Acute pancreatitis induced by adult precursor B-cell acute lymphoblastic leukemia associated with complex cytogenetics.

To the Editor: We report the case of a patient with precursor B-cell acute lymphoid leukemia and poor cytogenetics who presented with acute pancreatitis related to leukemia.

The patient, a 42-year-old gentleman, presented with abdominal pain. Physical examination revealed tenderness in the epigastrium and a 6-cm mass in the left chest wall. Laboratory data revealed a white blood cell count of 7.0 k/uL, with 39% blasts, hemoglobin of 10.5 g/dL, and a platelet count of 84 k/uL. Calcium was 8.5 mg/dL, amylase 274 IU/L, and lipase was 356 IU/L. Computed tomography (CT) of the thorax and abdomen showed fat stranding and haziness around the pancreas, suggestive of acute pancreatitis (AP) along with a soft tissue mass in the left anterior chest. Bone marrow aspiration and biopsy showed hypercellular marrow, heavily infiltrated by lymphoblasts, which were predominantly precursor B lymphoblasts. Findings were compatible with precursor B lymphoblastic leukemia/lymphoma with aberrant CD33 expression.

Bone marrow cytogenetics revealed a complex pattern (47, XY, t(1;7), t(2;15), t(4;15), +8[2]/46, XY). FISH was negative for t(9;22) BCR-ABL. CT-guided biopsy of the soft tissue mass in the chest wall showed precursor B lymphoblastic leukemia/lymphoma. Despite conservative management of AP, his pancreatic enzymes continued to be elevated. After 10 days of admission, he was started on systemic chemotherapy (hyper-CVAD). His pancreatic enzymes started going down within a day of initiation of the chemotherapy, and normalized within 2 days of starting treatment.

Acute lymphoblastic leukemia (ALL) is a neoplastic disorder that is rapidly fatal if untreated. Approximately half of all adult patients with ALL have lymphadenopathy, hepatomegaly or splenomegaly. Other sites of extramedullary involvement include the testis, retina, and skin. (1,2) AP in association with ALL has been reported previously, but the connection was mainly related to chemotherapeutic agents, namely L-asparaginase. (3) There have been a few case reports of AP associated with hypercalcemia due to acute T-cell leukemia (ATLL), (4) and one case report documented invasion of the pancreas by ALL lymphoblasts in a case of ATLL. (5)

Our patient, who was diagnosed with precursor B-cell ALL, presented with AP and showed improvement with chemotherapy. The patient had normal serum calcium at presentation, and his pancreatic enzymes continued to be elevated for 10 days despite conservative management. He improved soon after starting the chemotherapy however, suggesting that the AP was associated with ALL. The fact that the patient had a subcutaneous mass in his chest wall, biopsy proven to be ALL, suggested that his leukemia was maintaining a tendency to involve extramedullary organs.

Such presentation generally indicates a poor prognosis. The presence of complex cytogenetics is also a poor prognostic factor, which may have contributed to this presentation.

We hypothesize that the main cause of his AP was pancreatic tissue invasion by acute precursor B-cell leukemia cells. Although autopsy studies have shown pancreatic involvement by ALL, it has been found only with T-cell ALL. To the best of our knowledge, our report is the first to show clinically proven AP related mostly to involvement of the pancreas by precursor B-cell leukemia.

In conclusion, AP associated with ALL is induced not only by chemotherapy or hypercalcemia, but can also be directly related to invasion of the pancreas by lymphoblasts.

Amr Hanbali, MD

Philip Kuriakose, MD

Division of Hematology/Oncology

Department of Internal Medicine

Ila Bansal, MD

Koichi Maeda, MD

Department of Pathology

Henry Ford Health System

Detroit, MI

References

1. Cave H, van der Werff ten Bosch J, Suciu S, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer-Childhood Leukemia Cooperative Group. N Engl J Med 1998;339:591-598.

2. Greaves MF. Aetiology of acute leukaemia. Lancet 1997;349:344-349.

3. Wlazlowski M, Celinska W, Maciejka-Kapuscinska L, et al. [Acute pancreatitis in children with acute lymphoblastic leukemia treated with L-asparaginase] Pol Tyg Lek 1994;49:296-297.

4. Mantadakis E, Anagnostatou N, Smyrnaki P, et al. Life-threatening hypercalcemia complicated by pancreatitis in a child with acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2005;27:288-292.

5. Mori A, Kikuchi Y, Motoori S, et al. Acute pancreatitis induced by diffuse pancreatic invasion of adult T-cell leukemia/lymphoma cells. Dig Dis Sci 2003;48:1979-1983.