Haematologica 2002; 87:(02)ELT05
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Lactic acidosis in Non-Hodgkin's lymphoma and response to chemotherapy.
Santiago Osorio*, Carmen Bernis #, Rafael de la Cámara*
Departments of *Haematology and #Nephrology, Hospital de la Princesa, C/Diego de León Nº 62, Madrid 28006, Spain

Correspondence: Dr. Rafael de la Cámara, Department of Haematology, de la Princesa, C/Diego de León Nº 62, Madrid 28006, Spain. Fax: +34-91-5202326. e-mail: r.camara@retemail.es
Lactic acidosis without clinically evident tissue hypoxia is a metabolic disorder rarely seen in patients with malignancies such as solid tumors, acute leukemias, and lymphomas. Although the association between lymphoma and lactic acidosis was described in 1964,1 well-documented cases are very rare. We report a case with an atypical high-grade non-Hodgkin´s lymphoma (NHL) with extensive liver involvement (without hepatomegaly and normal liver signal on the computed tomography) without lymphadenopathy, an isolated colonic lesion, who developed a severe lactic acidosis resolved with chemotherapy.
Case report. A 70 year-old man was admitted to the Haematology Department with a diagnosis of NHL of the colon with liver metastases. His past medical history included an adenocarcinoma of the colon (stage B2) 8 years before, treated successfully with chemotherapy. In a routine outpatient revision, liver function tests showed mild alteration and an abdominal ultrasound disclosed two nodular lesions in the right hepatic lobe. Metastases of a relapsed colonic adenocarcinoma were suspected and a colonoscopy was performed finding only an ulcerated lesion. The biopsy of the ulcer disclosed a diffuse large B-cell lymphoma and the patient was transferred to the Haematology Department. Physical examination on admission revealed: an afebrile patient with tachypnea (respiratory rate of 36 per min), normal oxygen saturation (98%), blood pressure of 120/80 mm Hg, no signs of circulatory failure, mild disorientation, asterixis, moderate edema in both legs, and no lymphadenopathy or hepatosplenomegaly. Laboratory data revealed a hemoglobin of 10.3 g/dL, leukocytes 13,150/mm3, platelets 94,000/mm3, urea 128 mg/dL, creatinine 1.3 mg/dL, glucose 246 mg/dL, total bilirrubin 1.4 mg/dL, GGT 180 U/L (normal, 7-32), alkaline phosphatase 294 U/L (normal, 91-258), LDH 584 U/L (normal, 240-480), albumin 1.8 gr/dL, proteinuria 416 mg/24h (normal 0-150 mg), sodium 133 meq/L, potassium 7.3 meq/L, chloride 98 meq/L, and urine pH of 5. Coagulation tests, GOT, GPT and ammonium were normal. Venous blood gas determination showed a pH of 7.25, a PCO2 of 19-mm Hg and bicarbonate 8.3 meq/l. The anion gap was 34 (normal, 12-15). The serum lactate was 94 mg/dL (normal<15 mg/dL). Computed tomographic scan of the abdomen, chest and neck disclosed a normal liver (in size and density) without focal lesions; no lymphadenopathy at any level; and a moderate increase in size of both adrenal glands with normal morphology suggestive of adrenal hyperplasia. A liver biopsy performed six days after admission confirmed the diagnosis of diffuse infiltration by a high grade NHL. The bone marrow biopsy also showed infiltration by NHL. Initial treatment included an intravenous infusion of high doses of sodium bicarbonate, which normalized blood pH but not the serum lactate that continued raising, reaching a maximum level of 217 mg/dL after nine days of treatment. On the 9th day of hospitalization, chemotherapy was initiated with the first week of VACOP-Bleo regimen. After two days the sodium bicarbonate infusion was stopped and 2 days later the serum lactate level normalized (12 mg/dL). Unfortunately the patient developed several complications including pneumonia, fluid retention with pulmonary edema and died on the 16th day in hospital.
Comment. The mechanism of lactic acidosis associated with lymphoma remains obscure. Most of the published cases had hepatic tumor involvement, suggesting that both enhanced lactate formation by the tumor and decreased lactate metabolism by the liver play a role.2 This combination of factors would explain why these patients develop lactic acidosis with mild alterations in liver function tests whilst patients with severe liver failure of other etiologies do not. However it is still unknown why some patients with lymphoma develop this disorder, considering that the majority of the patients even with liver involvement and more extensive diseases never have this acid-base disturbance. The response of the acidosis to chemotherapy has been rapid and complete in several cases,3-8 as in our case. Sodium bicarbonate can compensate for the acidosis, but it is not effective in reverting lactate serum level, and it is not without hazards since lethal hyperosmolality and volume overload have been observed.2 The treatment of choice is chemotherapy. The cytoreduction achieved by this treatment and a better lactate clearance due to improved liver function are the best explanations of its effectiveness. Lactic acidosis is a bad prognostic factor in patients with lymphoma, associated with a high short-term mortality.4-6,9 Consequently this situation should be considered to constitute an oncology emergency, and chemotherapy should be started as soon as possible. Some complete remissions have been described3,5 and the prompt administration of therapy was considered an important factor in these cases.

 

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