Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in allogeneic hematopoietic stem cell transplant recipients: An observational study.

BACKGROUND: The effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients. METHOD: This prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination. RESULTS: A humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120-643) BAU/mL and 532 (95% CI 400-708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded. CONCLUSION: Messenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely.

Upfront allogeneic hematopoietic cell transplantation (HCT) versus remission induction chemotherapy followed by allogeneic HCT for acute myeloid leukemia with multilineage dysplasia: A propensity score matched analysis.

The efficacy of induction chemotherapy before allogeneic hematopoietic cell transplantation (HCT) for patients with acute myeloid leukemia with multilineage dysplasia (AML-MLD) is unclear. Some patients with AML-MLD have received upfront HCT without prior induction chemotherapy. To compare the transplant outcomes between patients who received upfront HCT and those who received induction chemotherapy followed by allogeneic HCT for AML-MLD, we retrospectively analyzed the Japanese registration data of 1445 adult patients who had received allogeneic HCT between 2007 and 2016. Propensity score matching identified 269 patients in each cohort. There were no significant differences in overall survival between the two groups. The cumulative incidence of leukemia-related mortality was significantly lower in patients who received upfront HCT than those who received induction chemotherapy before HCT. In the subgroup analyses, upfront HCT had a significantly reduced incidence of leukemia-related mortality among patients aged between 60 and 70 years, those with a lower white blood cell count at diagnosis (<3000/µL), and poor cytogenetic risk, and those who received myeloablative conditioning and cord blood transplantation. Our results suggested that induction chemotherapy before HCT did not have any benefits of survival after HCT for AML-MLD. Upfront HCT contributed to the reduced incidence of leukemia-related mortality after HCT. Upfront HCT should be considered for patients with AML-MLD who are eligible for allogeneic HCT.

[Successful treatment with lenalidomide-containing regimen of plasma cell leukemia accompanied by meningeal involvement].

The central nervous system (CNS) is rarely involved in plasma cell neoplasms (PCN), especially in patients with advanced disease, harboring poor prognostic chromosomal abnormalities. The prognosis after development of CNS is poor, with a median survival of 2-6 months. Here, we present a 56-year-old woman with isolated CNS relapse of plasma cell leukemia who was admitted to our hospital with back pain, thigh pain, and dysuria. Morphological examination of the cerebrospinal fluid (CSF) confirmed the presence of relapsed plasma cell leukemia, whereas active myeloma lesions were not detectable outside the CNS. Her symptoms did not improve with high doses of methotrexate or intrathecal chemotherapy. However, one cycle of combination therapy with lenalidomide and dexamethasone led to the improvement in clinical symptoms, with complete response seen in the CSF morphology. After 13 cycles, she developed a hematological relapse but maintained complete response in the CSF. The efficacy of lenalidomide in CSF PCN was sporadically reported, and the CNS penetrance of lenalidomide was demonstrated in animal models; however, its efficacy in CNS PCN has not been established. The current case supports the efficacy of combination therapy with lenalidomide as a new therapeutic strategy for CNS PCN.

[Mitoxantrone, etoposide, and cytarabine combination therapy for acute myeloid leukemia patients failing to achieve a complete remission after induction chemotherapy: a single-center experience].

Optimal salvage chemotherapy has not been established for patients with acute myeloid leukemia (AML) who fail to attain complete remission (CR) after one course of induction chemotherapy. This retrospective study aimed to assess the efficacy and safety of an MEC (mitoxantrone, 6 mg/m2, 1-3 days; etoposide, 80 mg/m2, 1-6 days; cytarabine, 1 g/m2, 1-6 days) regimen in patients with AML who failed to attain CR after one course of induction chemotherapy. Twenty-four patients were included in this study (median age, 58 years; range, 28-79 years). After one course of MEC, 11 patients (45.8%) attained CR. Febrile neutropenia was observed in all patients, and acute infection was observed in 7 patients (29.2%). However, no therapy-related death occurred. All patients eligible for transplantation and who attained CR after MEC salvage chemotherapy underwent allogeneic hematopoietic stem cell transplantation. The MEC regimen exhibited a good response rate with tolerable adverse events. Therefore, the MEC regimen can be safely used as a salvage treatment for patients with AML who failed to attain CR after one course of induction chemotherapy.

Utility of a simple prognostic stratification based on platelet counts and serum albumin levels in elderly patients with diffuse large B cell lymphoma.

Few studies have examined the prognostic impact of blood markers [other than the five factors in the enhanced International Prognostic Index (NCCN-IPI)] in elderly patients with diffuse large B cell lymphoma (DLBCL). We retrospectively analyzed 391 DLBCL patients receiving rituximab plus anthracycline-containing chemotherapy to examine the prognostic impact of simple blood markers. The NCCN-IPI was more accurate for discriminating prognoses than the original IPI. Multivariate analysis identified platelet count (<100,000/µl) and albumin (<3.5 g/dl) levels as significantly associated with lower overall survival (OS), independently of the NCCN-IPI. These parameters stratified patients into three risk groups: platelet-albumin (PA) score low (platelet count ≥100,000/µl, albumin ≥3.5 g/dl, n = 243); intermediate (platelet count <100,000/µl, albumin ≥3.5 g/dl or platelet count ≥100,000/µl, albumin <3.5 g/dl, n = 125); and high (platelet count <100,000/µl, albumin <3.5 g/dl, n = 23). The 5-year OS rates were 81.5, 48.6, and 20.2 %, respectively (p < 0.001). Notably, most patients with a low platelet count (n = 30) were stratified into the high-risk subgroup, suggesting that platelet count was prognostic for high-risk patients with a dismal outcome. In elderly patients (n = 291), the prognostic value of the NCCN-IPI might be diminished because the low-risk category was excluded; however, the PA score was predictive of survival: the 5-year OS rates for PA score low (n = 171), intermediate (n = 101), and high (n = 19) groups were 77.6, 47.9, and 19.0 %, respectively (p < 0.001). Platelet count and albumin levels are useful prognostic factors, and their combined use can predict survival, even in elderly patients.

Serum IgA level, monocyte count, and international prognostic index are independently associated with overall survival in patients with HTLV-I-negative nodal peripheral T cell lymphoma.

Peripheral T cell lymphomas (PTCL) account for 10-15 % of non-Hodgkin's lymphomas and are associated with poor prognosis. Although many prognostic factors for PTCL have been proposed, the heterogeneity of PTCL seems to be an obstacle in the establishment of clinically useful prognostic system, such as the International Prognostic Index (IPI) in diffuse large B cell lymphoma. PTCL with nodal manifestation include the HTLV-I-negative histologic subtypes of PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL). As PTCL-NOS encompasses a group of similar tumors and mostly shares their clinical pictures, we retrospectively analyzed clinical data from 77 patients diagnosed with ALCL, AITL, and PTCL-NOS at Kobe City Medical Center General Hospital from May 1994 to February 2012 to identify the prognostic factor for nodal PTCL. The median age of patients was 64 years, ranging from 23 to 83 years. With a median follow-up of 50 months, 5-year overall survival (OS) was 43 %. Multivariate analysis identified high-risk IPI (hazard ratio (HR), 4.04; P = 0.015), absolute monocyte count > 0.8 × 10(9)/L (HR, 3.44; P = 0.001), and serum concentration of IgA > 410 mg/dL (HR, 2.31; P = 0.013) as poor prognostic factors for OS. Thus, we have identified novel prognostic factors of monocyte count and serum IgA level for nodal PTCL. Although conventional prognostic models mainly reflect both tumor characteristics and host factors, the present model indicates the importance of host immune response as the unfavorable prognosis.

IP-10/CXCL10 and MIG/CXCL9 as novel markers for the diagnosis of lymphoma-associated hemophagocytic syndrome.

Lymphoma-associated hemophagocytic syndrome (LAHS) is a serious disorder, and its early diagnosis and treatment with appropriate chemotherapy are very important. However, reliable markers for early diagnosis of LAHS have not been identified. We screened serum cytokines using a newly introduced assay system, cytometric bead array (CBA), and identified interferon-inducible protein 10 (IP-10)/CXCL10 and monokine induced by interferon gamma (MIG)/CXCL9 as useful markers. Serum concentrations of IP-10 and MIG at the time of LAHS diagnosis were greater than 500 and 5,000 pg/ml, respectively. The sensitivity and specificity for LAHS diagnosis were 100 and 95 %, respectively, when we set the above values as the cut-off levels. Serum levels of these two chemokines were already elevated at the time of admission and significantly decreased after successful treatment, indicating their usefulness for both the diagnosis and therapeutic outcomes for LAHS. IP-10 and MIG were also useful in distinguishing severe from moderate/mild LAHS, and B-cell-type LAHS from T-cell/natural killer cell-type LAHS. Furthermore, IP-10 and MIG were of use to distinguish LAHS from sepsis in patients with hematologic malignancies. Rapid measurement of IP-10 and MIG by CBA appeared to be important for early diagnosis and treatment of LAHS.

Simultaneous thrombosis of the mesenteric artery and vein as a novel clinical manifestation of intravascular large B-cell lymphoma.

A 79-year-old man with a 2-month history of fever and weight loss was admitted to our hospital because of an acute abdomen. Abdominal CT scans showed marked sectional thickening and edema of the small intestine. On laparotomy, a 16-cm section of the small intestine was ischemic and necrotic; therefore, segmentectomy of the intestine was performed. A thrombus was noted at the stump of the mesenteric artery branch. Histopathological analysis of the resected intestine revealed fibrin thrombi in both mesenteric arteries and veins. Furthermore, a cluster of large, abnormal lymphoid cells bordering the intima of most branches of the mesenteric veins and small vessels was observed. Immunohistochemical analysis revealed that these abnormal cells were positive for CD20, leading to a diagnosis of intravascular large B-cell lymphoma (IVLBCL). The patient was successfully treated with standard R-CHOP chemotherapy; however, the lymphoma recurred in the central nervous system 18 months after the initial diagnosis, and the patient died. Simultaneous thrombosis of the mesenteric artery and vein is unusual as a clinical manifestation of IVLBCL. However, IVLBCL should be taken into consideration when ischemic disorders of unknown cause, accompanied by fever of unknown origin, are encountered.

The prognostic impact of absolute lymphocyte and monocyte counts at diagnosis of diffuse large B-cell lymphoma in the rituximab era.

BACKGROUND: A recent report showed that the combination of the absolute lymphocyte count (ALC) and the absolute monocyte count (AMC) at diagnosis gave a prognostic score in diffuse large B-cell lymphoma (DLBCL). However, this model requires validation in other patient cohorts. METHODS: We retrospectively evaluated the prognostic impact of the combination of the ALC and the AMC at diagnosis in a cohort of 299 DLBCL patients who were treated in the rituximab era at a single institution. RESULTS: In univariate analyses, an ALC ≤1.0 × 10(9)/l [4-year overall survival (OS) rate 47.0 vs. 79.4%; p < 0.001] and an AMC ≥0.63 × 10(9)/l (4-year OS rate 52.4 vs. 75.6%; p < 0.001) were associated with inferior OS, respectively. In multivariate analyses, an ALC ≤1.0 × 10(9)/l and an AMC ≥0.63 × 10(9)/l were significantly associated with inferior OS independently of the International Prognostic Index. Furthermore, the combination of ALC and AMC could identify patients with the dismal prognosis; the 4-year OS rates for patients with ALC ≤1.0 × 10(9)/l and AMC ≥0.63 × 10(9)/l were 18.8%. CONCLUSIONS: The combination of ALC and AMC at diagnosis may be useful for the prognostic stratification of patients with DLBCL.

Successful treatment of γ-heavy-chain disease with rituximab and fludarabine.

An 84-year-old Japanese man was admitted because of pancytopenia. The bone marrow was hypoplastic with a predominance of abnormal small lymphocytes and grape cells, which were positive for CD19 and CD20, and partially for the surface ĸ-light chain. Systemic CT scanning showed neither lymph node swelling nor hepatosplenomegaly. Serum immunoelectrophoresis and rocket immunoselection assays showed the presence of monoclonal IgG protein without a corresponding light chain and faint IgMĸ monoclonal protein. Histologic analysis of the clot preparation of the bone marrow aspirate facilitated a diagnosis of lymphoplasmacytic lymphoma (LPL). PCR analysis of the marrow cells demonstrated a clonal rearrangement of the immunoglobulin heavy-chain gene. From these results, we made a final diagnosis of γ-heavy-chain disease (γ-HCD) with underlying LPL localized in the bone marrow. We performed only a single course of immunochemotherapy (rituximab and fludarabine) in view of severely impaired hematopoiesis, which resulted in marked reduction of lymphoma cells and improvement of hematopoiesis. This report suggests the efficacy of rituximab plus fludarabine therapy for LPL-associated γ-HCD.

[Fatal hepatic failure due to AL amyloidosis in a patient with multiple myeloma].

Although about 10 to 15% of patients with multiple myeloma (MM) develop AL amyloidosis, liver-restricted fatal amyloidosis is rare. We encountered such an MM patient. A 73-year-old female without a history of carpal tunnel syndrome was diagnosed with IgG-κ MM (Stage I by Durie & Salmon) in January, 2005. Because MM was exacerbated to Stage III in May, 2007, VAD (vincristine, adriamycin, dexamethasone) chemotherapy was performed with minor response, despite 3 courses of this regimen. Three courses of salvage chemotherapy (cyclophosphamide+melphalan; CM) were then performed with near partial response. In March, 2008, just before the 4th cycle of CM chemotherapy, she was slightly icteric with elevated biliary tract enzymes; therefore, treatment was switched to oral cyclophosphamide and prednisolone. At this time, she did not have macroglossia, skin eruption, gastrointestinal dysfunction, or bleeding. Echocardiography was also non-specific. One month later, she developed a marked bleeding tendency and leg edema. Laboratory tests showed a severe deterioration in liver function. In the middle of May, 2008, she progressed to hepatic coma and died of intracranial hemorrhage several days later. Autopsy showed that the liver was almost substituted by AL amyloid substance.

Milk casein-derived tripeptides, VPP and IPP induced NO production in cultured endothelial cells and endothelium-dependent relaxation of isolated aortic rings.

Milk casein-derived tripeptides, valyl prolyl proline (VPP), and isoleucyl prolyl proline (IPP) inhibit angiotensin-converting enzyme (ACE) and both fermented milk and proteolytic hydrolysates of milk casein containing these peptides exert blood pressure-lowering effects in animals and humans. On the top of these results, we have recently reported that the hydrolysate of milk casein containing both VPP and IPP improved the vascular endothelial function of subjects with stage I hypertension, enforcing us to elucidate the mechanism of the improvement of endothelial dysfunction by these peptides. For this purpose, we examined the effect of VPP and IPP on induction of nitric oxide (NO) production using cultured vascular endothelial cells and isolated arterial vessels. When both VPP and IPP were added to the medium of cultured endothelial cells at final concentrations of more than 100 nmol/l, the NO(x) (NO(2) and NO(3)) concentration in the medium was significantly higher than that of the control. Moreover, both VPP and IPP induced endothelium-dependent relaxation of isolated aortic rings, and these effects were inhibited by NO synthase inhibitors, K channel inhibitors, and bradykinin B2 receptor antagonists. These lines of results suggested that both VPP and IPP induced production of vasodilative substances including NO.

[Exacerbation of autoimmune neutropenia to agranulocytosis in association with severe autoimmune thrombocytopenia and hemolytic anemia in a patient with Sjögren's syndrome].

A 73-year-old woman with Sjögren's syndrome and autoimmune neutropenia (AIN) associated with large granular lymphocytosis of the polyclonal T cell type, demonstrated autoimmune thrombocytopenia (AIT) at diagnosis of sigmoid colon cancer. Ten months later, both AIN and AIT had exacerbated to agranulocytosis and severe thrombocytopenia below 10×10(9)/L, respectively. There were no dysplastic features of bone marrow hematopoietic cells. Furthermore, an in vitro assay of hematopoietic progenitors showed normal granuloid and erythroid colony formation. Although we serially treated her with prednisolone (oral), filgrastim, intravenous high-dose immunoglobulin infusion, cyclophosphamide (oral), danazol, cyclosporine A (oral), and rituximab, number of neutrophils and platelets elevated only temporarily. During the course of agranulocytosis and severe thrombocytopenia, the patient also developed autoimmune hemolytic anemia (AIHA). She died of pneumonia 5 months after the onset of agranulocytosis. This case is very unique and novel in terms of autoimmune phenomena simultaneously directed to granulocytes, platelets, and red blood cells under the background of Sjögren's syndrome.

Clinical Diagnosis of Toxoplasmosis via Histopathological and Antibody Examination of Five Immunocompetent Patients at Kobe City Medical Center General Hospital, 2008 to 2015.

Congenital toxoplasmosis, commonly known as TORCH, is a well-known syndrome, but even experienced obstetricians rarely encounter it. In Japan, there is good overall hygiene and raw or wild game meats are not eaten; therefore, the prevalence of Toxoplasma gondii infection and the antibody positivity rates have been low. This low prevalence rate also relates to the fact that Toxoplasma gondii infections are rarely observed in immunocompetent hosts. Exploration of the cases in which pathological examinations were performed at our hospital (Kobe City Medical Center General Hospital) revealed that acquired Toxoplasma infections were apparent in five immunocompetent patients over an 8-year period. The number of infections was unexpectedly high. The number of 5 cases was the highest in literature review to the extent that we could know. To prevent congenital toxoplasmosis, which manifests as intracranial calcifications, hydrocephalus, and chorioretinitis in severe cases, pregnant women and their doctors require proper knowledge about the risk factors and danger of this infection. We believe that from the viewpoint of cost performance relationship, it is appropriate to bear the test fee of about 50 USD for Toxoplasma IgG and IgM check for the test of congenital toxoplasmosis, if patients desired.

Successful living donor liver transplantation for severe hepatic GVHD histologically resembling autoimmune hepatitis after bone marrow transplantation from the same sibling donor.

A 30-year-old woman developed severe liver dysfunction 1 year after bone marrow transplantation (BMT) from an HLA-identical sibling donor for B lymphoblastic leukemia (B-ALL) during the tapering of cyclosporin A. The histologic picture resembled autoimmune hepatitis (AIH), although neither autoantibody nor hypergammaglobulinemia was detected. She entered hepatic coma, and underwent living donor liver transplantation from the same donor on day 421 after BMT. She is well 18 months after the procedure, showing normal liver function and hematopoiesis. AIH-like hepatic graft-versus-host disease (GVHD) has not been documented. This patient is the second case of living donor liver transplantation for hepatic GVHD from the same donor.

Hepatosplenic alphabeta T cell lymphoma.

A 32-year-old male with chronic hepatitis B was admitted to a hospital with cellulitis in the right leg in September 2006. Pancytopenia, hepatosplenomegaly, and systemic superficial lymph node swelling were noted, and he was referred to our hospital. He developed fever and liver dysfunction in June 2007 and underwent a splenectomy. His pancytopenia subsequently improved. A pathologic diagnosis of hepatosplenic alphabeta T cell lymphoma was made by examining spleen tissue and biopsy specimens of the liver and mesenteric lymph node. He had stage IVB disease because neoplastic T cells were noted in the bone marrow. The response of the lymphoma to conventional chemotherapy including the CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) and DeVIC (dexamethasone, etoposide, ifoshamide, carboplatin) regimens was poor and transient. A partial remission was obtained with an ESHAP (etoposide, cisplatin, cytarabine, methylprednisolone) regimen. Therefore, we planned a bone marrow transplantation (BMT) from an HLA-haploidentical sibling donor. He was moved to the Department of Hematology, Hyogo Medical College, to receive this BMT as part of a clinical trial. During the conditioning procedure for the transplantation, however, he died of septicemia. Since hepatosplenic alphabeta T cell lymphoma is very rare with only 23 reported cases to date, herein we report this case and discuss the therapeutic strategy.

[Graft-versus-leukemia effect by lymphocytes from the first donor after second cord blood transplantation in a patient with T-lymphoblastic lymphoma].

A 19-year-old girl with T-lymphoblastic lymphoma (T-LBL) was referred to our hospital because of refractory disease. After complete remission was achieved by the JALSG ALL-97 protocol, she received a bone marrow transplantation (BMT) from an unrelated, HLA-matched donor with myeloablative conditioning. Four months after BMT, T-LBL relapsed and donor lymphocyte infusion was ineffective. After partial remission was achieved with l-asparaginase therapy, she received 2 antigen-mismatched cord blood transplantation with non-myeloablative conditioning; however, sustained engraftment of cord blood stem cells has failed. This was associated with the reappearance of the blood cells from the first donor and the disappearance of leukemic cells from both the peripheral blood and bone marrow. Computed tomography showed no enlarged lymph nodes. The patient and the cord blood donor shared two minor histocompatibility antigens (mHAgs), while these mHAgs were not detected in the blood cells of the first donor. TCR analysis disclosed expanded oligoclonal Vbeta2T cells in the peripheral blood at relapse, and these cells secreted IFN-gamma in response to stimulation by the patient's leukemic cells. Moreover, these cells exhibited cytotoxicity against both leukemic cells and cord blood mononuclear cells. These results strongly suggest that Vbeta2T cells, derived from the first donor, may have been cytotoxic lymphocytes against both leukemic cells and cord blood stem cells.

[Therapeutic efficacy of cyclosporin A for refractory angioimmunoblastic T cell lymphoma].

The prognosis of angioimmunoblastic T cell lymphoma (AITL) is poor because of chemotherapy-resistance and the short duration of remission. In recent years, cyclosporin A (CyA) has been employed as a alternative treatment for AITL in some patients with the rationale that CyA inhibits the activity and proliferation of neoplastic T cells. We herein report 4 chemotherapy-resistant AITL patients who were treated with oral CyA. The dosage of CyA was individually determined in each patient in order to achieve a blood CyA concentration of around 200 ng/ml at the trough level. A patient in whom AITL had relapsed 3 months after high dose chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) achieved a sustained complete remission (CR) with CyA and underwent allogeneic HSCT. In 2 patients who had failed to respond to conventional chemotherapies, the circulating lymphoma cells rapidly disappeared after the initiation of CyA, and one of these patients demonstrated a durable CR. The other patient showed a good response to CyA, but the agent was discontinued because of infection. The remaining one patient with advanced AITL did not respond to CyA and died of disease progression. To our knowledge, the efficacy of CyA for chemotherapy-resistant AITL, even in a leukemic state, has not previously been reported.

[Angioimmunoblastic T-cell lymphoma complicated by recurrent drug-induced agranulocytosis].

A 73-year-old man was hospitalized with fever, erythema, generalized superficial lymphadenopathy and marked neutropenia in July 2007. Hematologic examination demonstrated a white blood cell count of 1,400/microl with 0% neutrophils, and 18% abnormal lymphocytes. A bone marrow aspirate showed marked myeloid hypoplasia. A diagnosis of drug-induced agranulocytosis was made. Although neutrophil counts immediately returned to normal levels in response to filgrastim, fever, skin rash and systemic lymphadenopathy were all persistent. He also developed autoimmune hemolytic anemia and a second episode of agranulocytosis. The causative agent of the both episodes of agranulocytosis appeared to be acetaminophen. The histologic picture of a biopsied lymph node showed diffuse infiltration of polymorphous lymphoid cells with clear cytoplasm and proliferation of arborizing capillary vessels. Based on the histologic findings, PCR, and immunohistologic analyses, he was diagnosed with angioimmunoblastic T cell lymphoma (AILT) in leukemic state. The response of the lymphoma to conventional chemotherapy (CHOP and ESHAP) was poor. We next performed an immunomodulatory therapy using cyclosporine A to suppress cytokine production by neoplastic T cells. The treatment resulted in a partial remission of AILT including disappearance of circulating lymphoma cells. To our knowledge, this is the first published report of AILT complicated by drug-induced agranulocytosis.