Uneventful splenectomy and cholecystectomy in a patient treated with anti-interleukin-6 receptor antibody therapy.

INTRODUCTION: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune responses, acute phase reactions, and hematopoiesis. In rodent models, IL-6 has been suggested to be one of the essential mediators for optimal acute phase responses to infection and tissue damage. However, in humans, the roles of IL-6 in acute phase responses after surgery remain poorly understood. CASE REPORT: We present the first case report of successful splenectomy and cholecystectomy in a severe autoimmune-associated hemolytic anemia patient during treatment with a humanized anti-IL-6 receptor antibody. DISCUSSION: This unique case suggests that IL-6 is not an essential cytokine to safely perform surgical intervention and to prevent postoperative complications and that surgical intervention may not be contraindicated but can be selected as a therapeutic modality in patients treated with anti-IL-6 receptor antibody therapy.

Bone marrow transplantation with a reduced-intensity conditioning regimen in a patient with Wegener granulomatosis and therapy-related leukemia.

We describe a patient with Wegener granulomatosis (WG) who underwent long-term cyclophosphamide treatment and thereafter developed acute myelogenous leukemia (AML). After the AML was induced into remission, the patient received an allogeneic stem cell transplant (allo-SCT) from his sibling after undergoing a reduced-intensity conditioning regimen. His clinical course shortly after allo-SCT was uneventful. No clinically apparent acute or chronic graft-versus-host disease developed. Repeated analysis of the peripheral blood lymphocytes after transplantation showed complete donor chimerism. The level of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) remained undetectable until 4 months after transplantation, when it began to increase. When the level of PR3-ANCA peaked, the patient suddenly presented with fever and joint pain, which later spontaneously resolved in parallel with the declining titer of PR3-ANCA. He is now in remission for both AML and WG at 22 months after transplantation. The patient's clinical course after allo-SCT may provide us with valuable information regarding the establishment of allo-SCT as a therapeutic option for WG.

Hypersensitivity to mosquito bites as a potential sign of mantle cell lymphoma.

Hypersensitivity to mosquito bites (HMB) is known to be an allergic reaction and also a skin symptom in some cases of natural killer cell leukemia/lymphoma associated with Epstein-Barr virus (EBV) infection. We describe a patient who had suffered from HMB for 5 years, and subsequently developed mantle cell lymphoma (MCL), which resembled chronic lymphocytic leukemia in the early phase. EBV monoclonality was not detected in lymph nodes by Southern blotting. Serum levels of interleukin-4 and IgE were increased, but they decreased and HMB disappeared when MCL was predominant. We consider that HMB may be a potential sign of MCL.

Humanized anti-interleukin 6 receptor antibody induced long-term remission in a patient with life-threatening refractory autoimmune hemolytic anemia.

Refractory autoimmune hemolytic anemia (AIHA) is associated with considerable rates of mortality. Interleukin 6 (IL-6) has been reported to play a role in the pathogenesis of AIHA. This report describes a patient with AIHA who was successfully treated with a humanized anti-human IL-6 receptor (IL-6R) monoclonal antibody (MoAb). He had experienced life-threatening AIHA and had received conventional therapy with corticosteroids, azathioprine, cyclophosphamide, cyclosporin A, melphalan, plasma exchange, and irradiation to his spleen. However, the patient's symptoms and laboratory data did not show a sufficient improvement. Because his serum IL-6 level was elevated, we attempted to block IL-6 signaling by using a humanized anti-IL-6R MoAb, MRA. With 8 mg/kg of MRA administration every 2 weeks, the serum hemoglobin level gradually increased and normalized within 4 months. After 2 years of MRA treatment, the disease activity was well controlled without adverse reactions. Anti-IL-6R MoAb can be a novel and effective therapeutic agent for AIHA.

The serum cytokine profiles of lymphoma-associated hemophagocytic syndrome: a comparative analysis of B-cell and T-cell/natural killer cell lymphomas.

To elucidate the differences in pathogenesis between lymphoma-associated hemophagocytic syndromes (LAHS) of the T-cell/ natural killer cell (T/NK) and B-cell (B) types, we comparatively analyzed the clinical features and serum cytokine profiles of 33 patients with LAHS registered in the Kyoto University Hematology/Oncology Study Group. The serum cytokine levels of each patient group (B-LAHS versus T/NK-LAHS) were expressed as the ratio of the median to the upper normal values of the respective cytokines and were as follows: 19.05 versus 13.99 for soluble interleukin 2 (IL-2) receptor, 0.67 versus 0.67 for granulocyte-macrophage colony-stimulating factor (GM-CSF), 0.64 versus 1.26 for G-CSF, 5.70 versus 3.61 for M-CSF, 1.54 versus 3.39 for interferon gamma (IFN-gamma), 13.17 versus 1.17 for IL-6, 6.88 versus 1.58 for tumor necrosis factor alpha (TNF-alpha), 0.71 versus 0.41 for IL-1beta, 1.99 versus 0.21 for IL-12, and 105.32 versus 29.65 for IL-10. The serum levels of IL-6, TNF-alpha, and IL-10 were significantly higher in the B-LAHS group, whereas those of IFN-y were significantly lower. These differences between the 2 groups may reflect a difference in the pathogenesis Higher serum levels of IL-6, TNF-alpha, and IL-10 may be derived at least partly from neoplastic B-cells themselves In addition, the extremely high serum levels of IL-10 suggest that a compensatory anti-inflammatory process may operate in both groups and give rise to a profound immunosuppressive state and a poor outcome.

[Significance of soluble interleukin-2 receptor alpha chain in the management of patients with malignant lymphoma: a multi-center study].

A multi-center series of 117 patients with malignant lymphoma were analyzed to evaluate the clinical significance of soluble interleukin-2 receptor alpha chain (sIL-2R alpha). The initial levels of sIL-2R alpha ranged from 277 U/ml to 22,800 U/ml with a mean level of 3,451 +/- 4,268 U/ml and a median level of 1,600 U/ml. The sIL-2R alpha levels of the diffuse lymphoma/intermediate-grade subtypes defined by the LSG classification/Working Formulation were higher than those of the follicular lymphoma/low-grade subtypes. There was a tendency for B-cell lymphomas to show higher sIL-2R alpha levels than T-cell lymphomas. The sIL-2R alpha level was correlated with the Ann Arbor clinical stage (I, II versus III, IV), presence or absence of B symptoms, and performance status (0, 1 versus 2, 3, 4) of the patients. The sIL-2R alpha levels were in good accordance with the four risk groups defined by the International Prognostic Indices. Of 21 patients whose tumor burden was serially measured, the coefficients of correlation between sIL-2R alpha and tumor mass were > 0.6 in 18 cases. Sixty-two patients achieved complete remission (CR) during the study; the initial and minimum sIL-2R alpha levels were lower than those of the non-CR patients. This study confirmed that sIL-2R alpha is a convenient and useful marker in the management of malignant lymphoma.