[Improvement of hepatomegaly after treatment with autologous hematopoietic stem cell transplantation followed by bortezomib and dexamethasone in Bence-Jones protein κ-type of multiple myeloma with systemic amyloidosis].

A 51-year-old man was admitted to our hospital complaining of right upper quadrant abdominal and back pain. Severe hepatomegaly (six fingerbreadths) was detected by liver palpation. Blood test results showed cholestatic liver disease. He was diagnosed with amyloidosis by liver biopsy. Bone marrow aspiration revealed 15% of contents to be plasma cells. BJPκ was detected by urine electrophoresis. Therefore, he was diagnosed with the BJPκ type of multiple myeloma with systemic amyloidosis. The patient was treated with bortezomib, dexamethasone and high-dose melphalan with autologous peripheral blood stem cell transplantation. He achieved VGPR (very good partial response) after transplantation. Hepatomegaly improved but swelling persisted, and he was therefore treated with 1.3 mg/m(2)/day of bortezomib and 20 mg/day of dexamethasone on day 1 and day 15 in 28-day cycles. Upon finishing 22 cycles in June 2014, his liver had returned to normal size. Restoration of normal liver size after treatment is rare in cases with severe hepatomegaly due to systemic amyloidosis. We thus report our case with a review of the relevant literature.

Safety and effectiveness of low-dose lenalidomide therapy for multiple myeloma complicated with bortezomib-associated interstitial pneumonia.

A 78-year-old woman was diagnosed with multiple myeloma (MM: IgG κ type, stage IIIA, ISS III) at a nearby hospital in August 2010. High-dose dexamethasone therapy was ineffective, and she was treated with 2 courses of bortezomib. She was referred to our hospital with back pain and dyspnea in November. She was diagnosed with interstitial pneumonia (IP) and improved rapidly with steroid pulse therapy. Because the involvement of bortezomib was suspected in IP, lenalidomide therapy was selected for MM. Lenalidomide (15 mg) was administered for 2 courses. The patient achieved a PR and the treatment is still ongoing with a good response. According to the interim report on PMS (post-marketing surveillance), 3 of the 1,177 patients treated with lenalidomide developed IP. The dose level was 25 mg in 2 cases and 10 mg in 1 case. The outcomes of these patients were death in 1 case, not recovered in 1 case, and unknown in 1 case. When lenalidomide is used to treat bortezomib-induced IP, there are no rules or regulations about its dose level. In the present case, the dose of lenalidomide (15 mg) was based on the retreatment dose after bone marrow suppression. Low-dose lenalidomide therapy was effective and safe against MM with a bortezomib-associated lung disorder.

Calpain-7 binds to CHMP1B at its second α-helical region and forms a ternary complex with IST1.

Some intracellular proteins involved in the endosomal sorting complex required for transport (ESCRT) system have microtubule interacting and transport (MIT) domains and bind to ESCRT-III protein family members named charged multivesicular body proteins (CHMPs) at their C-terminal regions containing MIT-interacting motifs (MIMs). While two types of MIMs (MIM1 and MIM2) have been reported, CHMP1B has MIM1 and IST1 has both MIM1 and MIM2. Previously, we demonstrated that CHMP1B and IST1 directly interacted with a tandem repeat of MIT domains of calpain-7 (CL7MIT) and that autolytic activity of calpain-7 was enhanced by IST1 in vitro but not by overexpression of IST1 in HEK293T cells. In this study, we detected enhancement of autolysis of mGFP-fused calpain-7 by coexpression with CHMP1B and observed further activation by additional coexpression of IST1 in HEK293T cells. We found that CL7MIT interacted with the second α-helical region of CHMP1B but not with the canonical C-terminal region containing MIM1 in vitro. Co-immunoprecipitation assays demonstrated that the interaction between CL7MIT and CHMP1B and between CL7MIT and IST1 became stronger when IST1 or CHMP1B was additionally coexpressed, suggesting formation of ternary complex of calpain-7, IST1 and CHMP1B. Moreover, subcellular fractionation analyses revealed increase of calpain-7 in membrane/organelle fractions by concomitant overexpression of these ESCRT-III family member proteins.

[Systemic amyloidosis associated with IgD-λ multiple myeloma].

We describe here a case of systemic amyloidosis associated with IgD multiple myeloma. A 59-year-old man was admitted to our hospital in April 2009, because of macroglossia and swelling in both wrists and fingers. He had difficulty moving his limbs and was aware of peripheral neuropathy. Skin biopsy revealed extensive deposition of amyloidosis, which was positive by Congo red staining. Laboratory findings were as follows: serum electrophoresis revealed IgD λ monoclonal protein, and Bence-Jones protein was detected. Monoclonal IgD protein had a concentration of 727 mg/dl, and a bone marrow aspiration revealed 49.6% of plasma cells. These findings led to a diagnosis of IgD multiple myeloma with systemic amyloidosis. The patient was treated with MP (melphalan and methylprednisolone), high-dose dexamethasone and VAD therapy (vincristine, adriamycin and dexamethasone), but systemic amyloidosis progressed, and his general condition deteriorated. Coexistence of IgD multiple myeloma and systemic amyloidosis is rare, and accumulation of case reports is needed to gain a better understanding of this condition.

[Cyclic thrombocytopenia complicated with Sjögren syndrome and the mechanism of periodic platelet count fluctuation].

Cyclic thrombocytopenia is a rare disorder with periodic changes of the platelet count. We experienced a patient with cyclic thrombocytopenia and Sjögren syndrome (SS), and studied the mechanism of the cyclic changes of the platelet count. The patient, a 75-year-old woman, was referred to our hospital because of dry mouth, dry eyes, and severe thrombocytopenia. Her platelet count varied from 0.2 x 10(4)/microl to 22.7 x 10(4)/microl in 14-28-day cycles. Anti-SS-A/Ro antibody and Schirmer's test were positive. Histological examination of the salivary glands revealed infiltration of inflammatory cells, leading to the diagnosis of SS. There was an inverse relation between the platelet count and serum levels of PA-IgG. When the platelet count was low, the number of bone marrow megakaryocytes and the colony counts of CFU-Meg decreased. The serum thrombopoietin level increased at the nadir of the platelet count and decreased as platelets increased. After prednisolone therapy, her platelet count increased along with the improvement of sicca symptoms. These findings suggest that platelet fluctuation is due to the periodic increase of platelet destruction, as well as periodic failure of platelet production.