High-Dose Methotrexate, Ifosfamide, Etoposide and Dexamethasone (MIED) Is an Active Salvage Regimen for Children with Recurrent or Refractory Malignant Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3434-3434
Author(s):  
John T. Sandlund ◽  
Ching-Hon Pui ◽  
Yinmei Zhou ◽  
Eric J. Lowe ◽  
Sue C. Kaste ◽  
...  
Keyword(s):  
Malignant Lymphoma ◽  
Hodgkin Lymphoma ◽  
Large Cell ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Salvage Regimen ◽  
Hematopoietic Stem ◽  
Not Otherwise Specified ◽  
Dose Methotrexate ◽  
Disease Free

Abstract Significant advances have been made in the treatment of malignant lymphomas in children; however, approximately 20–30% will have refractory or recurrent disease. These patients are felt to have a relatively poor prognosis primarily because of the comprehensive and intensive nature of their frontline therapies; therefore, they are generally considered for a novel or more aggressive salvage regimen. The purpose of this study is to determine the activity and toxicity profile of the MIED regimen (high-dose methotrexate, ifosfamide, etoposide and dexamethasone) in children with refractory or recurrent non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). From 1991 to 2006, 62 children with refractory/recurrent NHL (n=24) and HL (n=38) were treated with 1 to 6 sequential cycles of MIED (methotrexate, 8 grams/m2 on day 1; ifosfamide, 2 grams/m2 on days 2–4; etoposide, 200 mg/m2 on days 2–4; and dexamethasone, 40 mg/m2 on days 1–4). Children with NHL also received intrathecal MHA (methotrexate, hydrocortisone, and cytarabine at age adjusted dosages) on day 1. Response evaluation was performed after 1 – 2 cycles of MIED. Children with either a PR or CR were considered for an intensification phase with hematopoietic stem cell transplantation (HSCT); patients with HL also received involved-field irradiation. Forty-six (75%) of the 61 evaluable children with refractory or recurrent lymphoma responded to MIED (CR, 23; PR, 23). Among the 24 children with NHL (large cell, 18 [anaplastic large cell, 8; diffuse large B-cell, 3; T-cell large cell, 2; large cell not otherwise specified, 5]; Burkitt, 3; lymphoblastic, 2; other, 1), responses included: CR (n=10), and PR (n=5) for a combined CR+PR rate of 63%. Among the 37 children with HL (nodular sclerosis, n = 29; mixed cellularity, n =4; lymphocyte predominant, n =1; and HL not otherwise specified, n=3) responses included: CR (n=13), and PR (n=18) for a combined CR+PR rate of 84% among 37 evaluable patients. MIED was generally well tolerated (associated with grade IV hematologic toxicity in most cases and frequently associated with mucositis and/or fever with neutropenia). Nineteen of 24 children with NHL and 31 of 37 children with HL received an intensification phase with HSCT support (autologous, 46; allogeneic, 4) at some point following MIED therapy. Nine of 24 children (38%) with NHL are alive and disease-free. Twenty-eight of 37 children (76%) with HL are currently alive (24 disease-free post HSCT). MIED is an active and generally well tolerated regimen for children with refractory or recurrent malignant lymphoma.

Treatment of Systemic Primary Cutaneous Anaplastic Large Cell Lymphoma with High-Dose Methotrexate and Leucovorin Rescue.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4756-4756
Author(s):  
Reema Batra ◽  
James Boyer ◽  
Thomas O’Connor ◽  
Imad Tabbara
Keyword(s):  
Hepatitis C ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Large Cell ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Leucovorin Rescue ◽  
Large Cell Lymphoma ◽  
Pet Scans

Abstract A 59 year-old Caucasian male with a history of hepatitis C infection, presented in October 2003 with a painless skin lesion on his back. Physical examination revealed a 3 cm lesion on the back that resembled a sebaceous cyst, with similar lesions on the anterior aspects of both legs. A right inguinal lymph node was palpated as well, measuring approximately 2 cm. A wide surgical resection was performed on the back lesion due to its extensive nature at the time of surgery. Pathologic evaluation revealed a primary cutaneous anaplastic large cell lymphoma, measuring 12 cm x 5 cm in size. Immunohistochemical staining showed reactivity for CD30, CD3, UCHL-1, CD43 and CD45. Despite being asymptomatic, the patient had widespread disease on CT/PET scans, including diffuse lymphadenopathy, bony disease, and lung lesions. The patient was treated with weekly high-dose methotrexate at 2 grams/m2 followed by leucovorin rescue for cycle 1 and dose-reduced for cycles 2 through 5 to 1 gram/m2 secondary to myelosuppression. For cycles 6 through 10, the patient was able to tolerate the original dose of 2 grams/m2. After eight cycles, the patient had complete resolution of all disease by clinical examination and by CT/PET scans, and has remained in complete remission since February 2004. The patient tolerated the chemotherapy well with myelosuppression being the most significant toxicity. He also had a transient increase in his liver enzymes after cycle 1 that resolved spontaneously. He is currently being treated for reactivation of hepatitis C with pegylated interferon and ribavirin. To the best of our knowledge, this is the first case of primary cutaneous anaplastic large cell lymphoma with systemic involvement being treated successfully with weekly high-dose methotrexate and leucovorin rescue with prolonged complete remission. Weekly high-dose methotrexate with leucovorin rescue is an active and well-tolerated regimen with limited side effects.

scholarly journals The influence of folate pathway polymorphisms on high-dose methotrexaterelated toxicity and survival in children with non-Hodgkin malignant lymphoma

2014 ◽  
Vol 48 (3) ◽  
pp. 289-292 ◽  
Author(s):  
Nina Erculj ◽  
Barbara Faganel Kotnik ◽  
Marusa Debeljak ◽  
Janez Jazbec ◽  
Vita Dolzan
Keyword(s):  
T Cell ◽  
Malignant Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Wild Type ◽  
Non Hodgkin Lymphoma ◽  
Dose Methotrexate ◽  
Folate Pathway ◽  
677T Allele

Abstract Background. We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL). Patients and methods. In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms. Results. Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype. Conclusions. Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTXrelated toxicity in children with NHL.

Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD).

1983 ◽  
Vol 1 (2) ◽  
pp. 91-98 ◽  
Author(s):  
A T Skarin ◽  
G P Canellos ◽  
D S Rosenthal ◽  
D C Case ◽  
J M MacIntyre ◽  
...  
Keyword(s):  
Remission Rate ◽  
New Combination ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Prior Therapy ◽  
Dose Methotrexate ◽  
The Central Nervous System ◽  
Disease Free ◽  
Free Rate

A new combination chemotherapy program (M-BACOD) was administered to 101 patients with advanced diffuse histiocytic and diffuse undifferentiated lymphoma (DHL and DUL). High dose methotrexate (M) 3 g/m2 with leucovorin factor rescue was given on day 14 between cycles of bleomycin (B), adriamycin (A), cyclophosphamide (C), oncovin (O), and dexamethasone (D) administered every 3 weeks for 10 cycles. The complete remission rate (CR) was 72% in all 101 patients or 77% in 95 evaluable patients. The median follow-up is 3 yr 2 mo with one-third of CR patients followed beyond 4 yr. Twenty-six percent of CR patients have relapsed with a projected 5-yr survival rate of 80% (5-yr disease-free rate 65%). The overall survival of all 101 study patients reaches a plateau at 59% projected out to 5 yr. Patients with prior therapy had a significantly lower CR rate than those without prior treatment (p = 0.001); however, no other unfavorable prognostic characteristics could be identified. Relapse in the central nervous system CNS occurred in only 5.4% of CR patients. M-BACOD results in prolonged survival and possible cure in a high proportion of all patients with DHL and DUL.

High-dose methotrexate monotherapy followed by radiation for CD30-positive, anaplastic lymphoma kinase-1–positive anaplastic large-cell lymphoma in the brain of a child

2014 ◽  
Vol 14 (3) ◽  
pp. 311-315 ◽  
Author(s):  
Kazuhide Furuya ◽  
Shigehiko Takanashi ◽  
Akiko Ogawa ◽  
Yoshihisa Takahashi ◽  
Tadayoshi Nakagomi
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Anaplastic Lymphoma Kinase ◽  
Cell Lymphoma ◽  
Large Cell ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Anaplastic Lymphoma ◽  
Dose Methotrexate ◽  
Large Cell Lymphoma ◽  
The Brain

The authors report the case of an 11-year-old immunocompetent boy with primary CNS CD30-positive anaplastic large-cell lymphoma (ALCL) that was also positive for anaplastic lymphoma kinase-1. His initial clinical manifestation was acute meningitis of unknown etiology. Findings on CT scanning were normal. Although he received empirical treatment against infection, his systemic and neurological status deteriorated. Subsequent MRI revealed newly emerged enhanced lesions and concomitant edema in the left parietal lobe. Diagnosis was confirmed following a brain biopsy and immunohistochemical staining. Three courses of systemic high-dose methotrexate (HD-MTX) treatment with 2-week intervals was started, followed by whole-brain radiation. His clinical course improved, and he has remained disease-free for more than 8 years without any additional treatment. Because ALCL originating in the brain is extremely rare and difficult to diagnose, no standard treatment has been established. This report suggests that systemic HD-MTX monotherapy can be an effective and worthwhile tailored therapeutic option for pediatric primary CNS ALCL.

scholarly journals Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Suying Lu ◽  
Xiaoqin Zhu ◽  
Wei Li ◽  
Huimou Chen ◽  
Dalei Zhou ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Oral Mucositis ◽  
Methylenetetrahydrofolate Reductase ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Mutant Genotype ◽  
Non Hodgkin Lymphoma ◽  
Dose Methotrexate

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

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