Masato Yagita

Peripheral neuropathies should be recognized as the adverse effects of biological agents, especially anti-TNF agents. However, no solid clinical databases for biological agent-associated peripheral neuropathies (BAPN) have been established in Japan. Here we report two cases of peripheral neuropathy associated with anti-TNF agents. One was peroneal motor neuropathy. The other case was chronic inflammatory demyelinating polyradiculoneuropathy. In addition, we summarize the previous reports on BAPN and discuss their prevalence rate, pathogenesis and management.

A 43-year-old woman with systemic sclerosis (SSc) developed IgA deficiency (IgAD) after cholecystitis. The severe decrease of IgA (+IgA⁺ and CD38⁺IgA⁺ cells were normally present. Although the mechanism of secondary IgAD is still vague, its association with autoimmune diseases including SSc and also with bacterial infection is discussed.

A 67-year-old man was referred to our hospital for treatment of hemophagocytic syndrome. Hypotension, hypoxemia, pleural effusion, severe anasarca, and splenomegaly were noticed at the time of admission. Laboratory findings showed anemia (7.7 g/dl), thrombocytopenia (4.5 x 10(4)/microliter), an increase of serum LDH (1,466 IU/L) and severe hypoalbuminemia (1.9 g/dl). Bone marrow aspiration revealed an increase of reticulum cells with active hemophagocytosis and the presence of immature lymphocytes (6.0%). Lymphoma was suspected, but effective chemotherapy could not be performed because of progressive hypoxemia and severe hypoalbuminemia, and the patient died of the disease 2 weeks after admission. Autopsy revealed large lymphoid cells packed within systemic vessels as well as invasion into organs such as the liver, lungs, and spleen. The postmortem diagnosis was intravascular large B-cell lymphoma. Hypoalbuminemia and hypoxemia appear to be important clinical features of intravascular large B-cell lymphoma.

A 41-year-old man was given a diagnosis with of acute promyelocytic leukemia (APL) in August 1994. A chromosome analysis showed 46, XY, t(15; 17) and 47, XY, idem, +8 at that time. Because initial induction chemotherapy (BHAC-DMP) has not been successful, the patient was given 45 mg/m2 of all-trans retinoic acid (ATRA) and achieved complete remission (CR) after 26 days on this regimen. Following intensified chemotherapy, he received an autologous peripheral blood stem cell transplant (PBSCT) with high-dose busulfan and cyclophosphamide in April 1995. Competitive RT-PCR for PML-RAR alpha mRNA did not find any of APL cells in the collected stem-cell fraction. Although the patient remained in CR without therapy, a myeloblastoma was found in his left external auditory canal in August 1996. Recurrence in bone marrow, moreover, was discovered the following month. A chromosome analysis of bone marrow cells showed 47, XY, t(15; 17), +8 at this time. Thus, the extramedullary relapse developed after autologous PBSCT. This case provides information linking ATRA to the development of extramedullary relapse in patients with APL.

We report a high risk of therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) in patients receiving oral administration of etoposide for recurrent breast cancer. We examined 119 patients with recurrent disease. Patients were initially treated with anthracyclines, cyclophosphamide, or cisplatin with or without radiation before etoposide treatment. Etoposide was used as the final drug in most cases. Twenty-four patients were treated with the oral administration of etoposide (50 or 100 mg/day for 5-7 days at 4-week intervals). Three cases of t-AML/MDS developed among those 24 patients exposed to etoposide. In contrast, the development of t-AML/MDS was not observed in the other 95 patients not treated with etoposide. Our data suggest that there is a substantial risk of secondary leukemia with oral administration of etoposide for a prolonged period as well as i.v. schedules.