Contributions
Abstract: PB1609
Type: Publication Only
Session title: Lymphoma Biology & Translational Research
Background
A malignancy-induced lactic acidosis is a rare event that is largely associated with hematologic malignancies (leukemias and lymphomas). It is a subset of type B lactic acidosis that is mediated without evidence of tissue hypoperfusion, pathophysiology that is centered around the Warburg effect and is associated with poor outcomes. Thiamine pyrophosphate is a vital cofactor for pyruvate dehydrogenase, which irreversibly converts pyruvate to acetyl-CoA, committing the pathway in a way that it cannot be reversed back to anaerobic respiration. We hypothesize in the presence of a high level of cofactors responsible for this step, the glycolysis pathway might be skewed to an otherwise anaerobic preference.
Aims
To evaluate if high dose thiamine can reverse malignancy-induced lactic acidosis in patients with hematological malignancies.
Methods
Retrospective-single center review of malignancy-induced lactic acidosis that has been treated empirically with high dose thiamine between 2015 and 2020. Patients with not enough data on the lactic acid level, or an alternative explanation for the lactic acidosis is present, were excluded.
Results
Case 1: 19-year-old male with a history of Classical Hodgkin's Lymphoma 3 years before his presentation with symptoms of fatigue and shortness of breath. His CBC revealed pancytopenia with ANC 0.3 x109/L and platelets of 9 x 109/L. Metabolic acidosis was noted on presentation with bicarbonate 9.5 mmol/L and lactic acid of 13.23 mmol/L. PET scan showed above and below diagram lymphadenopathy with cutaneous and subcutaneous and bone marrow activity. He was given thiamine 100 mg IV TID for 7 days pending the establishment of diagnosis by biopsy. Lactate normalized during this time, with only cofounding agent been steroids. The final diagnosis was T-cell lymphoma with Ki67 of more than 90% with bone marrow showing evidence of hemophagocytic lymphohistiocytosis [Figure].
Case 2: 15-year-old female with no past medical history who presented with gum bleeding and abdominal pain for 7 days. CBC revealed WBC of 10 x109/L and platelets of 12 x109/L. Biochemistry showed metabolic acidosis with bicarbonate of 11 mmol/L and lactic acid of 5.4 mmol/L. LDH was more than the upper limit of detection (>2000). The patient was started on thiamine 100 mg TID for 2 days with normalization of lactate in 36 hours. Bone marrow biopsy was difficult to aspirate and biopsy showed 100% cellularity with 70% blast. Diagnosis of Philadelphia negative B-ALL was made, and the patient was treated on pediatric ALL protocol [Figure].
Case 3: 22-year-old male with no past medical history presented with epistaxis, shortness of breath, scrotal and generalized edema. He had hepatosplenomegaly on the exam with a tender spleen. Imagining revealed renal hypodensities with ascites and bilateral pleural effusion. CBC showed WBC of 16 x109/L and platelets of 8 x109/L. Biochemistry showed LDH of 1123 U/L with a picture of metabolic acidosis. Bicarbonate was 16 mmol/L and lactic acid was 8.6-12.8 mmol/L for four days before starting on thiamine 100 mg IV TID with normalization of lactate in 3 days. The patient's bone marrow showed 100% cellularity with 75% blast. The diagnosis of Philadelphia negative B-ALL was made, and the patient was started on pediatric-inspired protocol [Figure].
Conclusion
Malignancy-induced lactic acidosis related to the Warburg effect or thiamine pyrophosphate deficiency at a cellular level, high dose thiamine, and/or other cofactors like riboflavin, might be useful in treating this disorder, meriting further investigation.
Keyword(s): Acute lymphoblastic leukemia, Lymphoma, Peripheral T-cell lymphoma, Tumorigenesis
Abstract: PB1609
Type: Publication Only
Session title: Lymphoma Biology & Translational Research
Background
A malignancy-induced lactic acidosis is a rare event that is largely associated with hematologic malignancies (leukemias and lymphomas). It is a subset of type B lactic acidosis that is mediated without evidence of tissue hypoperfusion, pathophysiology that is centered around the Warburg effect and is associated with poor outcomes. Thiamine pyrophosphate is a vital cofactor for pyruvate dehydrogenase, which irreversibly converts pyruvate to acetyl-CoA, committing the pathway in a way that it cannot be reversed back to anaerobic respiration. We hypothesize in the presence of a high level of cofactors responsible for this step, the glycolysis pathway might be skewed to an otherwise anaerobic preference.
Aims
To evaluate if high dose thiamine can reverse malignancy-induced lactic acidosis in patients with hematological malignancies.
Methods
Retrospective-single center review of malignancy-induced lactic acidosis that has been treated empirically with high dose thiamine between 2015 and 2020. Patients with not enough data on the lactic acid level, or an alternative explanation for the lactic acidosis is present, were excluded.
Results
Case 1: 19-year-old male with a history of Classical Hodgkin's Lymphoma 3 years before his presentation with symptoms of fatigue and shortness of breath. His CBC revealed pancytopenia with ANC 0.3 x109/L and platelets of 9 x 109/L. Metabolic acidosis was noted on presentation with bicarbonate 9.5 mmol/L and lactic acid of 13.23 mmol/L. PET scan showed above and below diagram lymphadenopathy with cutaneous and subcutaneous and bone marrow activity. He was given thiamine 100 mg IV TID for 7 days pending the establishment of diagnosis by biopsy. Lactate normalized during this time, with only cofounding agent been steroids. The final diagnosis was T-cell lymphoma with Ki67 of more than 90% with bone marrow showing evidence of hemophagocytic lymphohistiocytosis [Figure].
Case 2: 15-year-old female with no past medical history who presented with gum bleeding and abdominal pain for 7 days. CBC revealed WBC of 10 x109/L and platelets of 12 x109/L. Biochemistry showed metabolic acidosis with bicarbonate of 11 mmol/L and lactic acid of 5.4 mmol/L. LDH was more than the upper limit of detection (>2000). The patient was started on thiamine 100 mg TID for 2 days with normalization of lactate in 36 hours. Bone marrow biopsy was difficult to aspirate and biopsy showed 100% cellularity with 70% blast. Diagnosis of Philadelphia negative B-ALL was made, and the patient was treated on pediatric ALL protocol [Figure].
Case 3: 22-year-old male with no past medical history presented with epistaxis, shortness of breath, scrotal and generalized edema. He had hepatosplenomegaly on the exam with a tender spleen. Imagining revealed renal hypodensities with ascites and bilateral pleural effusion. CBC showed WBC of 16 x109/L and platelets of 8 x109/L. Biochemistry showed LDH of 1123 U/L with a picture of metabolic acidosis. Bicarbonate was 16 mmol/L and lactic acid was 8.6-12.8 mmol/L for four days before starting on thiamine 100 mg IV TID with normalization of lactate in 3 days. The patient's bone marrow showed 100% cellularity with 75% blast. The diagnosis of Philadelphia negative B-ALL was made, and the patient was started on pediatric-inspired protocol [Figure].
Conclusion
Malignancy-induced lactic acidosis related to the Warburg effect or thiamine pyrophosphate deficiency at a cellular level, high dose thiamine, and/or other cofactors like riboflavin, might be useful in treating this disorder, meriting further investigation.
Keyword(s): Acute lymphoblastic leukemia, Lymphoma, Peripheral T-cell lymphoma, Tumorigenesis