Warburg effect mimicking inborn errors of metabolism in childhood hematologic malignancies: A case-based systematic review

Table 1 Inclusion and exclusion criteria

Criteria
Inclusion
Children, 0 to 18 yr
Diagnosis of hematologic malignancy, including leukemia and lymphoma
Presence of lactic acidosis
Availability of clinical course, treatment, and outcome data
Exclusion
Adults, > 18 yr
Diagnosis of other solid tumors
Presence of other causes of metabolic acidosis without lactic acidosis
Incomplete information regarding clinical courses, treatment, and outcomes

Table 2 Demographics, treatments, and outcomes of previously reported children with leukemia/lymphoma and type B lactic acidosis

Ref.	Primary diagnosis	Age in yr, Sex	Clinical manifestation	Initial lactate in mmol/L	Blood glucose in mg/dL	Hepatic involvement	Renal involvement	Treatment	Clinical course
									Lactic acidosis	Outcome
Type B lactic acidosis-Warburg effect
Field et al[8]	Relapsed ALL	4, M	Bleeding, hepatosplenomegaly	20.2	NR	Yes	NR	Bicarbonate, radiotherapy, chemotherapy	Improved but recurred	Death from disease
	ALL	8, M	NR	9.9	NR	NR	NR	Bicarbonate, chemotherapy	Improved but recurred	Death from infection
Coleman et al[9]	Relapsed T-ALL	2, M	Lymphadenopathy, splenomegaly, dyspnea	24.6	74	No	NR	Bicarbonate, thiamine, insulin, methylglyoxal	Improved but recurred	Death from disease
Ali et al[10]	Relapsed B-ALL	12, M	Poor appetite, weight loss, abdominal pain	12.0	NR	No	Yes	Bicarbonate, chemotherapy	Improved but recurred	Death from infection
Révész et al[11]	Relapsed Burkitt lymphoma	8, M	Seizure, altered mental status, dyspnea, polydipsia, polyuria	24.0	93	No	Yes	Bicarbonate, thiamine, chemotherapy, radiotherapy	Improved but recurred	Death from disease
Sillos et al[3]	Relapsed T-ALL	11, F	Altered mental status	10.8	47	Yes	No	Bicarbonate, CRRT, chemotherapy	Improved but recurred	Death from disease
	Relapsed T-ALL	17, M	Altered mental status, dyspnea, edema	16.0	132	No	No	Bicarbonate	Worsened	Death from disease
	T-NHL	18, F	Fever, weight loss, lymphadenopathy, splenomegaly, dyspnea	15.4	44	Yes	No	Bicarbonate, chemotherapy	Resolved but recurred	Death from disease
Hayek and Srinivasan[12]	B-ALL	7, M	Anemia, lymphadenopathy, hepatosplenomegaly	8.4	96	Yes	Yes	Bicarbonate, PD, chemotherapy	Resolved after chemotherapy	CR
Rastogi et al[13]	Burkitt lymphoma, HIV	11, M	Fever, hepatosplenomegaly, periorbital and pedal edema	4.2	26	Yes	NR	Bicarbonate, glucagon	Improved	Death from disease
Luscri et al[14]	Relapsed B-ALL	7, M	Fever, ascites, dyspnea	5.5	33	Yes	NR	Bicarbonate, CRRT	Worsened	Death from LA, disease
Kulkarni et al[15]	Burkitt lymphoma	12, M	Dyspnea, hepatomegaly, abdominal pain	21.0	Normal	Yes	Yes	Bicarbonate, chemotherapy	Resolved after chemotherapy	CR
Terpe et al[16]	B-ALL	11, M	Nausea, dyspnea, lymphadenopathy, abdominal pain, pancytopenia	21.0	48	Yes	Yes	Bicarbonate, chemotherapy	Worsened	Death from LA, ACS
Gökçe et al[17]	B-ALL	13, M	Weight loss, nausea, bone pain	62.0	97	Yes	Yes	Bicarbonate, chemotherapy	Resolved after chemotherapy	CR
Schuh et al[18]	Relapsed B-ALL	12, M	Fever, abdominal pain, bicytopenia	14.8	80	Yes	Yes	Chemotherapy	Worsened	Death from disease
Narayani et al[19]	ALL	2, M	Fever, pancytopenia	13.5	96	NR	No	Bicarbonate, chemotherapy	Resolved after chemotherapy	CR
Khera et al[20]	T-ALL	11, F	Poor appetite, weight loss, nausea, dyspnea, bicytopenia	20.0	104	No	No	Bicarbonate, chemotherapy	Resolved after chemotherapy	CR
O'Rourke et al[21]	Burkitt leukemia	13, M	NR	NR	Low	NR	NR	Chemotherapy	Worsened	Death from LA
Hui et al[22]	Relapsed B-ALL	17, F	Poor appetite, weight loss, bicytopenia	15.0	NR	NR	No	Bicarbonate CRRT	Improved	NR
This study	Burkitt leukemia	10, M	Poor appetite, nausea, vomiting	3.7	49	No	Yes	Rituximab, chemotherapy	Resolved after chemotherapy	CR
Type B lactic acidosis-thiamine deficiency
Oriot et al[23]	Relapsed ALL, on TPN without vitamin	3, M	Altered mental status, fever, dyspnea, hepatomegaly	30.0	43	Yes	No	Bicarbonate, PD, thiamine	Resolved	CR
Svahn et al[24]	B-ALL, on TPN without vitamin	0.9, F	Altered mental status	18.6	NR	NR	NR	Bicarbonate, multivitamin including thiamine	Resolved	CR
Didisheim et al[25]	ALL, post-sepsis	13, M	Fever, abdominal pain, hypotension	19.6	NR	NR	NR	ECMO, thiamine	Resolved	CR
Type B lactic acidosis-medication (s)
Smolka et al[26]	Relapsed B-ALL, pneumonia (antibiotics including linezolid)	9, F	Altered mental status, dyspnea	19.0	NR	Yes	NR	Bicarbonate, withdraw linezolid	Improved	CR

ACS: Abdominal compartment syndrome; ALL: Acute lymphoblastic leukemia; CR: Complete response; CRRT: Continuous renal replacement therapy; ECMO: Extracorporeal membrane oxygenation; F: Female; LA: Lactic acidosis; M: Male; NR: Not reported; PD: Peritoneal dialysis.