Tocilizumab for severe cytokine-release syndrome after haploidentical donor transplantation in a patient with refractory Epstein-Barr virus-positive diffuse large B-cell lymphoma.

It has been well documented that patients may develop cytokine-release syndrome (CRS) following the administration of monoclonal antibodies, such as chimeric antigen receptor-modified T cell. Cytokine-release syndrome is a common complication in patients who have received haploidentical donor allogeneic haematopoietic cell transplantation (haplo-HCT). Although severe CRS after haplo-HCT is a potentially life-threatening toxicity, a standard treatment has not been established. Cytokine blockade with tocilizumab, an anti-IL-6 receptor antibody, has been effective for the treatment of patients with CRS after chimeric antigen receptor-modified T-cell treatment and has also improved CRS after haplo-HCT. A 46-year-old man was diagnosed with haemophagocytic syndrome associated with Epstein-Barr virus-positive diffuse large B-cell lymphoma. Salvage chemotherapy was unsuccessful; consequently, he received haplo-HCT. On day +4, he developed grade 3 CRS, subsequently high-dose corticosteroid initiated. Nevertheless, on day +6, he developed grade 4 CRS, resulting in requirement for ventilator support and multiple vasopressors. Corticosteroid could not improve severe CRS; therefore, tocilizumab was administered on day +14. Serum C-reactive protein level transiently decreased and weaned multiple vasopressors. Although CRS improved, he developed candidaemia; consequently, he died on day +34. Tocilizumab could transiently improve severe CRS after haplo-HCT. Although tocilizumab may have led to the improvement of CRS, a remaining concern is whether it inhibited the patient's ability to mount antifungal immunity, leading to their demise.

Three coexisting lymphomas in a single patient: composite lymphoma derived from a common germinal center B-cell precursor and unrelated discordant lymphoma.

Composite lymphoma (CL) is a rare disorder defined as the coexistence of two or more distinct lymphoma subtypes at a single anatomic site. Discordant lymphoma (DL), which is the simultaneous occurrence of two or more distinct lymphoma subtypes at different sites, is also rare. CL complicated with DL involving three distinct subtypes of lymphoma in the same patient is an extremely rare disease. Clonal relationships in CL and DL are commonly investigated by molecular analysis using mutational status with t(14;18)BCL2/IgH translocation and immunoglobulin heavy chain variable-region (IgVH) gene rearrangement. A 73-year-old woman was admitted to our hospital with systemic lymphadenopathy and was initially diagnosed with diffuse large B-cell lymphoma based on pathological features of the biopsied esophageal tumor. However, the results of inguinal lymph node biopsy led to a revised pathological diagnosis CL consisting of Hodgkin lymphoma and follicular lymphoma. Three distinct coexisting lymphomas were identified in this individual patient. Molecular analysis revealed CL derived from common germinal center B-cell precursors, while clonal relationship between CL and DL was not clarified. This case suggests a mechanism underlying B-cell lymphoma pathogenesis involving two pivotal somatic mutations, t(14;18)BCL2/IgH translocation and IgVH rearrangement.

5q- syndrome-like features as the first manifestation of myelodysplastic syndrome in a patient with an unbalanced whole-arm translocation der(5;19)(p10;q10).

Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before. Bone marrow aspirate (BM) revealed low blast counts with trilineage dysplastic cells, and fluorescent in situ hybridization revealed the loss of colony-stimulating factor 1 receptor (CSF1R) signals at 5q33-34. Although the initial manifestation was 5q- syndrome, G-banded metaphase analysis and spectral karyotyping analysis revealed der(5;19)(p10;q10). Consequently, a diagnosis of therapy-related MDS (t-MDS) was made. She failed to respond to azacitidine and lenalidomide therapy. Consequently, transfusion-dependent anemia and thrombocytopenia developed with increasing myeloblasts. Cytarabine, aclarubicin, and granulocyte colony-stimulating factor therapy also failed, and unfortunately the patient died. Thus, MDS with der(5;19)(p10;q10) may represent a platinum agent-related t-MDS that is highly resistant to chemotherapy.

Subdural Hematoma Associated with Dasatinib and Intrathecal Methotrexate Treatment in Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia.

Dasatinib has been associated with an increased risk of bleeding, with the most prominent risk noted in patients with advanced-stage chronic myeloid leukemia and thrombocytopenia. We herein report two cases of Philadelphia chromosome-positive acute lymphoblastic leukemia in which a subdural hematoma developed in association with low-dose (40-50 mg/day) dasatinib treatment and lumbar puncture for intrathecal methotrexate injection. Both patients were in complete remission, with normal platelet counts and coagulation status. We suggest that dasatinib, even at a low dose, may impair platelet aggregation and that lumbar puncture may increase the risk of a subdural hematoma (occasionally bilateral) in patients receiving dasatinib.

Rituximab-induced Acute Thrombocytopenia in High Tumor Burden Follicular Lymphoma.

Rituximab-induced acute thrombocytopenia (RIAT), a rare complication of rituximab administration, has not yet been described in follicular lymphoma (FL). A 65-year-old man received rituximab for the treatment of high tumor burden follicular lymphoma in the leukemic phase. The next day, his platelet count abruptly dropped from 85,000 to 5,000/µL, which spontaneously recovered in a few days without specific treatment. We speculate that the occurrence of infusion-related cytokine release syndrome in rituximab-sensitive high tumor burden FL contributed to the development of RIAT. Frequent monitoring of the platelet count is advisable for select patients considered to be at a high risk for RIAT.