[IgE-κ type multiple myeloma achieving complete response with novel agents].

IgE multiple myeloma (MM) is a rare subtype of MM characterized by an aggressive and poor prognosis. Although novel agents have improved the prognosis of MM, there are few case reports of IgE MM treated with these agents. A 53-year-old male patient presented with pain in the right rib and was diagnosed with IgE-κ MM. He was treated with multidrug chemotherapy, including bortezomib and lenalidomide, and underwent autologous stem-cell transplantation (ASCT). Finally, he achieved a complete response after the initiation of pomalidomide. In previous reports, majority of patients with refractory IgE MM treated with novel agents had a poor prognosis. In contrast, patients who were treated with novel agents from the beginning and underwent ASCT had a long-term survival. Overall, the use of novel agents as the first-line therapy is expected to improve IgE MM prognosis.

Effective control of skin reaction by air sandwich technique in a patient with IgE-κ myeloma treated with subcutaneous bortezomib injection.

A 53-year-old man initially presented with costalgia and was diagnosed with MM, based on the pathological findings. IgE monoclonal protein was detected by Serum protein electrophoresis (SPEP) and, surprisingly, IgE was elevated to 7,950,000 IU/ml. Monitoring the disease response during treatment, we employed quantification of serum M protein at SPEP, because IgE levels were found to be inaccurate and erratic. The patient was treated with CyBorD. He found injection site reactions to be very burdensome, due to extreme skin changes. The diameter of the hyperpigmentation area was 8 cm. To reduce the severity of this reaction, we used an air sandwich technique, and succeeded in ameliorating the skin changes.

Lower leukocytes at initial diagnosis may predict poor outcome of very late relapse of acute lymphoblastic leukemia.

We have reported a rare case of acute lymphoblastic leukemia (ALL) recurring 19 years after the first presentation. Since 1984, 36 relapse cases 10 years or more after the first diagnosis have been reported. All cases were childhood ALL with a low to standard risk. Twenty-six attained CR2, and 18 of them remained in sustained CR2. The sustained CR2 ratio was 80% without transplantation. Sustained CR2 ratio was significantly lower in patients with lower leukocytes (<10 x 10(9)l(-1)) at initial presentation. A very late relapse of ALL remains chemosensitive, and its prognosis is not unfavorable.

[Transient chromosomal abnormalities following autologous peripheral blood stem cell transplantation for acute myelogenous leukemia].

Twenty-three patients with acute myelogenous leukemia (AML) have received autologous hematopoietic stem cell transplantation (autoHSCT) in our institute from 1997 to 2005. Among them, 3 patients relapsed, and the other 4 patients (17%) showed cytogenetic abnormalities after the autoHSCT. In these 4 patients with AML1/MTG8 or CBFbeta/MYH11 AML, RT-PCR findings using bone marrow cells were all negative when a cytogenetic abnormality was detected. Myelodysplasia was not detected in the bone marrow and no abnormal findings were seen in the peripheral blood. Cytogenetic abnormalities were detected 12-48 months after AutoHSCT, which disappeared in three patients and decreased in the remaining one patient with a median follow up time of 51 months (30-72 months) after their detection. We present our finding together with a review of the literature on post-autoHSCT cytogenetic abnormalities not related to relapse or secondary leukemia/myelodysplastic syndrome.

Stable response after administration of stem cell factor combined with granulocyte colony-stimulating factor in aplastic anemia.

We report successful treatment with 25 microg/kg of recombinant methionyl human stem cell factor (SCF) combined with 400 microg/m2 of recombinant human granulocyte colony-stimulating factor (G-CSF) in 2 patients with aplastic anemia refractory to immunosuppressive therapy. In one patient, hemoglobin levels increased from 6.4 g/dL to 11.3 g/dL after 36 weeks of SCF/G-CSF treatment. Thereafter, the platelet count (24.0 x 10(9)/L) began to improve without the therapy, and as of week 272, the platelet count was 125.0 x 10(9)/L with a leukocyte count of 8.4 x 10(9)/L and a hemoglobin level of 12.9 g/dL. In the other patient, more than 3 years of SCF/G-CSF treatment ameliorated hemoglobin levels and platelet counts from 5.8 g/dL to 15.9 g/dL and 8.0 x 10(9)/L to 50.0 x 10(9)/L, respectively. After cessation of SCF/G-CSF treatment, the positive response was sustained, and the platelet count improved further to 71.0 x 10(9)/L as of week 242. These observations suggest the clinical benefit of SCF/G-CSF administration to patients with refractory aplastic anemia.

[Superior sagittal sinus thrombosis during remission induction therapy for acute lymphoblastic leukemia].

Superior sagittal sinus thrombosis (SSST) has been reported to be caused by coagulopathy following oral contraceptive therapy, DIC, infection around the sinus, compression from a tumor, infiltration of tumor, and an inherited deficiency of proteins C and S, but SSST associated with hematological malignancies and L-asparaginase (L-Asp) therapy is rare. We report a case of an adult patient with acute lymphoblastic leukemia (ALL) who developed SSST during the remission induction therapy. A 25-year-old man was admitted with left facial nerve palsy and, following bone marrow aspiration and lumbar puncture, he was diagnosed as having T-ALL with CNS involvement. He received a 1-AdVP regimen as remission induction therapy and intrathecal administration of methotrexate and cytarabine. On day 29, he had a generalized convulsion and SSST was demonstrated by imaging tests. Lymphoid malignancy (ALL in particular), the use of L-Asp, CNS involvement, and intrathecal chemotherapy might be risk factors for the occurrence SSST. When a patient with those factors develops any neurological symptoms, we should pay attention to the occurrence of SSST, as well as stroke or CNS involvement, though SSST is rare.

[Effective treatment with rituximab in two patients with Waldenström macroglobulinemia].

CD20 is usually expressed on tumor cells in Waldenström's macroglobulinemia (WM). We report on two patients who achieved good responses with rituximab treatment. A 78-year-old man had anemia and was referred to our hospital in 1997. On admission, IgM-kappa monoclonal protein was detected in the serum and the IgM level was 4850 mg/dl, leading to the diagnosis of WM. In 2002, he developed heart failure due to anemia, and was treated with rituximab. The IgM level decreased to about 200 mg/dl and remained unelevated for 2.5 years. The anemia also improved. < Case 2 > A 59-year-old man was found to have elevated serum IgM (4850 mg/dl) and came to our hospital in 1998. IgM-kappa monoclonal protein was detected in the serum and he was diagnosed as having WM. His IgM level had been controlled with cyclophosphamide administration, but elevated levels were noted again in 2004. He was given rituximab, and a partial response was obtained (IgM 995 mg/dl).

[Immunosuppressive therapy for adult aplastic anemia in a single institution study].

We evaluated the efficacy and long-term outcomes of immunosuppressive therapy (IST) in 50 adult patients with aplastic anemia at a single institution. Twenty-one patients who had not responded to the first course of IST or relapsed after the initial response to IST were retreated with the second course of IST with antithymocyte globulin. The response and relapse rate of the initial IST were 76.7% and 23.3%, respectively. The response rate of salvage IST was 61.9%. Overall survival at 10 years was 84.0%. Failure-free survival at 10 years was 62.0%. Clonal or malignant diseases developed in 2 patients. Early deaths due to bleeding or infection were observed only in elderly patients. We conclude that most patients with aplastic anemia treated with IST show hematologic improvement and excellent long-term survival.

[Effective treatment with rituximab in a patient with refractory idiopathic thrombocytopenic purpura].

A 75-year-old woman had an episode of sudden nasal and oral bleeding. After that, petechiae appeared on her entire body. She received a platelet transfusion, and was referred to our hospital. On admission, the platelet count was as low as 1.2 X 10(4)/microl, and the PAIgG level was slightly elevated. Bone marrow cellularity was low, with a normal count of megakaryocytes. Anti-glycoprotein IIb/IIIa antibody-secreting B cells in the peripheral blood and platelet-associated anti-glycoprotein IIb/ IIIa antibodies were significantly high, and the patient was diagnosed as having idiopathic thrombocytopenic purpura (ITP). She failed to respond to corticosteroids, splenectomy and other therapies, so we administered rituximab, anti-CD20 monoclonal antibody, 375 mg/m2 weekly for four weeks. After the second infusion of rituximab, the platelet count began to increase. The platelet count continued to rise until a peak count (15.0 x 10(4)/microl) observed after 2 weeks from the fourth infusion, and the response was maintained for 8 more weeks. The levels of anti-glycoprotein IIb/IIIa antibody-secreting B cells and platelet-associated anti-glycoprotein IIb/IIIa antibodies decreased after the administration of rituximab. Rituximab was effective in this case of refractory ITP.

[A family of acute intermittent porphyria].

A 62-year-old man who had twice received laparotomies for abdominal pain of unknown origin was admitted to our hospital with acute abdominal pain. His family history of acute intermittent porphyria (AIP) suggested that it arose from acute porphyria. We treated the patient with 5% glucose solution by i.v. drip infusion and his abdominal pain improved rapidly. Diagnosis of AIP was established by the demonstration of reduced erythrocyte porphobilinogen deaminase (PBGD) activity and a point mutation (CAG --> CGG) in a splicing site in intron 10/exon 11 in the PBGD gene by DNA analysis. For screening of AIP carriers in his family, we measured erythrocyte PBGD activity. Four of his seven children were successfully diagnosed as AIP carriers. This is the ninth AIP family report, in which a mutation in the PBGD gene was revealed by DNA analysis.

[Refractory idiopathic thrombocytopenic purpura].

Chronic refractory idiopathic purpura(ITP) is defined as ITP with persistent thrombocytopenia despite conventional initial management with corticosteroids and splenectomy. The goal of treatment is not cure of the ITP, but only to achieve a safe platelet count, which is arbitrarily assumed to be greater than 30,000/mm3. The risk for major bleeding seems great only when the platelet count is less than 10,000/mm3. There is no accepted algorithm for management of patients with chronic refractory ITP. Recently, more targeted therapies including rituximab, anti-CD40 ligand and Campath-1H have been evaluated in refractory ITP.

[Simultaneous occurrence of acute myeloid leukemia with multilineage dysplasia and multiple myeloma].

An 82-year-old woman was admitted to our hospital because of dizziness and petechiae. Peripheral blood examination showed severe anemia and thrombocytopenia. Bone marrow aspiration revealed 42% leukemic blasts positive for peroxidase with multilineage dysplasia, leading to a diagnosis of acute myeloid leukemia with multilineage dysplasia. The levels of the patient's marrow plasma cells increased to 12%, whereas serum levels of IgG, A, and M dropped. lambda type Bence Jones protein was detected on urine immunoelectrophoresis. The total urinary protein was 3, 960 mg/day. Bone scintigraphy detected multifocal uptake in the ribs. The diagnosis was multiple myeloma developing simultaneously with acute myeloid leukemia. Possible mechanisms for the occurrence of acute myeloid leukemia and multiple myeloma were discussed.

[Chronic myelogenous leukemia in cessation of therapy after sustained CCR with interferon].

In Ph(+) CML patients who achieved complete cytogenetic response (CCR) with interferon-alpha (IFN) treatment, how long the treatment should be continued has not well been investigated. We report here 2 CML cases who stopped the treatment after CCR had been sustained with IFN for 2-3 years. A 49-year-old male (case 1) achieved CCR 6 months after the initiation of IFN treatment. CCR had been maintained for 3 years, and then the treatment was ceased. CCR has been sustained without any therapy for 4 years. In this case, RT-PCR became negative half a year after achievement of CCR, and since then negative RT-PCR has been maintained. In case 2, a 50-year-old male, CCR was achieved after 8 years of IFN treatment, and maintained for 2 years. One month after cessation of the treatment, CML relapsed cytogenetically. In case 2, negative RT-PCR results were not maintained during the period of CCR. In case 1, the levels of T-cells for PR 1 were undetectable in the peripheral blood.