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Immunosuppressive therapies, including antithymocyte globulin and cyclosporine (CsA), are used for the treatment of aplastic anemia, but they reportedly cause lymphoproliferative diseases. Here, we report two cases of aplastic anemia in which diffuse large B-cell lymphoma developed during treatment with CsA. In both the cases, CsA was discontinued and combination therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone) plus the thrombopoietin receptor agonist eltrombopag was initiated. Furthermore, supportive care, including blood transfusion and granulocyte colony-stimulating factor, was provided. After six or eight courses of R-CHOP therapy, a complete metabolic response was achieved without serious adverse events. These cases illustrate the safety of combining R-CHOP with eltrombopag therapy in patients at a high risk of severe pancytopenia.

We report the case of a 58-year-old woman with multiple myeloma who relapsed after the first autologous peripheral blood stem cell transplantation. She was refractory to new drugs and underwent a haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) by administering post-transplantation cyclophosphamide (PTCy) after the second autologous peripheral blood stem cell transplantation. Neutrophil and platelet engraftment were achieved on days 22 and 55, respectively. Grade II cutaneous acute graft-versus-host disease was observed, which was resolved by systemic steroid treatment. Post-transplant bone marrow examination confirmed donor chimerism replacement and immunophenotypic complete response, and the patient is alive and disease-free. Although haplo-HSCT using PTCy for multiple myeloma has not been reported in Japan, it could be performed safely. Here, we report our results with literature review.

Immune thrombocytopenia (ITP) may occur following a viral infection. We report the case of a 30-year-old woman with thrombocytopenia who was subsequently diagnosed with ITP. Although she was asymptomatic, chest computed tomography (CT) showed ground-glass opacities in the lower lung regions. The patient had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time polymerase chain reaction (RT-PCR) test. She responded well to 400 mg/kg of intravenous immunoglobulin therapy. Coronavirus disease of 2019 or COVID-19 should be considered as a cause of ITP during the pandemic, and chest CT scans and RT-PCR tests should be performed in patients suspected of ITP.

The 2017 World Health Organization (WHO) classification states that acute promyelocytic leukemia (APL) always presents with strong myeloperoxidase staining. However, we herein report of a 40-year-old woman with the microgranular variant of acute promyelocytic leukemia presenting with weak myeloperoxidase (MPO) staining. The leukemic cells were morphologically similar to monocytic cells, showing distorted-shaped nuclei and weak MPO staining. However, flow cytometry revealed positivity of CD2, CD34, and human leucocyte antigen-DR (HLA-DR) and pointed toward a diagnosis of APL. PML-RARA mRNA detection finally led the patient to a definitive diagnosis. The patient achieved complete remission by induction chemotherapy including tretinoin, cytarabine and idarubicin, and no differentiation syndrome was observed.

A 72-year-old woman with chronic myeloid leukemia (CML) and cirrhosis complicated with blood blisters on her right upper arm and ascites was admitted. She presented with shock vital on admission. Initial gram staining of blood cultures showed gram-positive cocci in chains, suggesting streptococcal toxic shock syndrome (STSS). Amputation of the right upper arm was performed owing to necrotizing fasciitis. Despite continued antibiotic therapy and systemic management, the blood blisters rapidly spread to the skin of the whole body, and she died 41 h after admission. Blood and fluid cultures from the blisters showed group B streptococci. Reports of patients with leukemia complicated with STSS are rare, and all cases have followed fatal courses. Particularly in this case, various risk factors, such as neutropenia due to tyrosine kinase inhibitor, neutrophil dysfunction due to cirrhosis, and elderly CML, overlapped. In the future, we believe that the lives of patients with leukemia complicated with STSS may be saved by establishing treatment methods and determining the detailed pathogenesis of STSS.

We retrospectively analyzed 30 patients with myelofibrosis who had been treated with ruxolitinib at our hospital. Although dose reduction was required for 13 patients due to anemia or thrombocythemia, it was later possible to increase the dose of ruxolitinib in 10 patients (77%). A total of five patients became transfusion dependent. Among them, one patient who continued ruxolitinib therapy exhibited subsequent symptom improvement and reduction in splenomegaly while also becoming transfusion independent. Four patients whose platelet counts were50×10

Pregnancy with paroxysmal nocturnal hemoglobinuria (PNH) poses a high risk of thrombosis, maternal death, miscarriage, and premature infants. Eculizumab lowers complications for pregnancy with PNH. A proposed protocol for the management of pregnancy in women with PNH by The National Research Group on Idiopathic Bone Marrow Failure Syndrome (the Japanese Guideline) recommends patients to start eculizumab at an early stage of pregnancy if they have not been treated with eculizumab or continue eculizumab during pregnancy. A 31-year-old female with PNH who was transfusion-independent but had occasional hemolysis was treated with eculizumab after a missed abortion and soon conceived. During pregnancy, the patient had neither hemolysis nor thrombosis and gave birth to a healthy child without using heparin. Heparin was initiated soon after delivery and continued for six weeks because of the known high postpartum risk of thrombosis. No postpartum complications were observed. PNH is a rare disease with fewer cases of pregnancy reported. Hence, it is essential to accumulate cases of PNH with pregnancy to establish the validity of the Japanese Guideline.

A 73-year-old woman diagnosed with symptomatic multiple myeloma (MM; IgG-κ type, DS: IIIA, ISS: 2) was administered bortezomib plus dexamethasone (BD) therapy. Post BD therapy, although autologous hematopoietic stem cell transplantation and thalidomide, lenalidomide, and melphalan/prednisolone/thalidomide (MPT) therapies were also performed, the patient remained unresponsive. However, the disease relapsed, and she eventually developed pantalgia. Therefore, the patient was admitted to our hospital and was administered pomalidomide and dexamethasone (Pd) therapy. The serum amylase (AMY) and urine AMY levels were 6,329 and 6,098 IU/l, respectively, which were salivary gland-type amylase (S-AMY). Notably, the markedly high levels immediately decreased after the first course of the Pd therapy; additionally, the pantalgia also disappeared. The S-AMY level in the supernatant from cultured bone marrow mononuclear cells was higher than that observed in a normal control. In addition, AMY was high when MM previously relapsed, suggesting the presence of AMY-producing MM. Although AMY-producing MM was first reported by Hata et al. in 1988, few cases have been reported in the new-drug era. In conclusion, AMY-producing MM frequently, including in our case (as the patient was refractory to treatment), is difficult to treat. However, our patient positively responded to the novel next-generation drugs such as pomalidomide and carfilzomib.

Extranodal natural killer (NK) /T-cell lymphoma (ENKL), nasal-type, is an aggressive lymphoma that is relatively common in Asia and is resistant to anthracycline-based chemotherapy. Antigen-specific cytotoxic T-lymphocyte (CTL) therapy can induce durable remission in selected tumors, such as melanomas and virus-related tumors. ENKLs are commonly infected with the Epstein-Barr virus (EBV) ; therefore, CTL therapy can be effective for these lymphomas. However, CTLs that are continuously exposed to viral or tumor antigens usually get exhausted. Antigen-specific CTLs generated from iPSCs have a higher proliferative capacity and longer telomeres than original CTLs and are functionally rejuvenated (rejuvenated T cell, rejT). For clinical translation, the tumorigenic potential of iPSCs and the malignant transformation of differentiated iPSCs are major safety concerns. To address these issues, we introduced inducible caspase-9 (iC9) -based safeguard system into iPSCs. iC9-rejTs exert strong anti-tumor effects against EBV-infected tumors in vivo, and the iC9 suicide gene system provides a reliable safeguard for rejT therapy. We initiated a preclinical study using this novel immunotherapy for EBV-associated lymphoma. We believe that rejT therapy can be a potential safe approach as an "off-the-shelf" therapy for refractory ENKL in the future.

The JAK2V617F mutation is the commonest major genetic mutation of myeloproliferative neoplasms (MPNs) and has been defined in the WHO diagnostic criteria for MPNs. However, there is still no approved in vitro diagnostic test kit available in Japan. We evaluated a JAK2V617F allele quantification kit (test method) in a prospective, multicenter clinical performance study involving patients with MPNs who were diagnosed with polycythemia vera, essential thrombocythemia, and primary myelofibrosis; healthy volunteers were also included in the analysis. Good correlation was observed between the allele burden determined using the test method vs. that determined using next-generation sequencing (NGS) in the patient group (r=0.998, y=1.071x-0.069; n=156). Furthermore, all allele burdens in the healthy group (n=54) were below the lower limit of the measurement range of the test method (0.042%). Our results confirmed that the test method could quantitatively measure the JAK2V617F allele burden in patients with MPN. Thus, the novel JAK2V617F allele quantification kit can be considered useful for the diagnosis of MPNs.

Primary myelofibrosis (PMF) is commonly associated with anemia. IMiD

Pulmonary artery hypertension (PAH) has been reported to be a severe adverse event associated with dasatinib therapy. Among the 76 chronic myeloid patients who were treated with dasatinib at our hospital, six patients showed high estimated pulmonary arterial systolic pressure, as observed by echocardiography. PAH was confirmed using right heart catheterization in three (3.9%) patients with increased mean pulmonary artery pressure (mPAP). In one patient, although mPAP was higher than the normal range, it did not fulfill the criteria of pulmonary hypertension. After the discontinuation of dasatinib, BNP and dyspnea were improved in five patients. Therefore, it should be noted that dasatinib can cause PAH at higher rates than those reported previously, and if PAH is confirmed or suspected during dasatinib therapy, then dasatinib should be immediately discontinued.

The subject was an 83-year-old female; she had a history of Propionibacterium acnes-related sarcoidosis at the age of 79 years. At diagnosis, she was treated with clarithromycin and achieved remission. Four years later, during a routine physical check-up, she presented with pulmonary opacities and swelling of multiple lymph nodes. A definitive diagnosis of lymphoma could not be made by inguinal lymph node biopsy. The patient's general condition was good, and we observed her clinical course. Oh the 56th day of her illness, she died suddenly. Autopsy revealed diffuse large B-cell lymphoma (DLBCL). Sarcoidosis-lymphoma syndrome (SLS) was diagnosed after sampling hyalinized nodules from both lungs. The cause of death was organizing pneumonia around an epithelioid granuloma and cor pulmonale. Organization markedly increased around the DLBCL. These findings might be associated with cor pulmonale. Although SLS often appears during chronic active sarcoidosis, sudden death is rare and there are few reports on SLS in Japan. We report this case along with a review of the literature.

A 77-year-old man with myelodysplastic syndrome suffered from duodenal perforation after undergoing endoscopic submucosal dissection (ESD) for treatment of duodenal cancer. He presented with hemorrhagic shock, peritonitis and disseminated intravascular coagulation (DIC), and received transfusions of red blood cells (RBC), fresh frozen plasma (FFP), γ-globulin and albumin (Alb). One month after the last RBC transfusion, prolonged thrombocytopenia was observed, and platelet concentrate (PC) was transfused. However, immediately after starting PC transfusion, he developed dyspnea, hypotension and rash, and was thus diagnosed as being in anaphylactic shock. Analysis of the patient's serum revealed absence of haptoglobin (Hp) and the presence of anti-Hp antibody. Further studies, using PCR detected Hp

This review outlines recent advances in the understanding of gene alterations and the genetic background associated with myeloproliferative neoplasms (MPNs), as well as describing the roles of these genetic factors in the development of MPNs. JAK2, CALR, and MPL mutations that are specifically found in patients with MPNs have been shown to constitutively activate cytokine receptors. Other mutations that are commonly found in hematopoietic malignancies have been demonstrated to synergize with disease-specific mutations and to accelerate the development of MPN, or to define the disease subtype. However, some of these mutations are found in healthy elderly persons, such that the mechanism of MPN development remains elusive. Further analyses including those for genetic factors associated with the occurrence of MPN will lead to a complete understanding of MPN development.

Cardiac amyloid light-chain amyloidosis (AL amyloidosis) is a rare disease with a very poor prognosis, associated with plasma cell dyscrasias such as monoclonal gammopathy of undetermined significance and multiple myeloma. Though bortezomib-containing regimens have achieved high hematologic response rates, there are still few reports describing the outcomes of Japanese patients. Six patients with severe cardiac AL amyloidosis were treated with bortezomib-containing regimens. Involved free light chain (iFLC) decreased immediately in most of these cases. However, the condition of heart failure and N-terminal pro-B-type natriuretic peptide (NT-proBNP) worsened in the early phase of this treatment and then improved several months later. At 29 months, the median duration of follow-up (2-47months), all patients remain alive except one who died of sudden cardiac arrest. Bortezomib-containing regimens are considered to be among the effective treatments for severe cardiac AL amyloidosis.

TAFRO syndrome is a systemic inflammatory disorder characterized by low platelet counts, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly. Patients with TAFRO syndrome occasionally have courses complicated by immunological diseases. Herein, we describe a case of TAFRO syndrome associated with autoimmune hemolytic anemia (AIHA). The patient was admitted because of menorrhagia. She had thrombocytopenia, pleural effusion and ascites, hepatomegaly, and multiple lymphadenopathies. Her symptoms worsened, especially fever, pleural effusion and ascites, and she developed AIHA. Steroid pulse therapy followed by 45 mg of prednisolone (PSL) improved not only the symptoms of TAFRO syndrome but also those of AIHA. There have been no reports, to our knowledge, of AIHA associated with TAFRO syndrome, and detailed studies on this syndrome are needed.

To investigate the current situation and issues regarding the diagnosis of Philadelphia-negative myeloproliferative neoplasms (MPN) in Japan, we retrospectively analyzed an accumulated cohort consisting of 1,081 patients with suspected MPN. Based on WHO2008 diagnostic criteria, we diagnosed 101 of these patients with polycythemia vera, 179 with essential thrombocythemia, 36 with primary myelofibrosis, 45 with unclassifiable MPN, and 4 with myelodysplastic syndromes. Out of 716 patients, 235 were not diagnosed with MPN despite the detection of a JAK2, CALR, or MPL mutation. Among 156 patients with undefined MPN receiving further follow-up, none underwent bone marrow examination and screening for BCR-ABL1 was not performed in 88 cases. Thus, diagnosis was not possible in these cases due to a lack of essential examinations. Since the prognosis and treatment strategy associated with MPN differ among disease types, in addition to mutation analysis, the importance of bone marrow examination and screening for BCR-ABL1 must be re-recognized.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disorder that presents with hemolytic anemia, thrombosis, and bone marrow failure. Stressors such as infection and pregnancy have been known to exacerbate hemolysis in PNH patients. Surgery can also trigger prominent complement activation and is an important risk factor for hemolysis. Furthermore, the postoperative thrombosis risk is high. Eculizumab, which is a humanized monoclonal antibody against C5, suppresses hemolysis and prevents thrombosis, and thus improves quality of life for PNH patients. However, few reports have focused on eculizumab-treated PNH patients undergoing surgery. We report a 79-year-old PNH patient receiving eculizumab treatment who underwent three consecutive orthopedic surgeries requiring general anesthesia. Perioperative management was carried out routinely, as in non-PNH patients, and no postoperative complications developed. Surgery was formerly considered to be a high risk event for PNH patients, but this case raises the possibility that even elderly PNH patients may undergo surgery safely when maintained on eculizumab treatment.

We report an 81-year-old woman with multiple myeloma who developed acute cardiac injury after receiving bortezomib. The patient received weekly intravenous bortezomib. She developed shortness of breath and bilateral pedal edema on day 19. Electrocardiography showed no ST-T changes but the cardio-thoracic ratio was increased, the ejection fraction was decreased, the ventricular septum showed hypokinesis and mitral regurgitation was noted. We stopped bortezomib and started acute congestive heart failure treatment. ST-T changes were detected after the patient's condition improved. There was no evidence of coronary stenosis on CT angiography. Acute cardiac injury is rare during bortezomib administration, but patients should be monitored carefully during treatment.

A 36-year-old woman with a left lung tumor was referred to our hospital since a pathological diagnosis had not been obtained at a previous medical institution. We carried out CT-guided percutaneous lung biopsy with an 18-gauge needle and obtained four samples. Immunological staining revealed the specimens to be CD30- and PAX5-positive, with large dysplastic lymphocytes negative for Bob-1 and Oct-2 with a background of small lymphocytes and eosinophils. Primary pulmonary Hodgkin lymphoma (PPHL) was diagnosed. Although PPHL is very rare, it should be included in the differential diagnosis of lung tumors and immunological staining with CD15 and CD30 is recommended. Furthermore, carefully planned CT-guided lung biopsy is useful for diagnosing PPHL.

A 78-year-old man with liver cirrhosis was admitted to our hospital because of persistent diarrhea and abdominal pain. Colonoscopy revealed erosions and submucosal tumors in portions of the sigmoid colon and rectum, which were diagnosed as mantle cell lymphoma with biopsy. After chemotherapy consisting of vincristine and prednisone, he developed Aeromonas hydrophila septicemia, resulting in septic shock and necrotizing fasciitis despite prescribing antimicrobial agents to which this organism was susceptible. Whenever we intend to treat patients with hematological malignancies and an underlying chronic liver disease, we must keep this bacterium in mind.

A 68-year-old female presented with shortness of breath. Chest radiography showed pleural effusion in the right side only. She was suspected of having ovarian cancer because CA125 levels were increased in the pleural effusion, and she consulted our hospital. A chest CT scan showed right pleural nodular lesions. Thoracoscopic pleural resection was performed. Histologic examination of a biopsy specimen showed the diffuse infiltration of small∼medium, mature lymphocytes. These lymphocytes were found to be positive for CD20 and CD79a, but negative for CD3 by immunohistochemistry. These results were interpreted as being consistent with a diagnosis of mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). She commenced chemotherapy with R-CHOP, and the pleural effusion disappeared. MALT lymphoma arising in the pleura is very rare, with only 12 published cases, and most cases have been described in Japan. CA125 levels correlated with the stage, tumor bulk, and presence of effusion. This patient exhibited a high level of CA125 that decreased with therapy.

Romiplostim is a thrombopoietin (TPO) receptor agonist that has attracted attention as a novel drug for the treatment of refractory immune thrombocytopenia (ITP). However, bone marrow reticulin and collagen fibrosis during the long-term use of romiplostim has recently become a concern. Here, we present a patient with ITP who exhibited bone marrow fibrosis after the completion of a Japanese phase III clinical trial and long-term extension study of romiplostim. The patient was a 64-year-old woman. She was diagnosed with refractory ITP and participated in a clinical trial of romiplostim. Myeloblasts were found in her peripheral blood in Week 116 of treatment with romiplostim in the long-term extension study, and romiplostim was discontinued. In Week 118, teardrop cells appeared and she underwent a bone marrow biopsy. Results showed reticulin and collagen fiber hyperplasia and her platelet count decreased markedly to 0.4×10(4)/μl with macroscopic hematuria. Thereafter, a reduced dose of romiplostim was resumed. Approximately one year after the resumption of romiplostim, a bone marrow biopsy revealed a decrease in reticulin and collagen fibrosis. Although few patients exhibited bone marrow fibrosis with TPO and the event may be reversible, our observations indicate that careful monitoring is required for general clinical use.

We report a 44-year-old man with acute lymphoblastic leukemia (ALL) presenting with fever and lymphadenopathy. Induction chemotherapy was initialed according to the JALSG ALL202 protocol, and L-asparaginase (L-asp) was given on days 20, 22, and 24 of therapy. Abrupt elevations of liver transaminase and bilirubin levels were observed on day 26. On day 30, coagulopathy and hepatic encephalopathy appeared. He was diagnosed with fulminant hepatitis and plasma exchange was performed, but he died on day 32, possibly due to L-asp-induced hepatitis. The common side effects of L-asp are hypersensitivity, ammonemia, coagulopathy, pancreatitis, convulsions, anaphylaxis, hepatotoxicity, and thrombosis. Although rare, reports of deaths due to hepatic failure during treatment with L-asp exist. L-asp is currently used for treatment of a wide range of hematological malignancies such as ALL and NK/T-cell lymphoma. A retrospective analysis of patients treated with L-asp should be carried out to elucidate the incidence and risk factors of liver dysfunction and fulminant hepatitis during L-asp treatment.

A 26-year-old female progressed to blastic crisis (BC) after three months administration of imatinib for chronic myelogenous leukemia (CML) chronic phase (CP) and was treated with a dasatinib containing chemotherapy regimen. After remission to second CP, she was hospitalized because of fever and hemorrhagic diarrhea during dasatinib maintenance therapy. She was diagnosed as having cytomegalovirus (CMV) colitis because CMV antigen in blood leukocytes was positive and CMV-positive cells were also detected on staining of an ileocecal mucosal biopsy specimen with an anti-CMV antibody. Although blood leukocyte CMV antigen and CMV staining in colonic mucosa became negative after ganciclovir treatment, hemorrhagic diarrhea did not improve. However, after discontinuance of dasatinib, hemorrhagic colitis drastically improved and did not recur after administration of nilotinib. It is possible that hemorrhagic diarrhea occurred due to dasatinib-related hemorrhagic colitis. Previous case reports have indicated that CD8-positive T-lymphocytes infiltrate the colonic mucosa in dasatinib-related hemorrhagic colitis, and the same pathological findings were seen in our case. Dasatinib may cause hemorrhagic colitis via immunological mechanisms in CML. Dasatinib-related gastrointestinal bleeding is less frequent in Japan compared to that in western countries, and Japanese cases diagnosed as having hemorrhagic colitis are extremely rare.

A 67-year-old woman with refractory multiple myeloma was admitted to our hospital for salvage therapy. She developed fever several days after chemotherapy was initiated and complained of chest pain. Since abnormal electrocardiogram was demonstrated. Emergency coronary angiography was performed, but the coronary artery did not demonstrate stenosis. Thereafter, the patient was diagnosed as having takotsubo cardiomyopathy. Hydragogue and nitric acid preparation transiently improved chest symptoms, but high fever persisted despite antibiotic and antifungal agents. She died on the 9th day after the initiation of chemotherapy. Physicians need to be aware that cardiomyopathy may develop as a severe side effect of chemotherapy.

We evaluated the clinical course of acute myeloid leukemia (AML) and the levels of WT1 mRNA in 191 AML patients. Of 114 previously untreated patients with AML, 107 cases were positive for WT1 mRNA (93.9% : 107/114). WT1 mRNA expression-levels declined to below 50 copies/microg RNA ("negative") after remission was achieved in all 66 patients who achieved remission and 84.8% (47/54) cases were "negative" at the end of the follow-up periods. On the other hand, WT1 mRNA was expressed in 87.0% of non-remission cases (47/54), maintaining 50 copies/microg of RNA or higher ("positive"). In all 29 cases who relapsed during the follow-up observation period after achieving remission, WT1 mRNA levels declined transiently approximately around the time of achieving remission and then rose again when the disease relapsed. Moreover, we determined the time of elevation of WT1 mRNA in 29 relapsed cases. In 79.3% of relapsed cases (23/29), WT1 mRNA levels rose above 200 copies/microg RNA, 43 days (median) before the diagnosis of "relapse". Given the percent of the correct diagnosis, WT1 mRNA at 200 copies/microg RNA appeared to be a reasonable cut-off level for early detection of AML-relapse. The WT1 mRNA level reflected the clinical condition. Taken together, these findings indicate that WT1 mRNA levels allow us to detect the presence of so-called "minimal residual disease" (leukemic cells) that cannot be detected by morphological examination. Besides these promising data, this kit is suitable for routine monitoring of AML because this kit utilizes peripheral blood as a test specimen, reducing the patient's burden at the time of collection of clinical samples as compared with bone marrow aspirate.

We investigated the prevalence of Helicobacter pylori infection and the effect of eradication therapy in patients with idiopathic thrombocytopenic purpura (ITP). H. pylori infection was found in 9 of 11 patients (81.8%). H. pylori eradication was obtained in all patients and significant platelet recovery was found in 5 of 9 patients (55.6%). One patient required re-eradication therapy because the urea breath test remained positive after the first therapy. After complete eradication, long time remission was obtained. The results suggested that the platelet count might be correlated closely with the amount of H. pylori in some patients with H. pylori positive ITP.

A 16-year-old male was referred to our hospital in April 2003 due to severe knee joint pain from five months previously. Lymphoblasts were identified in his peripheral blood, resulting in a diagnosis of acute lymphoblastic leukemia (ALL). Bone marrow examination revealed massive necrosis with clusters of lymphoblasts and the bcr/abl fusion gene. Magnetic resonance imaging (MRI) of the knee joint showed low signal intensity on T1-weighted images, and peripheral rim enhancement on Gd-DTPA enhanced fat suppression images, which was compatible with bone marrow necrosis. After the patient achieved complete remission (CR), the knee joint pain has disappeared. He was treated with an allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor and has been in CR for 26 months after the diagnosis of ALL. In the knee joint, the replacement of fatty marrow after BMT has been confirmed with MRI. Hematological malignancies including ALL should be considered in the cases of bone marrow necrosis and adequate treatment may improve necrosis.

A 56-year-old woman with acute myeloid leukemia had two rapidly growing necrotizing nodules with ulcer formation on her head after the first course of consolidation therapy. Clinical features corresponding to sepsis (e.g., fever) appeared following the development of the skin lesion. Pseudomonas aeruginosa was isolated from the blood as well as pus of the lesion. Based on these findings, a diagnosis of ecthyma gangrenosum was made. Treatment with ciprofloxacin and gamma-globulin dramatically improved the patient's clinical features. Since Pseudomonas sepsis with ecthyma gangrenosum is associated with a high mortality rate, it is important to start immediate treatment with appropriate antibiotics.

A proteasome inhibitor with a new molecular target (PS-341: bortezomib) was recently developed, and its efficacy in the treatment of refractory multiple myeloma has been reported in the United States. Here, we present a 54-year-old Japanese male patient with refractory multiple myeloma resistant to thalidomide. In 1998, the patient was diagnosed as having multiple myeloma (IgG-kappa) and underwent chemotherapy, autologous hematopoietic cell transplantation and interferon therapy, but the disease recurred. In December 2002, thalidomide and high-dose dexamethasone therapy was initiated, and while this combination therapy was effective at first, the multiple myeloma became unresponsive. On 23 June 2003, bortezomib therapy with the following regime was therefore started: 2.2 mg (1.3 mg/m2) of bortezomib was injected intravenously on days 1, 4, 8 and 11, and after a one-week break, another cycle was performed. Starting on day 8 of the administration, the serum total protein, IgG, serum calcium and LDH levels decreased rapidly, and after day 45 of the administration, blood transfusion was no longer needed. Since this is the first report of the use of bortezomib in the treatment of refractory multiple myeloma in Japan, further monitoring of this patient will provide extremely valuable information for developing a therapy against this disease.

A 35-year-old male with chronic myeloid leukemia in the accelerated phase received a peripheral blood stem cell transplant from his HLA-DR-mismatched mother. Graft-versus-host disease (GVHD) prophylaxis was with short-term methotrexate and tacrolimus. After transplantation, grade II skin acute GVHD occurred and was unsuccessfully treated with bolus methylprednisolone administration. The acute GVHD progressed to grade III of the skin, gut and liver, and mycophenolate mofetil (MMF) was accordingly administered at a daily dose of 2 g. This treatment resulted in a dramatic improvement in the clinical features of the acute GVHD. The patient suffered from hemorrhagic cystitis and several episodes of cytomegalovirus antigenemia. MMF may be useful for steroid-resistant acute GVHD despite an increasing risk of viral infections.

A 71-year-old man visited our hospital complaining of fever and a bleeding tendency. The peripheral blood WBC count was 10,400/microliter with 90% promyelocytes. The bone marrow was hypercellular with 88% promyelocytes. Disseminated intravascular coagulation was recognized. The patient was diagnosed as having acute promyelocytic leukemia and was treated with daily oral administration of all-trans retionic acid (ATRA) (45 mg/m2/day) and cytarabine (160 mg/day, intravenous drip infusion for the initial five days). The ATRA treatment induced leukemic cells to undergo mature myeloid differentiation. On day 24 after the start of treatment, the WBC count rapidly increased and acute myocardial infarction appeared, with consciousness disturbance and bilateral Babinski reflex appearing three hours later. Magnetic resonance imaging showed a fresh lacunar infarction of the right lenticular nucleus, and serum levels of IL-6 and PAI-1 were found to be elevated at the onset of infarction. Since there was a possibility that the retinoic acid syndrome (RAS) might have helped bring about the infarctions, we stopped the ATRA treatment and started administration of methyl-prednisolone (500 mg/body/day for 3 days) and gabexate mesilate. The WBC count decreased immediately and the consciousness disturbance improved. In this case, ATRA treatment might have initiated the RAS and resulted in some endothelial damage, thus causing the infarctions.

The hairy cell leukemia prolymphocytic variant, a subtype of hairy cell leukemia, is an extremely rare disease, especially in Japan. We report a case in which treatment with 2'-deoxycoformycin (DCF) improved the clinical features of the disease. The patient, a 70-year-old female, was first treated with 2-chlorodeoxyadenosine, but showed only transient improvement in the hematological findings. DCF was then administered every week. Following the start of this treatment, the leukemia cell count rapidly decreased and the platelet count simultaneously increased. This effect of DCF has so far been long term. More clinical studies are needed to confirm the therapeutic value of DCF.