Immune thrombocytopenia in association with acute lymphoblastic leukæmia and a haemophagocytic syndrome

To the Editor: Immune thrombocytopenic purpura (ITP) has been reported in association with various malignancies (1-6). Association with acute leukaemia is, however, uncommon. We report a case of severe refractory ITP in a young woman with acute lymphoblastic leukaemia and a haemophagocytic syndrome. In April 1992 an 18-year-old woman was admitted with acute lymphoblastic leukaemia (ALL) following 1 week of lethargy, postural dizziness and exertional dyspnoea. FBE on admission demonstrated haemoglobin 9.7 g/dl (12.0-16.0 g/dl) WCC 46.1 x 109/1 (4.0-11.0 x 109/1) blasts 35.5 x 109/1 platelets 24 x 109/1 (150-400 x 109/l). Bone marrow examination demonstrated numerous blasts, reduced haemopoiesis and granulopoiesis but normal megakaryocyte numbers. Histiocyte numbers were also increased. Following immunophenotyping and cytogenetics, the final diagnosis was ALL L2, pre B. Induction chemotherapy was initiated using vincristine, daunorubicin, prednisolone and L-asparaginase (7). In the post-induction period the patient developed neutropenic sepsis and marked glucose intolerance. The major problem, however, was persistent and severe thrombocytopenia. Little or no platelet increment was seen following daily platelet transfusions despite hydrocortisone premedication and the use of single donor HLA-matched platelet transfusions. Despite severe thrombocytopenia, repeat bone marrow aspirate and trephine on d 11 demonstrated the presence of plentiful megakaryocytes, with active erythropoiesis and increased histiocytes. The blast count was 4%. The patient required daily transfusion of 5 to 20 units of platelets until approximately 6 wk post-induction when the platelet count stabilised at 20-50 x 109/l. Eight weeks post induction the patient was readmitted with severe thrombocytopenia and associated skin bleeding. FBE revealed Hb 9.8 g/dl WCC 2.4 x 109/1 platelets 2 x 109/l. Bone marrow examination again demonstrated numerous megakaryocytes; the blast count was 6.4%. From the time of induction the patient had required repeated blood transfusions for anaemia, the aetiology of which was not clear. Faecal occult blood testing was negative, the patient was amenorrhoeic and investigations for haemolysis, including reticulocyte count, haptoglobin and LDH levels were normal. DIC screen anticardiolipin and antinuclear antibodies were negative. Intravenous gamma-globulin 400 mg/kg daily for 3 d was administered. Danazol, 200 mg daily and prednisolone 60 mg daily were also commenced. A second course of i.v. gamma-globulin was required following failure of the initial treatment and the platelet count subsequently rose to 20-30 x 109/1, at which time the patient was discharged. In July 1992 the patient was readmitted with anaemia and thrombocytopenia. FBE showed Hb 6.9 g/dl WCC 2.7 x 109/1 platelets 24 x 109/l. Bone marrow examination on this occasion revealed numerous megakaryocytes, erythroid hyperplasia and a marked increase in histiocytes, some of which showed erythrophagocytosis. Vinblastine 0.1 mg/kg via slow intravenous infusion was given weekly for 2 wk. Further treatment was prohibited by the development of neutropenic sepsis and severe jaw pain; however the platelet count increased and was maintained above 80 x 109/1 and no further blood or platelet transfusions were required. The patient was able to receive intrathecal methotrexate which had been delayed by persistent thrombocytopenia. The corticosteroid was gradually withdrawn. Consolidation chemotherapy was administered in October 1992 and is ongoing. Bone marrow examination in November 1992 showed a return to normal haemopoiesis with no further histiocytosis or erythrophagocytosis. The patient remains in remission with a platelet count within the normal range except for transient falls related to chemotherapy. This patient presents the difficult problem of severe thrombocytopenia occurring in the context of acute leukaemia. The aetiology is most likely to be immune as demonstrated by severe thrombocyto-