Katsura Kohata

Allogeneic hematopoietic stem cell transplant following chemotherapy containing L-asparaginase as a promising treatment for patients with relapsed or refractory extranodal natural killer/T cell lymphoma, nasal type

The prognosis of advanced extranodal NK/T cell lymphoma (ENKTL) is poor. Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been suggested to be a promising treatment for this disease, but its utility has yet to be established. Here we retrospectively analyzed five cases of ENKTL treated with allo-HSCT in our institute. After induction chemotherapy, disease status at allo-HSCT was second CR in three patients and refractory in two patients. All patients received a myeloablative conditioning regimen, and GVHD prophylaxis consisted of tacrolimus or cyclosporine with short-term methotrexate. Only one patient who received conventional induction chemotherapy developed severe complications, which needed long-term treatment, while others who received chemotherapy containing l-asparaginase did not have severe complications. There were no cases of treatment-related mortality, and all patients survived without disease for a median follow-up period of 1911 days. These results suggested that allo-HSCT following l-asparaginase-containing induction chemotherapy might improve the outcome of advanced ENKTL.

Acquired hemophilia A with sigmoid colon cancer : successful treatment with rituximab followed by sigmoidectomy

Acquired hemophilia A is a rare and potentially fatal condition of coagulopathy caused by autoantibodies against clotting factor VIII (factor VIII inhibitor). We report a case of a 63-year-old woman, who presented with a sudden onset of severe hemorrhagic tendency with exclusively prolonged activated partial thromboplastin time (APTT). She was diagnosed with acquired hemophilia A due to a decrease in factor VIII activity and a high titer of factor VIII inhibitor. Hemorrhage was well controlled by recombinant activated factor VII. Although the level of factor VIII inhibitor did not decline with prednisolone and cyclophosphamide, it became undetectable with rituximab. In parallel with controlling hemorrhage, malignancy, which may cause acquired hemophilia A, was searched for and sigmoid colon cancer was found. After the eradication of factor VIII inhibitor, surgical resection was performed uneventfully. Thereafter, acquired hemophilia A has been in complete remission without any additional therapy. The present case suggests the efficacy of rituximab for refractory acquired hemophilia A and the importance of the identification of underlying diseases that can cause acquired hemophilia A.

Extreme eosinophilia caused by interleukin-5-producing disseminated colon cancer

Eosinophilia is caused by various pathological conditions, and can be divided into two entities based on the mechanism of eosinophil proliferation: i.e., clonal proliferation of eosinophils (chronic eosinophilic leukemia) and reactive proliferation of eosinophils. Clonal proliferation of eosinophils often accompanies chromosomal aberrations resulting in the generation of specific fusion genes, such as FIP1-like1 (FIP1L1)-PDGFRa [1]. Reactive proliferation of eosinophils is caused by various underlying diseases, including malignant diseases, allergy, autoimmune diseases, and infection, although the underlying diseases are sometimes unidentified in certain patients (idiopathic eosinophilia) [2]. With the exception of clonal eosinophilia, the pathophysiology of eosinophilia is not fully understood. However, overproduction of stimulatory cytokines involved in eosinophil proliferation, such as interleukin-5 (IL-5), granulocyte–macrophage colony-stimulating factor (GM-CSF), and IL-3, by pathological conditions is thought to play an important role in the development of this disease [3]. Among malignant diseases, hematological malignancies, such as Hodgkin’s and non-Hodgkin’s lymphoma, have been shown to be the major underlying diseases of eosinophilia [4, 5]. Although there have been several reports describing eosinophilia associated with solid tumors, such as lung cancer, colon cancer, and hemangioendothelioma, the incidence is quite low, and the level of increase in eosinophil count is mild [5–8]. Here, we report a case of extreme eosinophilia caused by colon cancer producing IL-5. A 72-year-old woman was admitted to our hospital because of malaise lasting for 2 months. She had no history of allergic or parasitic disease. Laboratory findings on admission showed anemia, leukocytosis (WBC: 232100/ll) with elevated eosinophil count (eosinophils: 141580/ll), and abnormal coagulopathy consistent with disseminated intravascular coagulation (DIC) (Table 1). Genetic studies showed no evidence of FIP1L1-PDGFRa or BCR-ABL fusions. Chromosomal analysis revealed normal karyotype. Serum CEA, CA19-9, CA125, CA15-3, IL-2R, and PIVKA-2 levels were significantly elevated (Table 1). Among these tumor markers, the level of sIL-2R was markedly elevated. It has been reported that the level of IL-2 is correlated with the activity of hypereosinophilic syndrome [9]. The elevation of IL-2R level may be induced by activated T cells; however, it is possible that IL-2R is secreted from activated eosinophils, because eosinophils from hypereosinophilic patients were shown to express IL-2Ra [10]. Bone marrow biopsy revealed no evidence of hematological malignancy. Whole-body CT showed multiple tumors in the colon, liver, lung, and pelvis with pleural effusion and ascites. Colonoscopy revealed an ileocecal tumor, but biopsy failed to yield a definitive diagnosis. As further H. Kato K. Kohata J. Yamamoto S. Ichikawa K. Ishizawa H. Harigae (&) Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, Japan e-mail: harigae@mail.tains.tohoku.ac.jp

Myeloablative Cord Blood Transplantation for Adults With Hematological Malignancies Using Tacrolimus and Short-Term Methotrexate for Graft-Versus-Host Disease Prophylaxis: Single-Institution Analysis

We studied clinical outcomes of 25 adult patients with hematological malignancies who underwent cord blood transplantation (CBT) after a myeloablative conditioning regimen, including high-dose cytosine arabinoside (CA) (8 g/m(2)), cyclophosphamide (CY) (120 mg/kg), and total-body irradiation (TBI) (12 Gy). For graft-versus-host disease (GVHD) prophylaxis, all patients received a combination of tacrolimus and short-term methotrexate (sMTX). Neutrophil engraftment was achieved in 20 of 25 patients. Of the 22 evaluable patients, 2 and 7 had grades I and II acute GVHD, respectively, and only 1 developed grade III acute GVHD after discontinuation of tacrolimus due to encephalopathy. Chronic GVHD developed in 13 of 19 evaluable patients, including 4 with the extensive type. However, the Karnofsky scores of survivors at 1 year after CBT were 90% or 100%. Eight of 25 patients died of nonrelapse causes (n = 4) and relapse/progressive disease (n = 4); 17 patients are currently alive with 15 free of disease at the present time (median follow-up, 24 months). The probability of disease-free survival at 2 years among patients with standard risk was 89% and that of high-risk patients was 30%. Transplantation-related mortality within 100 days was 12%. These results suggested that the CA/CY/TBI combination is a promising conditioning regimen for myeloablative CBT. Furthermore, tacrolimus and sMTX seemed to have suppressed severe acute GVHD and chronic GVHD, which may also contribute to the favorable results.