Life-threatening Hypercalcemia as the First Manifestation of Acute Lymphoblastic Leukemia

2019 ◽  
Vol 56 (11) ◽  
pp. 972-974 ◽  
Author(s):  
Kakali Roy ◽  
Rajni Sharma ◽  
Manisha Jana ◽  
Vandana Jain
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Life Threatening

scholarly journals Decreased Vision as Initial Presenting Symptom of Acute Lymphoblastic Leukemia: A Case Report

2016 ◽  
Vol 7 (2) ◽  
pp. 377-383 ◽  
Author(s):  
Christoph Palme ◽  
Nikolaos E. Bechrakis ◽  
Martin Stattin ◽  
Gertrud Haas ◽  
Claus Zehetner
Keyword(s):  
Bone Marrow ◽  
Case Report ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Biopsy ◽  
Vision Loss ◽  
Lymphoblastic Leukemia ◽  
Interdisciplinary Approach ◽  
Crucial Importance ◽  
Hematologic Disorders ◽  
Life Threatening

This case illustrates that hematologic disorders must be considered as a potentially life-threatening cause for vision loss. Proper laboratory workup and timely interdisciplinary approach are essential to ensure the best possible care for ophthalmic patients. Historically, before the use of bone marrow biopsy, the ophthalmologist was often asked to assist in the diagnosis of leukemia. Since ophthalmological symptoms may be the initial presenting signs of leukemia as highlighted in this case, the ophthalmogist is still of crucial importance.

scholarly journals Personalized Treatment of 6-Mercaptopurine in Thai Children with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 1 (1) ◽  
pp. 23-27
Author(s):  
Jassada Buaboonnam ◽  
Kleebsabai Sanpakit ◽  
Trai Tharnpanich
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphism ◽  
Clinical Studies ◽  
Deoxyribonucleic Acid ◽  
Lymphoblastic Leukemia ◽  
Acid Synthesis ◽  
Special Focus ◽  
Thiopurine Methyltransferase ◽  
Deoxyribonucleic Acid Synthesis ◽  
Life Threatening

Thanks to its ability to inhibit deoxyribonucleic acid synthesis, 6-mercaptopurine (6-MP), is one of the indispensable medications for acute lymphoblastic leukemia (ALL) patients. Nevertheless, some patients may succumb to myelotoxicity, leading to treatment disruption or even life-threatening events. Owing to the advances in pharmacogenomics, the genetic polymorphism of genes regulating purine synthesis has been identified and physicians can adjust the dose of 6-MP according to each polymorphism. Such polymorphisms genetically vary among ethnicities. In this article, 2 genetic polymorphisms, namely thiopurine methyltransferase and Nudix (nucleoside diphosphate linked moiety X) type motif 15, are clinically discussed, with a special focus on the clinical studies in Thai children with ALL.

scholarly journals Crisis management in the treatment of childhood acute lymphoblastic leukemia: putting right what can go wrong (emergency complications of disease and treatment)

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 251-258 ◽  
Author(s):  
Rachael Hough ◽  
Ajay Vora
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Tumor Lysis Syndrome ◽  
Treatment Delays ◽  
Life Threatening ◽  
Pediatric All ◽  
Short And Long Term ◽  
Dose Reductions ◽  
Related Mortality

AbstractThe improvement in overall survival in children with acute lymphoblastic leukemia (ALL) over the last 5 decades has been considerable, with around 90% now surviving long term. The risk of relapse has been reduced to such an extent that the risk of treatment-related mortality is now approaching that of mortality caused by relapse. Toxicities may also lead to the suboptimal delivery of chemotherapy (treatment delays, dose reductions, dose omissions), potentially increasing relapse risk, and short- and long-term morbidity, adding to the “burden of therapy” in an increasing number of survivors. Thus, the need to reduce toxicity in pediatric ALL is becoming increasingly important. This work focuses on the risk factors, pathogenesis, clinical features, and emergency management of the life-threatening complications of ALL at presentation and during subsequent chemotherapy, including leucostasis, tumor lysis syndrome, infection, methotrexate encephalopathy, thrombosis, and pancreatitis. Potential strategies to abrogate these toxicities in the future are also discussed.

scholarly journals Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia

2020 ◽  
Vol 21 (20) ◽  
pp. 7685
Author(s):  
Fátima Bayón-Calderón ◽  
María L. Toribio ◽  
Sara González-García
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Malignant Disease ◽  
Lymphoblastic Leukemia ◽  
Antigen Receptors ◽  
Challenges And Opportunities ◽  
Life Threatening ◽  
Cell Acute Lymphoblastic Leukemia ◽  
T Cell Immunodeficiency ◽  
T Cell Malignancies

T-cell acute lymphoblastic leukemia (T-ALL), a T-cell malignant disease that mainly affects children, is still a medical challenge, especially for refractory patients for whom therapeutic options are scarce. Recent advances in immunotherapy for B-cell malignancies based on increasingly efficacious monoclonal antibodies (mAbs) and chimeric antigen receptors (CARs) have been encouraging for non-responding or relapsing patients suffering from other aggressive cancers like T-ALL. However, secondary life-threatening T-cell immunodeficiency due to shared expression of targeted antigens by healthy and malignant T cells is a main drawback of mAb—or CAR-based immunotherapies for T-ALL and other T-cell malignancies. This review provides a comprehensive update on the different immunotherapeutic strategies that are being currently applied to T-ALL. We highlight recent progress on the identification of new potential targets showing promising preclinical results and discuss current challenges and opportunities for developing novel safe and efficacious immunotherapies for T-ALL.

Successful Treatment of Refractory Acute Lymphoblastic Leukemia with Tisagenlecleucel in the Setting of Life-Threatening Infection

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5125-5125
Author(s):  
Keith J August ◽  
Terrie Flatt ◽  
Erin Marie Hall ◽  
Doug Myers
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Bone Marrow Aspirate ◽  
Lymphoblastic Leukemia ◽  
Severe Neutropenia ◽  
Active Infection ◽  
Post Infusion ◽  
Life Threatening ◽  
Cell Acute Lymphoblastic Leukemia

Tisagenlecleucel is a CD19 directed immunotherapy approved for the treatment of young patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL). The most important toxicity related to tisagenlecleucel therapy is cytokine release syndrome (CRS). CRS is an exaggerated systemic inflammatory response that occurs frequently along with T-cell expansion following the administration of tisagenlecleucel. Tisagenlecleucel guidelines recommend delaying treatment when an active infection is present due to the concern that the pre-existing inflammatory response associated with infection may predispose patients to severe CRS. We describe two cases where tisagenlecleucel was successfully administered to patients in the setting of life-threatening infection. Patient 1 is a 23-year-old Caucasian male with refractory Philadelphia chromosome negative B-cell ALL who had received prior treatment with chemotherapy, blinatumomab, inotuzumab ozogamicin and a haploidentical stem cell transplant (SCT) followed by multiple Zalmoxis infusions. Five months following SCT he relapsed. At relapse, he underwent leukapheresis followed by bridging chemotherapy with ifosfamide and etoposide. He developed severe neutropenia and respiratory failure associated with a right lower lung consolidation. A biopsy demonstrated a mucormycosis infection and he required surgical debridement including resection of portions of the lung, diaphragm and liver. At this time, he had 92% blasts in the bone marrow. Eleven days after his surgery he received tisagenlecleucel despite being persistently febrile. Prior to the infusion, he received a modified lymphodepleting chemotherapy regimen including two days of fludarabine and cytarabine. Due to severe neutropenia, he was receiving granulocyte transfusions. These were discontinued prior to the infusion and resumed after 12 days. CRP and ferritin the day prior to infusion were 26.2 mg/dL and 18,419 ng/mL. He remained persistently febrile for 13 days post-infusion. He received a single dose of tociluzimab 7 days following his infusion due to high fevers. He did not require any treatment with corticosteroids for CRS. The absolute neutrophil count recovered to >500x103/µL at 31 days post infusion. A bone marrow aspirate done 26 days post-infusion did not show any evidence of leukemia by multicolor flow cytometry (MFC). He remains alive without evidence of disease 11 months after treatment with tisagenlecleucel. Patient 2 is a 4-year-old Hispanic female with refractory B-cell ALL found to have a TP53 deletion and t(1;19). She had received prior treatment with chemotherapy, blinatumomab and local radiation therapy to the site of extramedullary disease found in the left maxillary sinus at relapse. She underwent leukapheresis and received bridging chemotherapy with mercaptopurine and methotrexate. After 3 days of lymphodepleting chemotherapy she developed septic shock and E. Coli bacteremia. She became severely ill requiring continuous renal replacement therapy for 5 days and extracorporeal membrane oxygenation (ECMO) for 6 days. Shortly after ECMO decannulation she developed fever and was found to have multiple pulmonary opacities concerning for fungal infection. Blasts were noted in the peripheral blood. Sixteen days after presenting with septic shock and 11 days from ECMO she received tisagenlecleucel. CRP at the time of infusion was 22.9 mg/dL. She developed persistent fevers post-infusion for 17 days. She received two doses of tociluzimab 20- and 21-days post-infusion due to recurrence of high fever and reactive lymphadenopathy with third spacing and concern for renovascular compromise. She did not require any treatment with corticosteroids for CRS. Bone marrow aspirate done 32 days post-infusion did not show any evidence of leukemia by MFC. The absolute neutrophil count recovered to >500x103/µL at 59 days post infusion. The patient remained without evidence of disease for 7 months following treatment but died due to infectious complications with persistent pancytopenia. Tisagenlecleucel is a potentially life-saving treatment for relapsed and refractory B-cell acute lymphoblastic leukemia in children and young adults 24 years of age or younger. Tisagenlecleucel is an option for the treatment of patients with active infection and/or inflammation with progressive leukemia when no other therapeutic alternative exists. Disclosures August: Novartis Pharmaceuticals: Speakers Bureau. Myers:Novartis Pharmaceuticals: Consultancy, Speakers Bureau.

scholarly journals Case Report: The Use of Intravenous SMOFlipid Infusion to Treat Severe Asparaginase-Induced Hypertriglyceridemia in Two Pediatric Acute Lymphoblastic Leukemia Patients

2021 ◽  
Vol 9 ◽  
Author(s):  
Sie Chong Doris Lau ◽  
C-Khai Loh ◽  
Hamidah Alias
Keyword(s):  
Case Report ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Treatment Phase ◽  
Concurrent Infection ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Hyperviscosity Syndrome ◽  
Clinical Presentations ◽  
Life Threatening

Asparaginase-induced hypertriglyceridemia can have a spectrum of clinical presentations, from being asymptomatic to having life-threatening thrombosis or hyperviscosity syndrome. At present, there is no recommendation on routine lipid monitoring during asparaginase-containing treatment phase, nor a standardized guideline on its management. Two cases are presented here to illustrate the effects of concurrent infection on asparaginase-induced hypertriglyceridemia in patients with high-risk ALL and the use of SMOFlipid infusion as a treatment option in an acute situation.

Life-Threatening Hypercalcemia Complicated by Pancreatitis in a Child With Acute Lymphoblastic Leukemia

2005 ◽  
Vol 27 (5) ◽  
pp. 288-292 ◽  
Author(s):  
Elpis Mantadakis ◽  
Nicole Anagnostatou ◽  
Penelope Smyrnaki ◽  
Anna-Maria Spanaki ◽  
Efstathios S Papavasiliou ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Life Threatening

Inosine-Triphosphate-Pyrophosphatase Genotype Is a Determinant of Severe Fever with Neutropenia Following Treatment of Acute Lymphoblastic Leukemia with Combination Chemotherapy That Includes Mercaptopurine Adjusted for Thiopurine-S-Methyltransferase Genotype.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2827-2827
Author(s):  
Gabriele Stocco ◽  
Meyling Cheok ◽  
Wenjian Yang ◽  
Thierry Dervieux ◽  
Kristine Crews ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Acute Lymphoblastic Leukemia ◽  
Adverse Events ◽  
Lymphoblastic Leukemia ◽  
Variant Allele ◽  
Inosine Triphosphate Pyrophosphatase ◽  
Life Threatening ◽  
Variant Alleles ◽  
Grade 3 ◽  
Tpmt Gene

Abstract Germline polymorphisms can be significant determinants of toxicity to anti-leukemic therapy. For mercaptopurine (6MP) it is established that variant alleles of the thiopurine-S-methyl-transferase (TPMT) gene, resulting in low enzymatic activity, are associated with an increase in the concentration of thioguanine-nucleotide metabolites (TGN) and in the risk of hematotoxicity. Polymorphisms of genes encoding other enzymes involved in 6MP metabolism could also influence its pharmacokinetics and consequently its efficacy and toxicity. Among possible candidate genes, inosine-triphosphate-pyrophosphatase (ITPA) has been related to adverse events to thiopurine treatment of inflammatory bowel disease, but it has not been fully investigated for leukemia therapy. The aim of this study was to assess the association between severe life-threatening toxicities (Grade 3–4) during the continuation treatment of acute lymphoblastic leukemia (ALL) and the variant alleles of TPMT and ITPA genes, and the influence of these variant alleles on the concentration of 6MP metabolites, TGN and methylated nucleotides (MMPN). Patients with ALL on the St. Jude Total 13B protocol were assessed for toxicity according to NCI criteria. Relevant variant alleles of TPMT (SNPs rs1142345, rs1800462, rs1800660) and ITPA (SNP rs41320251) were determined using PCR assays. The association between the variant alleles and the development of adverse events during the continuation phase of treatment was assessed using weighted logistic regression. Concentrations of the two main metabolites of 6MP were measured in erythrocytes by HPLC; the association between genotypes and the concentrations of 6MP metabolites was evaluated using mixed linear effects models. TPMT and ITPA genotypes were determined for 233 patients; 13 (5.2%) were heterozygous for variant alleles of the TPMT gene and 31 (13.3%) for the ITPA gene; no patient had two variant alleles of either gene and 1 patient (0.4%) had a variant allele for both TPMT and ITPA. Since 6MP dose was individualized based on the TPMT variant allele among patients treated in the protocol, genetic polymorphisms of TPMT, not surprisingly, were not associated with toxicity. On the other hand, the presence of an ITPA variant allele was significantly associated with the incidence of Grade 3–4 fever with neutropenia in the univariate and in the multiple weighted logistic regression (odds ratio 3.0, 95% C.I. 1.2–7.8, p = 0.021). 6MP metabolites were measured in 257 samples from 108 patients, and the results revealed that variant alleles of both candidate genes were associated with changes in the concentration of the MMPN metabolites: TPMT with a reduction (p = 0.048) and ITPA with an increase (p = 0.047). Genetic polymorphism of ITPA rs41230251 is a significant determinant of severe and life-threatening fever with neutropenia and of 6MP metabolism in patients with ALL who are treated with 6MP doses individualized based on TPMT genotype.

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