levoleucovorin and Acute-Kidney-Injury

A case of acute kidney injury (AKI) strongly suspected to be drug-induced (oxaliplatin and non-steroidal anti-inflammatory drug) is discussed regarding the mechanism of a reduced glomerular filtration rate responsible for the development of AKI. Urinary biochemical tests are useful for the differential diagnosis of pre- renal (functional) AKI and intrinsic (structural) AKI(so-called acute tubular necrosis). In this case, although a comprehensive differential diagnosis using these parameters supported intrinsic AKI, only one pa- rameter, fractional excretion of urea (FEurea), indicated the existence of prerenal AKI. As a result of treatment with the appropriate management of body fluid in addition to avoiding nephrotoxic medications, AKI rapidly improved. FEurea revealed the underlying mechanism of AKI. [Review].

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Diarrhea; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Rectal Neoplasms; Vomiting

: High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m. High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m

Topics: Acute Kidney Injury; Antimetabolites, Antineoplastic; Bone Marrow; Chemical and Drug Induced Liver Injury; Crystallization; gamma-Glutamyl Hydrolase; Humans; Leucovorin; Methotrexate; Mucositis

The treatment-associated toxicity in 189 patients entered in the COSS-80 Study was analyzed. The sequential use of high-dose methotrexate (HDMTX) with citrovorum factor rescue (CFR) and cis-platinum may be additive or synergistic in causing renal toxicity. However, evaluation of the 48-h serum methotrexate level and the incidence of elevated serum creatinine levels throughout treatment failed to indicate prolonged methotrexate elimination or severe kidney damage from this regimen where an interval of 3 weeks between cis-platinum administration and the next course of HDMTX was mandatory. The treatment-related mortality was 3.2% (6 out of 189 patients). Three patients died of septicemia during chemotherapy-induced bone-marrow depression following treatment with adriamycin or the combination of bleomycin, cyclophosphamide, and dactinomycin (BCD). Three deaths occurred following the use of high-dose methotrexate with citrovorum factor rescue. Two of these deaths were associated with delayed excretion of methotrexate. The toxicity is within the range reported in the literature.

Topics: Acute Kidney Injury; Adolescent; Adult; Antineoplastic Agents; Body Weight; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Leucovorin; Leukopenia; Male; Methotrexate; Osteosarcoma

In patients exposed to high-dose methotrexate (HDMTX; >1g/m. This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 μmol/L) and incident AKI after each HDMTX dose.. The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001).. Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Topics: Acute Kidney Injury; Aged; Female; Humans; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Retrospective Studies

Topics: Acute Kidney Injury; Humans; Leucovorin; Methotrexate

High-dose methotrexate therapy (HDMTX) is a common form of chemotherapy used in children with high-grade malignancy such as osteosarcoma. Treatment with HDMTX requires careful monitoring of drug levels with folinic acid (leucovorin) rescue therapy. Toxicity from methotrexate is not uncommon and sometimes causes significant morbidity and mortality.. We report an 11-year-old child whose 24-h post-HDMTX serum level was 651.8 μmol/L (recommended level <20 μmol/L), which was complicated by septic shock and progressive renal and liver failure. As carboxypeptidase (glucarpidase) was not available locally, she was treated with the sequential use of charcoal hemoperfusion (CHP) and single-pass albumin dialysis (SPAD). The patient recovered without complications. Both liver and renal function recovered with no significant late sequelae.. CHP and SPAD are effective extracorporeal methods of removing methotrexate. They provide alternative treatment options for critical care nephrologists in the management of methotrexate toxicity.

Topics: Acute Kidney Injury; Albumins; Antidotes; Antimetabolites, Antineoplastic; Charcoal; Child; Female; Hemoperfusion; Humans; Leucovorin; Methotrexate; Renal Dialysis

Glucarpidase rapidly reduces methotrexate plasma concentrations in patients experiencing methotrexate-induced renal dysfunction. Debate exists regarding the role of glucarpidase in therapy given its high cost. The use of reduced-dose glucarpidase has been reported, and may allow more institutions to supply this drug to their patients. This report explores the relationship between glucarpidase dosage and patient outcomes in pediatric oncology patients.. The authors evaluated data from 26 patients who received glucarpidase after high-dose methotrexate. Decrease in plasma methotrexate concentrations and time to renal recovery were evaluated for an association with glucarpidase dosage, which ranged from 13 to 90 units/kg.. No significant relationship was found between glucarpidase dosage (units/kg) and percent decrease in methotrexate plasma concentrations measured by TDx (P > 0.1) or HPLC (P > 0.5). Patients who received glucarpidase dosages <50 units/kg had a median percent reduction in methotrexate plasma concentration of 99.4% (range, 98-100) measured by HPLC compared to a median percent reduction of 99.4% (range, 77.2-100) in patients who received ≥50 units/kg. Time to SCr recovery was not related to glucarpidase dosage (P > 0.8).. The efficacy of glucarpidase in the treatment of HDMTX-induced kidney injury was not dosage-dependent in this retrospective analysis of pediatric oncology patients.

Topics: Acute Kidney Injury; Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Creatinine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Costs; Drug Evaluation; Female; gamma-Glutamyl Hydrolase; Hematologic Neoplasms; Humans; Inactivation, Metabolic; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Methotrexate; Osteosarcoma; Recombinant Proteins; Recovery of Function; Retrospective Studies; Young Adult

Topics: Acute Kidney Injury; Aged; Brain; Combined Modality Therapy; Cranial Irradiation; Humans; Kidney Tubular Necrosis, Acute; Leucovorin; Lymphoma, B-Cell; Male; Metabolic Clearance Rate; Methotrexate; Recurrence; Renal Dialysis; Salvage Therapy

Because the incidence rate of renal impairment is 2-10% for patients treated with high-dose methotrexate and renal impairment develops in 0-12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination.. Pooled analysis of efficacy data from four multicenter single-arm compassionate-use clinical trials using protocols from 1993 to 2007.. Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1 μmol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement.. Efficacy was defined as rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, with a concentration of 1 μmol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20 years (range 5 weeks-84 years). Osteosarcoma (36%), non-Hodgkin lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7 μmol/L. At the first (median 15 minutes) through the last (median 40 hours) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. A total of 64% of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5 days after glucarpidase administration.. Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients.

Topics: Acute Kidney Injury; Antimetabolites, Antineoplastic; Bone Neoplasms; Compassionate Use Trials; Drug Administration Schedule; gamma-Glutamyl Hydrolase; Humans; Leucovorin; Methotrexate; Osteosarcoma; Treatment Outcome

Topics: Acute Kidney Injury; Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Fluorouracil; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Oxaliplatin

Oxaliplatin is effective in advanced colorectal cancer and is known to have relatively few side effects, such as hemolysis and renal toxicity. We report a case of acute kidney injury (AKI) after treatment with a combination of oxaliplatin, folinic acid and 5-fluorouracil or capecitabine. The patient developed acute renal failure, hemolytic anemia and thrombocytopenia after the 34th course of chemotherapy including oxaliplatin. A positive direct antiglobulin test and detection of immunoglobulin G and complement C3b and C3d on erythrocytes suggested the diagnosis of immune-related severe intravascular hemolytic anemia. She was successfully treated and recovered using plasma exchange, corticosteroids and hemodialysis therapy. Only seven other cases of AKI associated with oxaliplatin use have been reported to date. As in this case, acute hemolysis due to autoimmune mechanisms and subsequent AKI occurred suddenly after frequent use of oxaliplatin in four of those cases. We should be aware that oxaliplatin may cause sudden life-threatening hemolysis by drug-induced antibodies and subsequent AKI, even though oxaliplatin is frequently administered without side effects. This represents the first case report of AKI-related hemolysis due to oxaliplatin in Japan.

Topics: Acute Kidney Injury; Anemia, Hemolytic, Autoimmune; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colonic Neoplasms; Deoxycytidine; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prednisone; Thrombocytopenia

To describe the successful use of glucarpidase (carboxypeptidase G2) in the treatment of high-dose methotrexate-induced nephrotoxicity in a patient with osteosarcoma.. A 12-year-old female patient who had been diagnosed with low-grade right mandibular osteosarcoma was started on a protocol of cisplatin plus doxorubicin alternating with high-dose methotrexate. Following her first dose of methotrexte, she developed acute renal failure and higher than expected 24h methotrexate level of 478μM/L. High-dose leucovorin rescue was started with vigorous hydra- tion and urine alkalinization together with two sessions of hemodialysis. Because her methotrexate level was persistently high, the investigational drug glucarpidase was administered. Methotrexate level dropped from 65 to 16.3 μM/L after a single dose of glucarpidase measured by fluorescence polarization immunoassay. Leucovorin and urine alkalinization were continued until day 17 when the patient's kidney function normalized and methotrexate level reached 0.05 μM/L. The patient tolerated glucarpidase well without any significant adverse events.. Glucarpidase is a safe and effective agent in the management of high-dose methotrexate-induced nephrotoxicity and delayed methotrexate elimination.

Topics: Acute Kidney Injury; Antimetabolites, Antineoplastic; Child; Drug Therapy, Combination; Drugs, Investigational; Enzyme Therapy; Female; gamma-Glutamyl Hydrolase; Humans; Jordan; Leucovorin; Mandibular Neoplasms; Methotrexate; Osteosarcoma; Treatment Outcome; Vitamin B Complex

Acute renal failure (ARF) is one of rare and severe methotrexate (MT)-induced complications in patients with acute lymphoblastic leukemia. A case of MT-induced renal dysfunction with an extremely high serum MT concentration is reported. This toxicity required conduction of hemodiafiltration for extracorporeal MT elimination. The presence of homozygous mutation of methylene-tetrahydrofolate reductase reflects an individual metabolism of MT and its renal clearance.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Humans; Kidney Function Tests; Leucovorin; Male; Methotrexate; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction

In addition to the well-known signs of methotrexate toxicity, rare cutaneous side effects have been described. These cutaneous signs may provide a diagnostic clue into the diagnosis of toxicity as well as facilitate early and aggressive therapy. We describe the case of a 37-year-old male, with a diagnosis of psoriasis, who developed characteristic signs and symptoms of acute methotrexate toxicity after receiving an unknown amount of intravenous methotrexate. The patient experienced a distinct change in the morphology of his existing psoriatic plaques, which became ulcerated and necrotic in the week following the methotrexate injection. Shortly after the development of cutaneous erosions, the patient developed pancytopenia, which ultimately led to his death. Ulceration and necrosis of cutaneous psoriasis plaques may serve as a herald for the impending development of life-threatening pancytopenia in patients with acute methotrexate toxicity.

Topics: Acute Kidney Injury; Adult; Azithromycin; Biopsy; Fatal Outcome; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Leucovorin; Male; Methotrexate; Mucositis; Necrosis; Pancytopenia; Plasma; Psoriasis; Recombinant Proteins; Self Medication; Skin Ulcer; Trimethoprim, Sulfamethoxazole Drug Combination

Oxaliplatin is an effective chemotherapeutic agent frequently used in the treatment of colorectal carcinoma. Rare cases of renal failure and hemolytic reactions have been reported as separate side effects of oxaliplatin. Here we present a clinical picture of immune-related intravascular hemolysis and acute tubular necrosis in a patient receiving this drug. This case suggests a mechanistic explanation of renal failure in patients treated with oxaliplatin.

Topics: Acute Kidney Injury; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Colonic Neoplasms; Fluorouracil; Hemolysis; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Prognosis

A 10-year-old boy with osteosarcoma and normal renal function manifested laboratory evidence of impending renal toxicity and extreme elevation of aspartate aminotrasferase and alanine aminotransferase within 2 hours after the completion of a 4-hour infusion of high-dose methotrexate (MTX) (12 g/m2), and went on to develop acute renal failure with life-threatening hyperkalemia 29 hours later. Although his renal function recovered completely with high-dose leucovorin, hemodialysis, charcoal hemoperfusion, and carboxypeptidase G2, we present this case to emphasize that signs of renal toxicity may be present as early as 2 hours after the completion of a 4-hour MTX infusion, and to suggest that monitoring for MTX toxicity should perhaps begin within a few hours after the completion of 4-hour MTX infusion.

Topics: Acute Kidney Injury; Antimetabolites, Antineoplastic; Bone Neoplasms; Child; Drug Monitoring; gamma-Glutamyl Hydrolase; Humans; Leucovorin; Male; Methotrexate; Osteosarcoma

Topics: Acute Kidney Injury; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Infusions, Intravenous; Leucovorin; Methotrexate; Migraine Disorders; Oxazolidinones; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Serotonin Receptor Agonists; Tryptamines

A 56-year-old man was hospitalized for evaluation of left neck tumor. The biopsy of neck lymph node showed a squamous cell carcinoma. Since no primary lesion was detected, the diagnosis was primary unknown neck lymph node metastasis. The first course of our chemotherapeutic regimen consisted of CDDP, 5-FU, MTX and LV. After MTX infusion, the level of serum creatinine increased. Based on laboratory data, we diagnosed acute renal failure caused by MTX and added the infusion of Ringer and LV. The serum creatinine level decreased to the level before chemotherapy. In the second course, chemotherapy with only CDDP and 5-FU was administered, and the level of serum creatinine did not increase. In the present case, suitable intravenous drip infusion of Ringer's injection prevented irreversible renal dysfunction. Since the laboratory data did not show dysfunction of uriniferous tubule and renal glomerulus, we considered allergic nephritis as a possibility.

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Fluorouracil; Head and Neck Neoplasms; Humans; Leucovorin; Lymph Nodes; Lymphatic Metastasis; Male; Methotrexate; Middle Aged

Acute renal failure induced by methotrexate (MTX) can be lethal because renal excretion of the drug can be delayed. Pre-existing renal impairment, abstention, or underdosage of folinic acid and inadequate hydration facilitate toxicity. The prolonged high serum levels of MTX result in severe mucositis and pancytopenia, but strategies useful to accelerate MTX removal have not been universally accepted. We report a case of a 13-year-old girl with osteosarcoma who was treated with high-dose MTX because of thoracic tumor recurrence. No side effects were observed after 2 cycles of high-dose MTX; however, after the third cycle there was a delayed MTX elimination followed by clinical toxicity. Forty hours post-MTX infusion the serum level of MTX was 5.39 x 10(-4) mol/L. Treatment was based on symptomatic measures, such as maintenance of an abundant and alkaline diuresis and parenteral administration of folinic acid. Concomitantly, plasma exchange was employed to accelerate MTX removal and reduce its toxicity. After 24 days, she was discharged from the hospital, and her renal function recovered gradually.

Topics: Acute Kidney Injury; Adolescent; Antimetabolites, Antineoplastic; Diuresis; Female; Femoral Neoplasms; Humans; Leucovorin; Methotrexate; Osteosarcoma; Plasma Exchange; Thoracic Neoplasms

A 54-year-old patient with primary cerebral lymphoma was treated with two 4-weekly cycles of high-dose intravenous cytarabine (12 g/m2) and methotrexate (3 g/m2). The administration of the first course proceeded without notable complications. Before the administration of methotrexate in the second cycle blood cell counts and chemistry showed no abnormalities except for slightly increased alkaline phosphatase and gamma-glutamyl-transpeptidase levels which was attributed to diphantoin comedication. The patient developed symptoms of acute renal failure 7 h after methotrexate infusion which resulted in a very high serum methotrexate level (39.84 micromol/l) at 20 h after infusion. Rescue therapy was intensified: the leucovorin dosage was increased (1,200 mg continuous i.v. infusion every 24 h) and combined with thymidine rescue therapy (8 g/m2 per day continuous i.v. infusion every 24 h). Urine alkalinization was increased and diphantoin therapy was stopped. Leucovorin eye drops and mouth washes were started 5 days after methotrexate administration to prevent conjunctivitis and mucositis as a result of high methotrexate levels (>2.4 micromol/l). In spite of the fact that serum methotrexate levels remained persistently higher than 0.1 micromol/l for 12 days, the patient experienced no further short-term systemic toxicity except for anaemia (grade 3 according to NCI Common Toxicity Criteria). After day 12 intensified rescue therapy and the frequency of alkalinization were decreased to standard procedures and stopped on day 19. It is concluded that i.v. administration with high-dose methotrexate can result in unpredictable acute toxicity. In our patient, acute methotrexate toxicity was treated successfully by intensification of classical leucovorin rescue therapy in combination with thymidine infusion. In addition, leucovorin mouth washes and eye drops may have prevented mucositis and conjunctivitis, respectively.

Topics: Acute Kidney Injury; Antimetabolites, Antineoplastic; Brain Neoplasms; Drug Therapy, Combination; Humans; Leucovorin; Lymphoma; Methotrexate; Middle Aged; Thymidine

We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.

Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Diseases; Bone Marrow Purging; Cardiomyopathies; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Cyclophosphamide; Cystitis; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Infections; Leucovorin; Life Tables; Lymphoma, Non-Hodgkin; Male; Melphalan; Methotrexate; Middle Aged; Mitoxantrone; Pilot Projects; Salvage Therapy; Survival Analysis; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

A 79 year-old female patient presented with immunoblastic B-cell lymphoma of the ethmoidal sinuses and destruction of the anterior cranial fossa. After 3 cycles of high-dose methorexate (HD-MTX) MTX serum level remained elevated and creatinine serum levels raised. The patient received Carboxypeptidase G2 (CPG2) intravenously. Within one hour the MTX serum level decreased to <1 micromol/l as determined by high pressure liquid chromatography (HPLC). The patient recovered without significant toxicity and attained a long lasting ongoing (>14 months) complete remission. In this case we were able to demonstrate that rescue from HD-MT nephrotoxicity by CPG2 is also safe and effective in patients with advanced age with impaired renal function. With the help of CPG2, sufficient and potentially curative therapy with HD-MTX may also be provided to patients with a high risk of renal failure.

Topics: Acute Kidney Injury; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bacterial Proteins; Carmustine; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Diuretics; Doxorubicin; Ethmoid Sinus; Female; Fluid Therapy; Folic Acid; Furosemide; gamma-Glutamyl Hydrolase; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Large-Cell, Immunoblastic; Methotrexate; Paranasal Sinus Neoplasms; Prednisone; Procarbazine; Remission Induction; Vincristine

We describe the case of a 35-year old male who developed acute renal failure following high dose methotrexate therapy for Burkitt's non Hodgkin lymphoma. Serum methotrexate levels reached 37 micromol/l, and remained higher than 1 micromol/l for more than a week. Folinic acid rescue was intensified to 200-400 mg intravenously every 4 hours. As methotrexate binds markedly to proteins, plasma exchange was initially chosen, 4 sessions being performed from day 2 to day 4. The methotrexate pharmacokinetic profile was not significantly modified during plasma exchange, and serum drug level was 3 micromol/l. Continuous veno-venous hemodiafiltration was therefore performed from day 5 to day 10. This procedure also seemed ineffective, with evidence of low ultrafiltrate clearance. No extrarenal toxicity was observed in our patient. Thus, conventional extrarenal procedures appear to have a limited role in the setting of overexposure to methotrexate. The use of very high doses of folinic acid in our case probably played a major role in the eventual favorable outcome.

Topics: Acute Kidney Injury; Adult; Antidotes; Burkitt Lymphoma; Dose-Response Relationship, Drug; Humans; Leucovorin; Male; Methotrexate

We report on a case of methotrexate (MTX) intoxication occurring in a 19-year-old man treated for a leukemia. Exchange-transfusion (ET) was performed in attempt to remove the MTX from the body. This exchange-transfusion was unable to decrease the MTX plasma concentration. This inefficacy of ET in MTX intoxication is in contradiction with previously reported recommendations. However, this result is easily explained by MTX pharmacokinetics parameters.

Topics: Acute Kidney Injury; Adult; Antidotes; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Diuretics; Drug Overdose; Exchange Transfusion, Whole Blood; Furosemide; Humans; Leucovorin; Male; Methotrexate; Pancytopenia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Treatment Failure

Methotrexate toxicity is rare but extremely severe. When complete, it consists of ulcerations of the gastrointestinal mucosae responsible for necrotizing enteritis, erythroderma, bone marrow aplasia, interstitial pneumonia, hepatitis and organic renal failure with diuresis. Toxicity is facilitated by pre-existing renal impairment, third sector and abstention or underdosage of foliculinic acid prescribed as antagonist. The diagnosis rests on serum assays, the results of which must be interpreted taking into account the assay method and the time elapsed between the injection of methotrexate and its assay in serum. The multivisceral pathology observed may totally regress, as in the case reported here. Treatment is based on symptomatic measures, starting with maintenance of an abundant and alkaline diuresis, and on the parenteral administration of folinic acid in doses that vary with the authors.

Topics: Acute Kidney Injury; Chemical and Drug Induced Liver Injury; Dermatitis, Exfoliative; Enteritis; Femoral Neoplasms; Humans; Leucovorin; Male; Methotrexate; Middle Aged; Osteosarcoma; Poisoning; Pulmonary Fibrosis

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Combined Modality Therapy; Drug Interactions; Female; Humans; Iopamidol; Leucovorin; Lymphoma; Male; Methotrexate; Middle Aged; Osteosarcoma

Topics: Acute Kidney Injury; Adolescent; Humans; Leucovorin; Male; Methotrexate; Osteosarcoma