽  
S. R. Alberts ◽  
...  
Keyword(s):  
Overall Survival ◽  
Microsatellite Instability ◽  
Disease Free Survival ◽  
Receptor Expression ◽  
High Dose ◽  
Colon Cancers ◽  
Egfr Expression ◽  
Primary Colon ◽  
Weighted Score ◽  
Clinicopathological Variables

20023 Background: EGFR is a transmembrane receptor tyrosine kinase belonging to the ErbB family of proteins. Anti-EGFR antibodies have shown efficacy as monotherapy and can enhance cytotoxic chemotherapy in patients with advanced colorectal cancers. We studied EGFR expression in primary colon cancers and its association with, microsatellite instability (MSI), clinicopathological variables and patient survival rates. Methods: Archival colon carcinomas were studied from patients with high risk Dukes’ stage B2 (n = 78) and C (n = 230) patients enrolled in a prior adjuvant trial of 5-fluorouracil, leucovorin plus standard dose or high-dose levamisole (NCCTG 91–46–53). EGFR expression (anti-EGFR H11 antibody, DAKO) was analyzed by immunohistochemistry (IHC) and intensity (0–3+), extent and their product (weighted score) were determined. MSI was analyzed using BAT26 and expression of hMLH1, hMSH2 and hMSH6 proteins by IHC. Patients were censored at 5 years after randomization for DFS and censored at 8 years post study randomization for overall survival (OS) data. Results: EGFR protein expression was detected in 216 of 308 (70%) of Dukes’ B2 and C primary colon carcinomas from patients and localized to the plasma membrane. EGFR expression variables (intensity, extent, weighted score) were increased in poor/undifferentiated compared to moderate/well differentiated tumors (p ≤ 0.036). Similar EGFR expression levels were found in MSI-H (n = 27) versus MSS (n = 203) colon cancers and for other clinicopathological variables. EGFR intensity was more likely moderate (2+) or strong (3+) in Dukes’ C versus B2 tumors (p = 0.088). In addition, higher EGFR intensity (2+, 3+) showed a trend toward worse disease-free survival (5 yr DFS %: 62.2 vs. 71.7; p = 0.095), but not overall survival (p = 0.14). Conclusions: EGFR overexpression is associated with increased tumor aggressiveness as indicated by poor tumor cell differentiation and reduced DFS in colon cancer patients receiving adjuvant 5-FU and levamisole. These findings indicate that EGFR may be an important therapeutic target in the adjuvant setting. [Table: see text]

Microsatellite instability but not thymidylate synthase is a prognostic variable in primary colon cancers from patients treated in 5-FU-based adjuvant studies

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10019-10019
Author(s):  
F. A. Sinicrope ◽  
R. L. Rego ◽  
K. C. Halling ◽  
N. R. Foster ◽  
D. J. Sargent ◽  
...  
Keyword(s):  
Overall Survival ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Thymidylate Synthase ◽  
Dna Mismatch Repair ◽  
Histologic Grade ◽  
Dna Mismatch ◽  
Colon Cancers ◽  
Lower Stage ◽  
Primary Colon

10019 Background: Colon cancers with microsatellite instability (MSI) display resistance to 5-fluorouracil (5-FU), and in vitro resistance can be reversed by restoring DNA mismatch repair proficiency. 5-FU inhibits the thymidylate synthase (TS) enzyme and TS may predict clinical outcome after 5-FU-based chemotherapy. To define molecular predictors of prognosis, we analyzed TS, p53, chromosome 17p allelic imbalance (AI), and patient survival stratified by MSI status. Methods: Primary colon carcinomas from patients enrolled in five 5-FU-based adjuvant therapy trials were analyzed for MSI and 17p AI using 11 microsatellite markers (MSI-H: ≥ 30% of the loci demonstrating instability). For 17p AI, markers included D17S261 and TP53 at or near the p53 locus. Expression of DNA mismatch repair (hMLH1, PharMingen; hMSH2; Oncogene), TS (TS106, Zymed), and p53 (D07, Novacastra) proteins were analyzed by immunohistochemistry. Correlations between markers and associations with overall survival (OS) were determined. Patients were censored at 5 years for DFS and at 8 years post study randomization for overall survival (OS) data. Results: Of 320 Dukes’ stage B2 and C cancers studied, 60 of 320 (19%) were MSI-H. TS expression variables (intensity, extent, weighted score) were similar in MSI-H and MSI stable/low frequency (MSS/MSI-L) cancers; similar results were found using DNA mismatch repair (dMMR) proteins. MSI-H tumors had lower stage (p= 0.0007), fewer metastatic lymph nodes (p= 0.004), and improved OS (vs. MSS/MSI-L tumors; p= 0.01). Loss of dMMR proteins was also associated with better OS (p= 0.006). None of the TS variables were prognostic for OS. Histologic grade (p= 0.0008) and nodal status (p= 0.0002) were associated with OS in contrast to 17p LOH or p53. Only MSI status or dMMR, histologic grade, and tumor stage were independent markers for OS. Conclusions: MSI-H tumors show earlier stage at presentation and better stage-adjusted survival rates. MSI status and TS expression were unrelated and TS was not prognostic, suggesting that TS levels cannot explain therapeutic resistance to 5-FU reported in MSI-H colon cancers. [Table: see text]

scholarly journals Evaluation of The Effectiveness and Side Effects of Radiotherapy in Patients With Primary Nervous System Lymphoma. A Single Center Experience

2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Side Effects ◽  
Disease Free Survival ◽  
Central Nervous System Lymphoma ◽  
Field Size ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.

Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.

1988 ◽  
Vol 6 (9) ◽  
pp. 1491-1500 ◽  
Author(s):  
A E Chang ◽  
T Kinsella ◽  
E Glatstein ◽  
A R Baker ◽  
W F Sindelar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Dose Regimen ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Regimen ◽  
Disease Free

We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.

Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

2006 ◽  
Vol 16 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
B. M. Buttin ◽  
M. A. Powell ◽  
P. J. Goodfellow ◽  
S. N. Lewin ◽  
R. K. Gibb ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Microsatellite Instability ◽  
Medical Records ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Molecular Stratification ◽  
Colon Cancers ◽  
Increased Risk ◽  
Primary Colon ◽  
Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

Second Autologous or Allogeneic Transplantation after the Failure of First Autograft in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3329-3329
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima Saliba ◽  
Marcos de Lima ◽  
Daniel Couriel ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Albumin Level ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Common Causes

Abstract Background: Most patients undergoing high-dose therapy and autologous transplant for multiple myeloma eventually relapse. The optimal salvage treatment for these patients is not very well defined. Both autologous and allogeneic hematopoietic stem cell transplantations have been used for salvage. We analyzed the outcomes of second autologous or allogeneic transplants, performed as salvage in patients relapsing after an autograft. Methods: Fourteen patients received a second autograft for salvage, while thirty-four patients underwent allogeneic transplantation (related 24, unrelated 10). The median age at transplant was 52 years in the autologous group, and 51 years in the allogeneic group. The median interval between the first and the second transplant was 25 months in the autologous group and 17 months in the allogeneic group. The disease characteristics were similar in both autologous and allogeneic groups. Results: With a median follow-up of 10 months among survivors in each group, both autologous and allogeneic transplant groups had a response rate (complete + partial) of 64%. One hundred day nonrelapse mortality was 7% in the autologous group and 12% in the allogeneic group. Median disease-free survival (DFS) was 11 months in the autologous and 6 months in the allogeneic group. Median overall survival (OS) was 29 moths in the autologous and 14 months in the allogeneic group. 1-year DFS was 40% in the autologous group and 22% in the allogeneic group (p = 0.2). 1-year overall survival was 70% in the autologous and 53% in the allogeneic group (p = 0.3). The most common causes of non-relapse mortality were graft vs. host disease (62%) in the allogeneic group, and infections (100%) in the autologous group. On univariate analysis for DFS in allogeneic group, an interval of >1 year between the first and the salvage transplant was the only factor associated with a significantly better outcome (p = 0.01). Disease status at transplant, type of donor, tumor mass, β2 microglobulin level, and serum albumin level did not show any impact on the outcome. Conclusions: Both autografting and allografting are feasible as salvage for myeloma patients relapsing after the first autograft. A slightly better outcome with salvage autografting may be due to decreased toxicity.

Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91

2002 ◽  
Vol 20 (12) ◽  
pp. 2774-2782 ◽  
Author(s):  
Yves Perel ◽  
Anne Auvrignon ◽  
Thierry Leblanc ◽  
Jean-Pierre Vannier ◽  
Gerard Michel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Low Dose ◽  
Disease Free Survival ◽  
High Dose ◽  
Induction Phase ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Childhood Acute Myeloid Leukemia ◽  
To Receive

PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% ± 6% and 48% ± 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% ± 19% v 50% ± 15%; P = .25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% ± 13% v 58% ± 15%; P = .04) due to a higher salvage rate after relapse. CONCLUSION: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.

scholarly journals The Influence of Cisplatin Dose upon Survival in Concurrent Chemoradiotherapy of Locally Advanced Cervical Carcinoma with Weekly Cisplatin

2008 ◽  
Vol 51 (2) ◽  
pp. 95-99 ◽  
Author(s):  
Igor Sirák ◽  
Jiří Petera ◽  
Zdeněk Zoul
Keyword(s):  
Overall Survival ◽  
Cervical Carcinoma ◽  
Concurrent Chemoradiotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Hematological Toxicity ◽  
High Dose ◽  
Free Survival ◽  
Disease Free ◽  
Weekly Cisplatin

The objective of this study was to evaluate the influence of cisplatin dose upon 3-year overall and disease-free survival rate of patients with advanced cervical cancer treated with concurrent chemoradiotherapy with weekly cisplatin. Seventy-three patients with stage IIB – IVA cervical carcinoma were treated with pelvic (or pelvic + paraaortic) externalbeam radiotherapy, high-dose rate brachytherapy and concomitant chemotherapy with weekly cisplatin of 40 mg/m2 in the time period form January 2000 to December 2006 at our department. The 3-year overall survival and disease-free suvival rates were evaluated with regard to the number of cisplatin cycles applied during the external radiotherapy. Only twentyeight patients received the intended five doses of chemotherapy. The most frequent cause of chemotherapy delay was the acute hematological toxicity with leukopenia. The 3-year overall survival was 71 % and the 3-year disease-free survival was 61 %. Survival analyses didn’t prove a statistically significant influence of cisplatin dose upon 3-year survival in cervical carcinoma patients treated by exclusive chemoradiation with weekly cisplatin.

Impact of induction chemotherapy and adjuvant radiation therapy on outcome after extrapleural pneumonectomy for malignant pleural mesothelioma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7708-7708 ◽  
Author(s):  
M. de Perrot ◽  
R. Feld ◽  
M. Anraku ◽  
A. Bezjak ◽  
R. Burkes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Induction Chemotherapy ◽  
Malignant Pleural Mesothelioma ◽  
Disease Free Survival ◽  
Extrapleural Pneumonectomy ◽  
High Dose ◽  
Pleural Mesothelioma ◽  
Free Survival ◽  
Disease Free

7708 Background: Examine the results of tri-modality therapy for malignant pleural mesothelioma (MPM). Methods: Protocol consisted of induction cisplatin-based chemotherapy, followed by extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiation therapy (RT) to 54 Gy. Results: A total of 60 patients were suitable candidates for tri-modality therapy between 01/2001 and 01/2007. Induction chemotherapy was administered to 56 patients; 4 patients underwent EPP without induction chemotherapy because of patient refusal (n=2), previous chemotherapy (n=1) and sarcomatoid MPM (n=1). Chemotherapy included vinorelbine/cisplatin (n=26), pemetrexed/cisplatin (n=26) and gemcitabine/cisplatin (n=4). EPP was performed in 47 patients; 13 patients did not undergo EPP because of tumor progression during chemotherapy (n=2), extensive chest wall involvement at surgery (n=6), or involvement of mediastinal lymph nodes at mediastinoscopy (n=5). Three patients (6%) died within 30 days of surgery. Pathological stage was II (n=6), III (n=35), and IV (n=6). Adjuvant RT was administered postoperatively to 36 patients and is ongoing in 5 patients; 6 patients did not receive adjuvant RT because of fatigue (n=5) or previous RT (n=1), and 4 patients did not complete RT up to 54 Gy. Overall survival for the 23 patients who completed the tri-modality therapy was 37% at 3 years with a median survival of 15 months. Eleven of the 23 patients had recurrence after a median of 8 months (range, 2–13 months). Recurrences were locoregional (n=2), in contralateral chest (n=3), abdomen (n=3), contralateral chest and abdomen (n=2), or pericardium (n=1). Among patients undergoing EPP, disease-free survival was longer in patients undergoing adjuvant high dose hemithoracic RT (p=0.07), in epithelial tumors (p=0.03), and in early stage (p=0.07). Overall survival was influenced by histology (p=0.007) and stage (p=0.05), but not by adjuvant high dose hemithoracic RT (p=0.5). The type of chemotherapy had no impact on disease-free and overall survival. Conclusions: Aggressive tri-modality therapy is feasible in selected patient with MPM. Adjuvant high dose hemithoracic RT can improve disease free survival and achieve good local control. No significant financial relationships to disclose.

Ten Year Follow up Analysis of the OSHO Phase III Trial (AML 96) Comparing Different Application Modes of AraC in Patients below 60 Years with Acute Myeloid Leukemia (AML): No Impact of AraCApplication Mode on Remission Rate, Toxicity, Disease-Free Survival or Overall Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2966-2966
Author(s):  
Cornelia Becker ◽  
Rainer Krahl ◽  
Antje Schulze ◽  
Georg Maschmeyer ◽  
Christian Junghanß ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Significant Difference

Abstract Clinical trials on different cytarabine doses for treatment of AML provide evidence of a dose response effect, but also for increase toxicity after high dose AraC (HDAC). Pharmacokinetic measurements of cytarabine-triphosphate (AraC-CTP), which is the most relevant cytotoxic metabolite of AraC, have revealed its formation in leukemic cells to be saturated with infusion rates above 250 mg/m2/h, this being significantly lower than used in HDAC schedules. Methods: Based on a pharmacological model and encouraging results of a phase II study we conducted a prospective randomized multicenter clinical trial comparing the effects of two different application modes of AraC in patients up to 60 years with untreated newly diagnosed AML. Patients were randomized to receive AraC at two different infusion rates (IR) during induction and consolidation treatment: arm A/experimental: 1 × 2 g/m2/d AraC over 8 hours (IR 250 mg/m2/h) arm B/standard: 2 × 1 g/m2/d AraC over 3 hours (IR 333 mg/m2/h). Induction and first consolidation consisted of AraC (days 1, 3, 5, 7) in combination with an anthracycline (Idarubicine 12 mg/m2 or Mitoxantrone 10 mg/m2, days 1–3). The final dosage points (AraC day 7 and anthracycline day 3) were excluded from the second consolidation. The third consolidation consisted of either allogeneic or autologous stem cell transplantation or of chemotherapy identical to second consolidation. Results: From 02/97 to 04/02 419 patients were enrolled in the study. The present analysis is based on 361 eligible and evaluable patients with a median follow up of 7 years. CR was reached in 249/361 (69%; 95%CI: 65%–74%) patients. No statistically significant differences were detected between arms A and B with regard to CR-rate (69% vs 69%) or early death rate (11% vs 8%). Hematological recovery of median white blood cell count (WBC) > 109/l and median platelets (plt) > 50 × 109/l revealed no difference between arms A and B after induction (WBC day 22 vs 22, p=0,68; plt day 25 vs 26, p=0,41) and consolidation (WBC day 28 vs 27, p=0,07; plt day 42 vs 40, p= 0,58). The event free survival (EFS) after 5 years is 0,25 ± 0,03 % for all patients with an overall survival of 0,31 ± 0,03 % after 5 years. For the purposes of analysis, the 83 transplant patients (23 allogeneic MRD, 14 allogeneic MUD and 46 autologous) were censored at time of transplant. No statistically significant difference between arms A and B in regard to EFS (0,25 ± 0,04 vs 0,25 ± 0,04, p=0,99), relapse incidence (0,63 ± 0,06 vs 0,60 ± 0,06, p=0,89), overall survival (0,32 ± 0,04 vs 0,30 ± 0,04, p=0,44) and therapy associated mortality (0,18 ± 0,04 vs 0,17 ± 0,03, p=0,95) were detectable after adjustment of prognostic factors. An analysis of risk factors by multivariate cox regression model confirmed cytogenetics at diagnosis to be the most important risk factor for CR rate (p<10−6) and for EFS (p<10−6). Other significant prognostic factors for EFS evaluated in the multivariate analysis were de novo vs secondary AML (p=0,0001), WBC (continuous) (p=0,001), LDH (>1–4 × vs other ULN) (p=0,008) and FAB classification (FAB M0,6,7 vs FAB M1,2,4,5) (p=0,0005). EFS after 5 years shows a significant correlation to cytogenetics (p<10−6) with 0,71±0,1, 0,27±0,05, 0,20±0,06 and 0,03±0,03 for favorable, normal, other and unfavorable cytogenetic karyotype, respectively. Conclusion: We conclude that the application of AraC at the presumptive saturating infusion rate of 250 mg/m2/h results in comparable remission rates, toxicity, event free survival and overall survival as compared to the standard IR with 333 mg/m2/h.

scholarly journals Improved Survival for Children and Young Adults With T-Lineage Acute Lymphoblastic Leukemia: Results From the Children’s Oncology Group AALL0434 Methotrexate Randomization

2018 ◽  
Vol 36 (29) ◽  
pp. 2926-2934 ◽  
Author(s):  
Stuart S. Winter ◽  
Kimberly P. Dunsmore ◽  
Meenakshi Devidas ◽  
Brent L. Wood ◽  
Natia Esiashvili ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Disease Free Survival ◽  
High Dose ◽  
Oncology Group ◽  
Cns Involvement ◽  
Free Survival ◽  
Leucovorin Rescue

Purpose Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): the Children’s Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen. Patients and Methods COG AALL0434 included a 2 × 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase. All patients with T-ALL, except for those with low-risk features, received prophylactic (12 Gy) or therapeutic (18 Gy for CNS3) cranial irradiation during either the consolidation (C-MTX; second month of therapy) or delayed intensification (HDMTX; seventh month of therapy) phase. Results AALL0434 accrued 1,895 patients from 2007 to 2014. The 5-year event-free survival and overall survival rates for all eligible, evaluable patients with T-ALL were 83.8% (95% CI, 81.2% to 86.4%) and 89.5% (95% CI, 87.4% to 91.7%), respectively. The 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia were randomly assigned to receive ABFM with C-MTX (n = 519) or HDMTX (n = 512). The estimated 5-year disease-free survival ( P = .005) and overall survival ( P = .04) rates were 91.5% (95% CI, 88.1% to 94.8%) and 93.7% (95% CI, 90.8% to 96.6%) for C-MTX and 85.3% (95% CI, 81.0%–89.5%) and 89.4% (95% CI, 85.7%–93.2%) for HDMTX. Patients assigned to C-MTX had 32 relapses, six with CNS involvement, whereas those assigned to HDMTX had 59 relapses, 23 with CNS involvement. Conclusion AALL0434 established that ABFM with C-MTX was superior to ABFM plus HDMTX for T-ALL in approximately 90% of patients who received CRT, with later timing for those receiving HDMTX.

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