scholarly journals Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404)

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 874-883 ◽  
Author(s):  
Barbara L. Asselin ◽  
Meenakshi Devidas ◽  
Chenguang Wang ◽  
Jeanette Pullen ◽  
Michael J. Borowitz ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Randomized Study ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Oncology Group ◽  
Dose Methotrexate ◽  
Increased Risk ◽  
The Difference

Abstract The Pediatric Oncology Group (POG) phase 3 trial 9404 was designed to determine the effectiveness of high-dose methotrexate (HDM) when added to multi-agent chemotherapy based on the Dana-Farber backbone. Children with T-cell acute lymphoblastic leukemia (T-ALL) or advanced lymphoblastic lymphoma (T-NHL) were randomized at diagnosis to receive/not receive HDM (5 g/m2 as a 24-hour infusion) at weeks 4, 7, 10, and 13. Between 1996 and 2000, 436 patients were enrolled in the methotrexate randomization. Five-year and 10-year event-free survival (EFS) was 80.2% ± 2.8% and 78.1% ± 4.3% for HDM (n = 219) versus 73.6% ± 3.1% and 72.6% ± 5.0% for no HDM (n = 217; P = .17). For T-ALL, 5-year and 10-year EFS was significantly better with HDM (n = 148, 5 years: 79.5% ± 3.4%, 10 years: 77.3% ± 5.3%) versus no HDM (n = 151, 5 years: 67.5% ± 3.9%, 10 years: 66.0% ± 6.6%; P = .047). The difference in EFS between HDM and no HDM was not significant for T-NHL patients (n = 71, 5 years: 81.7% ± 4.9%, 10 years: 79.9% ± 7.5% vs n = 66, 5 years: 87.8% ± 4.2%, 10 years: 87.8% ± 6.4%; P = .38). The frequency of mucositis was significantly higher in patients treated with HDM (P = .003). The results support adding HDM to the treatment of children with T-ALL, but not with NHL, despite the increased risk of mucositis.

scholarly journals High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia

2018 ◽  
Vol 10 ◽  
pp. 44-51 ◽  
Author(s):  
Wasil Jastaniah ◽  
Naglla Elimam ◽  
Khalid Abdalla ◽  
Aeshah A. AlAzmi ◽  
Mohammed Aseeri ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Cell Acute Lymphoblastic Leukemia

Intussusception in Childhood Acute T Cell Lymphoblastic Leukemia: An Unusual Complication - Report of 2 Cases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4530-4530
Author(s):  
Jesika Shah ◽  
Dan Barlev ◽  
Arlene Sara Redner ◽  
Ashok Shende ◽  
Gungor Karayalcin
Keyword(s):  
Abdominal Pain ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Rare Complication ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Consolidation Chemotherapy ◽  
Gastrointestinal Complications ◽  
Dose Methotrexate ◽  
Descending Colon

Abstract Clinically significant gastrointestinal complications in children with acute lymphoblastic leukemia (ALL) have been reported. However, intussusception is a very rare complication. In one study of 286 children with ALL gastrointestinal complications occurred in 5.6% of patients with intussusception seen in only 0.3% of patients. We describe two cases of intussusception during chemotherapy for T-cell leukemia. Patient #1 was an 8 year old girl on chemotherapy for T-cell ALL. Around week 9 following POG 9404 protocol of consolidation chemotherapy, patient presented with severe abdominal pain and vomiting, and had marked, diffuse tenderness of the abdomen with guarding and hypo-active bowel sounds. Abdominal radiograph showed thickening of the descending colon; abdominal sonogram was normal; abdominal computed tomography (CT) scan however, revealed a soft tissue and fluid-filled mass extending from the cecum to the descending colon. These findings were consistent with a large bowel intussusception, which was successfully reduced with a barium enema. Patient #2 was a 15 year old male receiving chemotherapy for T-cell ALL following POG 9404 protocol. At week 14 of consolidation chemotherapy, patient presented with a 2 day history of nausea and colicky peri-umbilical and right lower quadrant abdominal pain. An abdominal CT scan revealed an ileocolic intussusception without bowel obstruction and mild wall thickening of the cecum. Barium enema resulted in successful reduction of the intussusception. Interestingly, both our patients were treated with high dose methotrexate 5gm/m2 during this time period and both experienced delayed excretion of methotrexate. To our knowledge, there is no known reported association between high dose methotrexate and intussusception. We speculate that the two could be related. The increased use of high dose methotrexate therapy in T-cell ALL may result in a higher incidence of intussusception in this population. Although, intussusception in ALL is a very rare complication, awareness of this entity and early recognition with radiological intervention may prevent unnecessary surgery and the associated morbidity and mortality in these patients.

High-Dose Methotrexate and Early Intensification of Therapy Do Not Improve 3 Year EFS in Children and Adolescents with Disseminated Lymphoblastic Lymphoma. Results of the Randomized Arms of COG A5971

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3610-3610 ◽  
Author(s):  
Minnie Abromowitch ◽  
Amanda Termuhlen ◽  
Myron Chang ◽  
Sherrie L. Perkins ◽  
Thomas Gross ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymphoblastic Leukemia ◽  
Bone Marrow Involvement ◽  
Disease Free Survival ◽  
Lymphoblastic Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cns Disease ◽  
Dose Methotrexate ◽  
Significant Difference

Abstract The treatment of pediatric lymphoblastic lymphoma (LL) has developed in parallel with treatment strategies for childhood acute lymphoblastic leukemia using a BFM backbone. The excellent results of the NHL/BFM 90 trial prompted us to design this randomized factorial study to determine whether a regimen without high dose methotrexate (HDMTX) the CCG BFM will result in the same outcome as NHL/BFM-90 and whether intensification with anthracycline and cyclophosphamide would further improve disease free survival. From June 2000 to October 2005, 257 patients with Murphy’s Stage III and IV (excluding CNS disease) LL were randomized to one of the four regimens. All regimens used the BFM/NHL95 backbone. The CCG BFM regimen had intrathecal (IT) methotrexate throughout interim maintenance and maintenance without IV methotrexate. The NHL BFM utilized I.V. Methotrexate 5 Gms/m2 and intrathecal MTX every 2 weeks for four doses during interim maintenance without further intrathecal MTX during maintenance. One of each backbone regimens was further intensified with anthracycline and cyclophosphamide early in induction and delayed intensification. The median age was 10.3 years, 195 (76%) were males; 43 (17%) had >5% bone marrow involvement. Twelve patients with CNS disease were not randomized and received intensification and HD HDMTX with delayed CNS radiation (data not reported here). Major toxicities have been related to bone marrow suppression with 4 toxic deaths, 3 due to sepsis and 1 from cerebral hemorrhage. The frequency of grade III/IV neutropenia (alone, with fever or with infection), anemia, and thrombocytopenia were higher in the intensified arms during induction. Three of the four toxic deaths occurred on the intensified arms. The three years EFS of the HDMTX vs. none is 84.5% ± .3.5% vs. 82.7± 3.8 (ρ= 0.93) and the intensification vs. none is 83.4% ±3.7 vs 83.0% ± 3.6 (ρ= 0.66). Therefore, there was no significant difference between treatment arms. These results suggest that neither HDMTX nor early intensification improves EFS in LL. Future direction should focus on identifying biological factors early in therapy so alternative therapies may be investigated.

scholarly journals Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232

2016 ◽  
Vol 34 (20) ◽  
pp. 2380-2388 ◽  
Author(s):  
Eric C. Larsen ◽  
Meenakshi Devidas ◽  
Si Chen ◽  
Wanda L. Salzer ◽  
Elizabeth A. Raetz ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Dose Methotrexate ◽  
Children And Young Adults

Purpose Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children’s Oncology Group study AALL0232 tested two interventions to improve survival. Patients and Methods Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1. Results Planned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis. Conclusion High-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older.

scholarly journals Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

2021 ◽  
Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Optimal Dosage ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Antileukemic Effect ◽  
Folinic Acid Rescue ◽  
High Doses

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

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