- Email: [email protected]
A Case of Type B Lactic Acidosis in Multiple Myeloma
Case Report
A Case of Type B Lactic Acidosis in Multiple Myeloma Patrick Tang,1 Anamarija M. Perry,2 Mojtaba Akhtari1 Clinical Practice Points ●
●
●
Type A lactic acidosis occurs secondary to tissue hypoxia and anaerobic metabolism, whereas type B lactic acidosis is a rare condition related to underlying diseases, errors in metabolism, medications, or intoxication. Type B lactic acidosis is rare in patients with malignancies, and review of published cases shows that most cases of type B lactic acidosis were associated with hematologic malignancies, predominantly lymphomas. There have only been 2 reported cases of type B lactic acidosis-associated multiple myeloma.
●
● ●
●
We present a patient with multiple myeloma and marked lactic acidosis without evidence of infection or organ hypoperfusion. The mechanism of lactic acidosis in malignancy is unknown; however, several hypotheses have been proposed. Management options for type B lactic acidosis might include chemotherapy, renal replacement therapy, bicarbonate supplementation, and thiamine supplementation. Physicians should be aware of advanced and recurring malignancy as a cause of lactic acidosis and that treatment of the underlying disease should be initiated promptly.
Clinical Lymphoma, Myeloma & Leukemia, Vol. 13, No. 1, 80-2 © 2013 Elsevier Inc. All rights reserved. Keyword: Type B lactic acidosis, Multiple myeloma
Introduction
Case Report
Type B lactic acidosis is rare in patients with malignancies. We report a case of a 58-year-old man who was admitted for dyspnea, and was found to have severe lactic acidosis from relapsed multiple myeloma (MM). The degree of lactic acidosis transiently improved with chemotherapy and hemodialysis and worsened when therapies were withdrawn. We also present a brief review of literature on type B lactic acidosis occurring with MM and its proposed mechanisms. This case highlights the importance of recognizing lactic acidosis as a manifestation of an aggressively relapsing hematologic malignancy. Type A lactic acidosis occurs secondary to tissue hypoxia and anaerobic metabolism, whereas type B lactic acidosis is a rare condition related to underlying diseases, errors in metabolism, medications, or intoxication.1 Review of published cases documents that most cases of type B lactic acidosis were associated with hematological malignancies, predominantly lymphomas (Table 1).2-22 There have only been 2 reported cases of type B lactic acidosis-associated MM.18,23
A 58-year-old Caucasian man with kappa light chain MM diagnosed in 1998 received 6 cycles of VAD (vincristine, adriamycin, and dexamethasone) followed by autologous hematopoietic stem cell transplant (HSCT) after his first complete response in October 1998. In 2008, his monoclonal protein began to rise, and bone marrow biopsy at the time showed recurrent plasma cell myeloma with myeloma cells comprising 12% of total cells. He elected to proceed with bortezomib therapy and received 4 cycles, ending in April of 2009, and experienced overwhelming peripheral neuropathy and fatigue. Thereafter, bone marrow biopsy showed 24% plasma cells. Therapy was switched to lenalidomide and dexamethasone, but the patient had a minimal response after 4 cycles. The bone marrow was markedly hypercellular with extensive involvement by plasma cell myeloma, with associated plasma cell leukemia with 21% plasma cells in the peripheral blood. He then received an additional 6 cycles of VAD, ending in late 2010, and achieved a partial response with 4% plasma cells detected in the bone marrow by flow cytometry. Because he had a long remission with his first HSCT, he underwent a second autologous HSCT in April of 2011. Unfortunately, in July 2011 he had evidence of residual disease on day 100 posttransplant with detectable free kappa light chains in the urine. In an outpatient follow-up in August 2011, he reported 3 weeks of progressive shortness of breath and malaise. He was sent to the emergency room and was found to have a lactic acid of 14.7 mmol/L (reference range, 0.5-2.2 mmol/L) and bicarbonate of 7 mmol/L (reference range,
1 Division of Hematology and Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Submitted: Mar 7, 2012; Revised: Jun 17, 2012; Accepted: Jul 26, 2012; Epub: Sep 24, 2012 Address for correspondence: Mojtaba Akhtari, MD, UNMC Hematology and Oncology Division, 987680 Nebraska Medical Center, Omaha, NE 68198-7680 Fax: 402-559-6520; e-mail contact: [email protected]
80
Clinical Lymphoma, Myeloma & Leukemia February 2013
2152-2650/$ - see frontmatter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2012.07.005
Table 1 Summary of Case Reports of Type B Lactic Acidosis from 2000 to 2010
Hematologic Malignancies
Number of Cases
Percent of Total Cases
27
87
References
Lymphomas
18
58
NHL
17
55
13-15
HL
1
3
23
8
26
ALL
5
16
6,15-17
AML
2
6
5,22
Leukemias
CLL
1
3
5
MM
1
3
18
4
13
14,19-21
Solid Malignancies
Figure 1 Peripheral Blood Smear Showing Atypical Plasma Cells (arrows). Inset: Plasma Cells are Large, With Prominent Nucleoli and Vacuolated Cytoplasm (Wright-Giemsa, original magnification ⴛ200; Inset, Wright Giemsa, oil objective, original magnification ⴛ600)
Abbreviations: ALL ⫽ acute lymphoblastic leukemia; AML ⫽ acute myeloid leukemia; CLL ⫽ chronic lymphocytic leukemia; HL ⫽ Hodgkin’s lymphoma; MM ⫽ multiple myeloma; NHL ⫽ non–Hodgkin’s lymphoma. Adapted from Ruiz et al.3
22-32 mmol/L). Despite marked lactic acidosis on presentation, the patient was not ill-appearing and was hemodynamically stable and oxygenating well. However, the acidosis became overwhelming and continuous bicarbonate infusion and mechanical ventilation was begun. He improved the day after and was extubated. Cardiac enzymes, liver function tests, and renal function were within normal limits. He was transferred to our care in a stable condition 4 days thereafter in consideration for chemotherapy because his peripheral smear showed 11% circulating plasma cells. Although he was clinically improved and hemodynamically stable, lactic acid was markedly elevated at 21.5 mmol/L with serum bicarbonate of 13 mmol/L. Before starting therapy, a bone marrow biopsy was performed and showed a hypercellular bone marrow (85%) with extensive involvement by plasma cell myeloma, with associated 22% circulating plasma cells in the peripheral blood (Figures 1 and 2). He then received a regimen of bortezomib, lenalidomide, and dexamethasone followed by VRD-PACE (cisplatin, doxorubicin, cyclophosphamide, and etoposide).24 On day 3 of chemotherapy, his acidosis worsened and peripheral plasma cells increased to 66% as he again had respiratory failure requiring mechanical ventilation. His lactic acid was 16.5 mmol/L with worsening acidosis from bicarbonate of 9 mmol/L. Hemodialysis was initiated for severe acidosis and empiric antibiotics were given although no source of infection was identified. Eventually, the diagnosis of diffuse alveolar hemorrhage was made on bronchoscopy. Over the next week, his lactic acid decreased and acidosis improved with continued chemotherapy and dialysis, and he was extubated. With understanding of his clinical situation, he requested comfort measures only, and subsequently expired from respiratory failure soon after hemodialysis was withdrawn. An autopsy was not performed because the patient had decided to participate in organ donation.
Figure 2 Bone Marrow Aspirate Showing Extensive Involvement by Plasma Cell Myeloma (53% plasma cells by differential count). Clusters of Markedly Atypical, Enlarged Plasma Cells With Irregular Nuclei, Conspicuous Nucleoli, and Cytoplasmic Vacuoles (Wright-Giemsa, oil objective, original magnification ⴛ600)
Discussion Our patient had marked lactic acidosis without evidence of infection or organ hypoperfusion. It is very likely that his acidosis was secondary to relapsed myeloma. This is the third documented case of type B lactic acidosis in a patient with MM. Common features to previously described cases are rapidly progressive disease with presentation of hemodynamically stable marked lactic acidosis. Our patient’s death was secondary to overwhelming disease burden and lactic acid production leading to respiratory failure.
Clinical Lymphoma, Myeloma & Leukemia February 2013
81
Type B Lactic Acidosis in Multiple Myeloma Typically, type B lactic acidosis occurs in patients with acute rapidly progressive hematological malignancies such as leukemia or lymphoma.2 The mechanism of lactic acidosis in malignancy is unknown; however, several hypotheses have been proposed. In addition to overproduction of lactic acid from large tumor burden and rapid cell turnover, tumor cells may not obtain an adequate oxygen supply and switch to anaerobic glycolysis to satisfy energy requirements.25 This abnormal metabolic change may enable tumor cells to acquire and metabolize nutrients in a way that favors proliferation over efficient adenosine triphosphate production.26 A possible biochemical explanation includes defective lactic acid metabolism from presence of tumor necrosis factor ␣ or thiamine deficiency which reduces activity of pyruvate dehydrogenase that converts pyruvate to acetyl-coA.5,27 Other proposed mechanisms leading to worsening lactic acidosis involve tumor microembolism, and decreased degradation of lactic acid because of liver involvement.28 Management options for type B lactic acidosis may include chemotherapy, renal replacement therapy, bicarbonate supplementation, and thiamine supplementation. Because of the lack of randomized trials evaluating each of the above modalities, it is difficult to determine which therapies have any therapeutic effect. Based on observation of the available literature to date, it seems as though the majority of patients who develop type B lactic acidosis secondary to malignancy have a poor outcome, and thus, this complication might serve as an indicator of a poor prognosis. Physicians should be aware of advanced and recurring malignancy as a cause of lactic acidosis and that treatment of the underlying disease should be initiated promptly.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Vernon C, Letourneau JL. Lactic acidosis: recognition, kinetics, and associated prognosis. Crit Care Clin 2010; 26:255-83, table of contents, 83. 2. Block JB. Lactic acidosis in malignancy and observations on its possible pathogenesis. Ann N Y Acad Sci 1974; 230:94-102. 3. Ruiz JP, Singh AK, Hart P. Type B lactic acidosis secondary to malignancy: case report, review of published cases, insights into pathogenesis, and prospects for therapy. ScientificWorldJournal 2011; 11:1316-24. 4. de Groot R, Sprenger RA, Imholz AL, et al. Type B lactic acidosis in solid malignancies. Neth J Med 2011; 69:120-3.
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Clinical Lymphoma, Myeloma & Leukemia February 2013
5. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: A case series from a single institution and literature review. Medicine (Baltimore) 2007; 86:225-32. 6. Sillos EM, Shenep JL, Burghen GA, et al. Lactic acidosis: a metabolic complication of hematologic malignancies: case report and review of the literature. Cancer 2001; 92:2237-46. 7. Prikis M, Bhasin V, Young MP, et al. Sustained low-efficiency dialysis as a treatment modality in a patient with lymphoma-associated lactic acidosis. Nephrol Dial Transplant 2007; 22:2383-5. 8. Diab K, Knox KS, Hage CA. An 81-year-old man with lactic acidosis, refractory hypoglycemia, and lymphocytosis. Chest 2008; 133:306-10. 9. Svahn J, Schiaffino MC, Caruso U, et al. Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy. J Pediatr Hematol Oncol 2003; 25:965-8. 10. Di Comite G, Dagna L, Piatti PM, et al. Hypoglycaemia and lactic acidosis in a MALT non Hodgkin’s lymphoma. Leuk Lymphoma 2002; 43:1341-2. 11. He YF, Wei W, Sun ZM, et al. Fatal lactic acidosis and hypoglycemia in a patient with relapsed natural killer/T-cell lymphoma. Adv Ther 2007; 24:505-9. 12. Ohtsubo K, Imamura R, Seki R, et al. Blastoid variant of mantle cell lymphoma with lactic acidosis: A case report. Int J Hematol 2004; 80:428-31. 13. Mosunjac MB, Sundstrom JB, Mosunjac MI. Unusual presentation of anaplastic large cell lymphoma with clinical course mimicking fever of unknown origin and sepsis: autopsy study of five cases. Croat Med J 2008; 49:660-8. 14. Manuel B, Suresh V, Saphwat E. Refractory metabolic acidosis in small cell cancer of the lung. South Med J 2006; 99:782-3. 15. De Keulenaer B, Van Outryve S, De Backer A, et al. Symptomatic lactic acidosis due to relapse of T-cell acute lymphoblastic leukaemia in the kidney. Nephrol Dial Transplant 2003; 18:1214-6. 16. Hayek M, Srinivasan A. Acute lymphoblastic leukemia presenting with lactic acidosis and renal tubular dysfunction. J Pediatr Hematol Oncol 2003; 25:488-90. 17. Luscri N, Mauer M, Sarafoglou K, et al. Lactic acidosis and hypoglycemia with ALL relapse following engrafted bone marrow transplant. Pediatr Blood Cancer 2009; 53:223-5. 18. Ustun C, Fall P, Szerlip HM, et al. Multiple myeloma associated with lactic acidosis. Leuk Lymphoma 2002; 43:2395-7. 19. Cheng JC, Esparza SD, Knez VM, et al. Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated carcinoma of unknown primary. J Pediatr Hematol Oncol 2004; 26:780-2. 20. Chau WK, Yang CF, Chou YH, et al. Aggressive undifferentiated carcinoma of unknown primary site complicated by lactic acidosis after bleeding: A case report. Jpn J Clin Oncol 2002; 32:210-4. 21. Wall BM, Mansour N, Cooke CR. Acute fulminant lactic acidosis complicating metastatic cholangiocarcinoma. Am J Med Sci 2000; 319:126-9. 22. Dogan E, Erkoc R, Sayarlioglu H, et al. Fatal lactic acidosis due to leukemic transformation in a patient with non-Hodgkin’s lymphoma: case report. Adv Ther 2005; 22:443-6. 23. Mizock BA, Glass JN. Lactic acidosis in a patient with multiple myeloma. West J Med 1994; 161:417-8. 24. Barlogie B, Anaissie EJ, Shaughnessy JD, Jr., et al. Ninety percent sustained complete response (CR) rate projected 4 years after onset of CR in gene expression profiling (GEP)-defined low-risk multiple myeloma (MM) treated with total therapy 3 (TT3): basis for GEP-risk-adapted TT4 and TT5 [Abstract]. ASH Annual Meeting Abstracts 2008; 112:162. 25. Madias NE. Lactic acidosis. Kidney Int 1986; 29:752-74. 26. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324:1029-33. 27. Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001; 12(Suppl 17):S15-9. 28. Lee HS, Kim HJ, Choi S, et al. A case of type B lactic acidosis in acute leukemia. Yonsei Med J 2010; 51:460-2.
A Case of Type B Lactic Acidosis in Multiple Myeloma Patrick Tang,1 Anamarija M. Perry,2 Mojtaba Akhtari1 Clinical Practice Points ●
●
●
Type A lactic acidosis occurs secondary to tissue hypoxia and anaerobic metabolism, whereas type B lactic acidosis is a rare condition related to underlying diseases, errors in metabolism, medications, or intoxication. Type B lactic acidosis is rare in patients with malignancies, and review of published cases shows that most cases of type B lactic acidosis were associated with hematologic malignancies, predominantly lymphomas. There have only been 2 reported cases of type B lactic acidosis-associated multiple myeloma.
●
● ●
●
We present a patient with multiple myeloma and marked lactic acidosis without evidence of infection or organ hypoperfusion. The mechanism of lactic acidosis in malignancy is unknown; however, several hypotheses have been proposed. Management options for type B lactic acidosis might include chemotherapy, renal replacement therapy, bicarbonate supplementation, and thiamine supplementation. Physicians should be aware of advanced and recurring malignancy as a cause of lactic acidosis and that treatment of the underlying disease should be initiated promptly.
Clinical Lymphoma, Myeloma & Leukemia, Vol. 13, No. 1, 80-2 © 2013 Elsevier Inc. All rights reserved. Keyword: Type B lactic acidosis, Multiple myeloma
Introduction
Case Report
Type B lactic acidosis is rare in patients with malignancies. We report a case of a 58-year-old man who was admitted for dyspnea, and was found to have severe lactic acidosis from relapsed multiple myeloma (MM). The degree of lactic acidosis transiently improved with chemotherapy and hemodialysis and worsened when therapies were withdrawn. We also present a brief review of literature on type B lactic acidosis occurring with MM and its proposed mechanisms. This case highlights the importance of recognizing lactic acidosis as a manifestation of an aggressively relapsing hematologic malignancy. Type A lactic acidosis occurs secondary to tissue hypoxia and anaerobic metabolism, whereas type B lactic acidosis is a rare condition related to underlying diseases, errors in metabolism, medications, or intoxication.1 Review of published cases documents that most cases of type B lactic acidosis were associated with hematological malignancies, predominantly lymphomas (Table 1).2-22 There have only been 2 reported cases of type B lactic acidosis-associated MM.18,23
A 58-year-old Caucasian man with kappa light chain MM diagnosed in 1998 received 6 cycles of VAD (vincristine, adriamycin, and dexamethasone) followed by autologous hematopoietic stem cell transplant (HSCT) after his first complete response in October 1998. In 2008, his monoclonal protein began to rise, and bone marrow biopsy at the time showed recurrent plasma cell myeloma with myeloma cells comprising 12% of total cells. He elected to proceed with bortezomib therapy and received 4 cycles, ending in April of 2009, and experienced overwhelming peripheral neuropathy and fatigue. Thereafter, bone marrow biopsy showed 24% plasma cells. Therapy was switched to lenalidomide and dexamethasone, but the patient had a minimal response after 4 cycles. The bone marrow was markedly hypercellular with extensive involvement by plasma cell myeloma, with associated plasma cell leukemia with 21% plasma cells in the peripheral blood. He then received an additional 6 cycles of VAD, ending in late 2010, and achieved a partial response with 4% plasma cells detected in the bone marrow by flow cytometry. Because he had a long remission with his first HSCT, he underwent a second autologous HSCT in April of 2011. Unfortunately, in July 2011 he had evidence of residual disease on day 100 posttransplant with detectable free kappa light chains in the urine. In an outpatient follow-up in August 2011, he reported 3 weeks of progressive shortness of breath and malaise. He was sent to the emergency room and was found to have a lactic acid of 14.7 mmol/L (reference range, 0.5-2.2 mmol/L) and bicarbonate of 7 mmol/L (reference range,
1 Division of Hematology and Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Submitted: Mar 7, 2012; Revised: Jun 17, 2012; Accepted: Jul 26, 2012; Epub: Sep 24, 2012 Address for correspondence: Mojtaba Akhtari, MD, UNMC Hematology and Oncology Division, 987680 Nebraska Medical Center, Omaha, NE 68198-7680 Fax: 402-559-6520; e-mail contact: [email protected]
80
Clinical Lymphoma, Myeloma & Leukemia February 2013
2152-2650/$ - see frontmatter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2012.07.005
Table 1 Summary of Case Reports of Type B Lactic Acidosis from 2000 to 2010
Hematologic Malignancies
Number of Cases
Percent of Total Cases
27
87
References
Lymphomas
18
58
NHL
17
55
13-15
HL
1
3
23
8
26
ALL
5
16
6,15-17
AML
2
6
5,22
Leukemias
CLL
1
3
5
MM
1
3
18
4
13
14,19-21
Solid Malignancies
Figure 1 Peripheral Blood Smear Showing Atypical Plasma Cells (arrows). Inset: Plasma Cells are Large, With Prominent Nucleoli and Vacuolated Cytoplasm (Wright-Giemsa, original magnification ⴛ200; Inset, Wright Giemsa, oil objective, original magnification ⴛ600)
Abbreviations: ALL ⫽ acute lymphoblastic leukemia; AML ⫽ acute myeloid leukemia; CLL ⫽ chronic lymphocytic leukemia; HL ⫽ Hodgkin’s lymphoma; MM ⫽ multiple myeloma; NHL ⫽ non–Hodgkin’s lymphoma. Adapted from Ruiz et al.3
22-32 mmol/L). Despite marked lactic acidosis on presentation, the patient was not ill-appearing and was hemodynamically stable and oxygenating well. However, the acidosis became overwhelming and continuous bicarbonate infusion and mechanical ventilation was begun. He improved the day after and was extubated. Cardiac enzymes, liver function tests, and renal function were within normal limits. He was transferred to our care in a stable condition 4 days thereafter in consideration for chemotherapy because his peripheral smear showed 11% circulating plasma cells. Although he was clinically improved and hemodynamically stable, lactic acid was markedly elevated at 21.5 mmol/L with serum bicarbonate of 13 mmol/L. Before starting therapy, a bone marrow biopsy was performed and showed a hypercellular bone marrow (85%) with extensive involvement by plasma cell myeloma, with associated 22% circulating plasma cells in the peripheral blood (Figures 1 and 2). He then received a regimen of bortezomib, lenalidomide, and dexamethasone followed by VRD-PACE (cisplatin, doxorubicin, cyclophosphamide, and etoposide).24 On day 3 of chemotherapy, his acidosis worsened and peripheral plasma cells increased to 66% as he again had respiratory failure requiring mechanical ventilation. His lactic acid was 16.5 mmol/L with worsening acidosis from bicarbonate of 9 mmol/L. Hemodialysis was initiated for severe acidosis and empiric antibiotics were given although no source of infection was identified. Eventually, the diagnosis of diffuse alveolar hemorrhage was made on bronchoscopy. Over the next week, his lactic acid decreased and acidosis improved with continued chemotherapy and dialysis, and he was extubated. With understanding of his clinical situation, he requested comfort measures only, and subsequently expired from respiratory failure soon after hemodialysis was withdrawn. An autopsy was not performed because the patient had decided to participate in organ donation.
Figure 2 Bone Marrow Aspirate Showing Extensive Involvement by Plasma Cell Myeloma (53% plasma cells by differential count). Clusters of Markedly Atypical, Enlarged Plasma Cells With Irregular Nuclei, Conspicuous Nucleoli, and Cytoplasmic Vacuoles (Wright-Giemsa, oil objective, original magnification ⴛ600)
Discussion Our patient had marked lactic acidosis without evidence of infection or organ hypoperfusion. It is very likely that his acidosis was secondary to relapsed myeloma. This is the third documented case of type B lactic acidosis in a patient with MM. Common features to previously described cases are rapidly progressive disease with presentation of hemodynamically stable marked lactic acidosis. Our patient’s death was secondary to overwhelming disease burden and lactic acid production leading to respiratory failure.
Clinical Lymphoma, Myeloma & Leukemia February 2013
81
Type B Lactic Acidosis in Multiple Myeloma Typically, type B lactic acidosis occurs in patients with acute rapidly progressive hematological malignancies such as leukemia or lymphoma.2 The mechanism of lactic acidosis in malignancy is unknown; however, several hypotheses have been proposed. In addition to overproduction of lactic acid from large tumor burden and rapid cell turnover, tumor cells may not obtain an adequate oxygen supply and switch to anaerobic glycolysis to satisfy energy requirements.25 This abnormal metabolic change may enable tumor cells to acquire and metabolize nutrients in a way that favors proliferation over efficient adenosine triphosphate production.26 A possible biochemical explanation includes defective lactic acid metabolism from presence of tumor necrosis factor ␣ or thiamine deficiency which reduces activity of pyruvate dehydrogenase that converts pyruvate to acetyl-coA.5,27 Other proposed mechanisms leading to worsening lactic acidosis involve tumor microembolism, and decreased degradation of lactic acid because of liver involvement.28 Management options for type B lactic acidosis may include chemotherapy, renal replacement therapy, bicarbonate supplementation, and thiamine supplementation. Because of the lack of randomized trials evaluating each of the above modalities, it is difficult to determine which therapies have any therapeutic effect. Based on observation of the available literature to date, it seems as though the majority of patients who develop type B lactic acidosis secondary to malignancy have a poor outcome, and thus, this complication might serve as an indicator of a poor prognosis. Physicians should be aware of advanced and recurring malignancy as a cause of lactic acidosis and that treatment of the underlying disease should be initiated promptly.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Vernon C, Letourneau JL. Lactic acidosis: recognition, kinetics, and associated prognosis. Crit Care Clin 2010; 26:255-83, table of contents, 83. 2. Block JB. Lactic acidosis in malignancy and observations on its possible pathogenesis. Ann N Y Acad Sci 1974; 230:94-102. 3. Ruiz JP, Singh AK, Hart P. Type B lactic acidosis secondary to malignancy: case report, review of published cases, insights into pathogenesis, and prospects for therapy. ScientificWorldJournal 2011; 11:1316-24. 4. de Groot R, Sprenger RA, Imholz AL, et al. Type B lactic acidosis in solid malignancies. Neth J Med 2011; 69:120-3.
82
Clinical Lymphoma, Myeloma & Leukemia February 2013
5. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: A case series from a single institution and literature review. Medicine (Baltimore) 2007; 86:225-32. 6. Sillos EM, Shenep JL, Burghen GA, et al. Lactic acidosis: a metabolic complication of hematologic malignancies: case report and review of the literature. Cancer 2001; 92:2237-46. 7. Prikis M, Bhasin V, Young MP, et al. Sustained low-efficiency dialysis as a treatment modality in a patient with lymphoma-associated lactic acidosis. Nephrol Dial Transplant 2007; 22:2383-5. 8. Diab K, Knox KS, Hage CA. An 81-year-old man with lactic acidosis, refractory hypoglycemia, and lymphocytosis. Chest 2008; 133:306-10. 9. Svahn J, Schiaffino MC, Caruso U, et al. Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy. J Pediatr Hematol Oncol 2003; 25:965-8. 10. Di Comite G, Dagna L, Piatti PM, et al. Hypoglycaemia and lactic acidosis in a MALT non Hodgkin’s lymphoma. Leuk Lymphoma 2002; 43:1341-2. 11. He YF, Wei W, Sun ZM, et al. Fatal lactic acidosis and hypoglycemia in a patient with relapsed natural killer/T-cell lymphoma. Adv Ther 2007; 24:505-9. 12. Ohtsubo K, Imamura R, Seki R, et al. Blastoid variant of mantle cell lymphoma with lactic acidosis: A case report. Int J Hematol 2004; 80:428-31. 13. Mosunjac MB, Sundstrom JB, Mosunjac MI. Unusual presentation of anaplastic large cell lymphoma with clinical course mimicking fever of unknown origin and sepsis: autopsy study of five cases. Croat Med J 2008; 49:660-8. 14. Manuel B, Suresh V, Saphwat E. Refractory metabolic acidosis in small cell cancer of the lung. South Med J 2006; 99:782-3. 15. De Keulenaer B, Van Outryve S, De Backer A, et al. Symptomatic lactic acidosis due to relapse of T-cell acute lymphoblastic leukaemia in the kidney. Nephrol Dial Transplant 2003; 18:1214-6. 16. Hayek M, Srinivasan A. Acute lymphoblastic leukemia presenting with lactic acidosis and renal tubular dysfunction. J Pediatr Hematol Oncol 2003; 25:488-90. 17. Luscri N, Mauer M, Sarafoglou K, et al. Lactic acidosis and hypoglycemia with ALL relapse following engrafted bone marrow transplant. Pediatr Blood Cancer 2009; 53:223-5. 18. Ustun C, Fall P, Szerlip HM, et al. Multiple myeloma associated with lactic acidosis. Leuk Lymphoma 2002; 43:2395-7. 19. Cheng JC, Esparza SD, Knez VM, et al. Severe lactic acidosis in a 14-year-old female with metastatic undifferentiated carcinoma of unknown primary. J Pediatr Hematol Oncol 2004; 26:780-2. 20. Chau WK, Yang CF, Chou YH, et al. Aggressive undifferentiated carcinoma of unknown primary site complicated by lactic acidosis after bleeding: A case report. Jpn J Clin Oncol 2002; 32:210-4. 21. Wall BM, Mansour N, Cooke CR. Acute fulminant lactic acidosis complicating metastatic cholangiocarcinoma. Am J Med Sci 2000; 319:126-9. 22. Dogan E, Erkoc R, Sayarlioglu H, et al. Fatal lactic acidosis due to leukemic transformation in a patient with non-Hodgkin’s lymphoma: case report. Adv Ther 2005; 22:443-6. 23. Mizock BA, Glass JN. Lactic acidosis in a patient with multiple myeloma. West J Med 1994; 161:417-8. 24. Barlogie B, Anaissie EJ, Shaughnessy JD, Jr., et al. Ninety percent sustained complete response (CR) rate projected 4 years after onset of CR in gene expression profiling (GEP)-defined low-risk multiple myeloma (MM) treated with total therapy 3 (TT3): basis for GEP-risk-adapted TT4 and TT5 [Abstract]. ASH Annual Meeting Abstracts 2008; 112:162. 25. Madias NE. Lactic acidosis. Kidney Int 1986; 29:752-74. 26. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324:1029-33. 27. Luft FC. Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001; 12(Suppl 17):S15-9. 28. Lee HS, Kim HJ, Choi S, et al. A case of type B lactic acidosis in acute leukemia. Yonsei Med J 2010; 51:460-2.