Acute tumor lysis syndrome in large B-cell non-Hodgkin lymphoma induced by steroids and anti-CD 20.

Acute tumor lysis syndrome (ATLS) is a catastrophic complication that usually follows chemotherapy treatment of myelo-lymphoproliferative diseases. It results from massive tumor cell destruction that occurs secondary to chemotherapy and it manifests few hours to few days after initiation of treatment. It is characterized by hyperkalemia, hyperuricemia, hyperphosphatemia, hypocalcemia, lactic acidosis and acute renal failure. ATLS has been rarely encountered as a complication of steroids and monoclonal antibodies (Anti CD-20, rituximab, mabthera) in patients with non-hodgkin lymphoma (NHL). A literature review was conducted and we found three cases of steroidinduced and only one case of rituximab-induced ATLS. Among the five cases presented in Table 1 (including our case), one passed away within hours of diagnosis. A 67-year-old woman had a diagnosis of CD-20 positive large B-cell NHL in October 2002. She presented with generalized fatigue, profuse night sweating and abdominal pain of 1 month duration. Physical examination showed a right cervical lymph node of 2.5 2 cm at the posterior aspect of the sternocleidomastoid muscle. Laboratory studies showed WBC of 26.1 10/l, with 59% neutrophils, 19% lymphocytes and early myeloid elements (promyelocytes, myelocytes and metamyelocytes), hemoglobin 10.9 g/dl, platelets 183 10/l, uric acid 0.21mmol/L, BUN 10.7mmol/l, creatinine 141.4 mmol/L, serum potassium 4.9mmol/l, magnesium 1mmol/l, calcium 2.35mmol/l, phosphorus 1.22mmol/l, lactate dehydrogenase (LDH) 7130U/l. CT-scan of chest, abdomen and pelvis demonstrated diffuse supraclavicular, mediastinal, axillary, retroperitoneal, mesenteric adenopathy, omental caking, minimal peritoneal fluid and right inguinal lymph nodes. The palpable cervical lymph node was excised; pathology and flow cytometry were positive for CD-20 positive large B-cell NHL, so was the bone marrow aspirate (BMA), biopsy and flow cytometry on BMA. There was infiltration of the bone marrow as well as the lymph node with large atypical lymphocytes with high mitotic index showing positivity for CD 20 on immunohistochemistry. The patient was staged as IV B. Tumor lysis syndrome TLS was anticipated and patient was started on adequate hydration and alkalinization in addition to oral allupurinol. After 24, chemotherapy was started and it included rituximab (anti CD-20 monoclonal antibodies) and CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) was planned to start after rituximab. Before rituximab, dexamethasone 16m.g. i.v. was given. Shortly after that and while she was receiving other premedications, her condition deteriorated with shortness of breath and agitation. When we started low dose (50mg/h) of rituximab, her condition deteriorated more, so the rest of the dose was withheld and CHOP was not given. The patient’s condition deteriorated further with hypotension, tachypnea and deterioration of consciousness. Arterial blood gases (ABG’s) showed severe metabolic acidosis (pH of 7.10). The patient became anuric. Her laboratory studies were repeated and it demonstrated TLS with uric acid 0.19mmol/l, Bun 12.1mmol/l, creatinine 176.8mmol/l, potassium 7.3mmol/l, magnesium 1.1mmol/l, calcium 1.75mmol/l, phosphorus 4.68mmol/l, LDH 17800 u/l (Figure 1). The patient was intubated and started on aggressive hydration with fluids containing sodium bicarbonate, calcium gluconate and 25% dextrose with insulin. Urgent hemodialysis was employed and a brisk diuresis ensued after 18 h. Her parameters improved and she recovered fully with normal renal function after 3 days. Revaluation after the first cycle, which did not include CHOP, revealed bone marrow aspirate negative for lymphoma and CT-scans showed 70% reduction in the previously described lymphadenopathy. ATLS was formally described in 1980 in patients with Burkitt lymphoma. It was noted that tumor bulk, high serum LDH and inadequate urine output correlated with this complication. It is well known that in patients receiving allopurinol and undergoing diuresis and alkalinization of urine this complication developed less frequently. Our patient has all the criteria to suspect TLS (bulky disease, high LDH and renal impairment) and, despite all the measures taken, ATLS developed during steroid and rituximab therapy. This case represents the second reported case of rituximabinduced ATLS and the fifth case of steroid-induced ATLS in patients with NHL. Table 1 presents a review of all the reported cases. ATLS is a potentially fatal condition, even in solid tumors with bulky disease, if it is not recognized and promptly managed aggressively. Rasburicase, a new recombinant form of urate oxidase, is an acceptable alternative to allopurinol. It rapidly controls plasma uric acid concentrations in patients at high risk of TLS. Rasburicase is not available and was not used in this case. Patients with aggressive NHL should be monitored carefully for this complication. Despite all the preventive measures taken, still some of them will develop ATLS even on steroid or rituximab monotherapy. Most of the side effects of rituximab are somehow similar to The Hematology Journal (2003) 4, 222–224 & 2003 The European Hematology Association All rights reserved 1466-4680/03 $25.00