tacrolimus and Lymphoma--Large-B-Cell--Diffuse

The heart transplantation is the most important treatment for patients with end-stage severe heart disease who failed to conventional therapy. Post-transplant lymphoproliferative disorder is the second most common malignancy in heart transplant recipients. However, primary central nervous system lymphoma (PCNSL) after heart transplantation is an extremely rare condition.. This report described a 53-year-old male who was diagnosed as PCNSL 17 months after heart transplantation.. The patient was admitted to the local hospital presenting with dizziness, headache, and reduced left-sided power and sensation for 1 week. He had a medical history of heart transplantation because of the dilated cardiomyopathy 17 months ago and had a 17-month history of immunosuppressive therapy with tacrolimus. A computed tomography scan of the brain revealed a bulky mass in the right temporal lobe. The emergency intracranial mass resection and cerebral decompression were performed in our hospital. The histopathology of the brain lesions showed diffuse large B-cell lymphoma. A further FDG positron emission tomography-computed tomography scan of the whole body showed no significantly increased metabolic activity in other regions. The final diagnosis of this patient was PCNSL after heart transplantation.. Given the poor health condition, with the patient's consent, the whole brain radiotherapy was performed with supportive care.. The disease deteriorated rapidly during the period of receiving radiotherapy, and he died within 2 months from the diagnosis.. PCNSL after heart transplantation is an extremely rare phenomenon with extremely poor prognosis. We should pay close attention to the heart recipients, especially when the patients present with neurological symptoms and signs. The available treatment options for PCNS-post-transplant lymphoproliferative disorder include the reduction of immunosuppressive drugs, immune-chemotherapy, operation, radiotherapy. However, individual treatments for heart transplant recipients with PCNSL should be based on the performance status and tolerance to treatment, combined with the doctor's experience and supportive care.

Topics: Brain Neoplasms; Heart Transplantation; Humans; Immunosuppressive Agents; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Tacrolimus; Tomography, X-Ray Computed

A 69-year-old woman, who had been diagnosed as having Sjögren's syndrome at 37 years old and mixed connective tissue disease at 42 years old, was under treatment with oral prednisolone. In 2009, she was diagnosed as having active systemic lupus erythematosus, and started on treatment with tacrolimus at 3 mg/day. In 2010, para-aortic lymphadenopathy and superficial multiple lymphadenopathy were detected. Tacrolimus was discontinued. Axillary lymph node biopsy revealed Epstein-Barr (EB) virus-negative CD5-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified into clinical stage IIIA and as being at high risk according to the international prognostic index. After the discontinuation of tacrolimus, the lymph nodes reduced temporarily in size. In January 2011, the lymphadenopathy increased again, and the patient received a total of 8 courses of therapy with rituximab, pirarubicin, vincristine, cyclophosphamide and prednisolone, followed by intrathecal injection to prevent central nervous system infiltration, which was followed by complete remission. In February 2012, fluorodeoxyglucose positron emission tomography showed relapse in multiple lymph nodes and central nervous system infiltration. The patient was considered to have iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the WHO, and this is the first reported case of CD5-positive DLBCL and central nervous system infiltration following administration of the drug. The patient was considered to have a poor prognosis as EB virus was negative, discontinuation of tacrolimus was ineffective and there was evidence of central nervous system infiltration.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; CD5 Antigens; Cyclophosphamide; Doxorubicin; Female; Herpesvirus 4, Human; Humans; Iatrogenic Disease; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphoma, Large B-Cell, Diffuse; Mixed Connective Tissue Disease; Prednisolone; Rituximab; Sjogren's Syndrome; Tacrolimus; Vincristine

We report a case of donor-derived diffuse large B-cell lymphoma (DLBCL), which developed 5 years after stem cell transplantation from a human leukocyte antigen (HLA)-haploidentical donor for acute myeloid leukemia (AML). A 51-year-old male was diagnosed with AML with variant KMT2A translocation involving t(6;11)(q13;q23). After 12 cycles of azacitidine treatment, fluorescence in situ hybridization (FISH) for KMT2A split signal indicated that 94% of his bone marrow (BM) cells were positive. He underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-haploidentical son. The preconditioning regimen consisted of fludarabine, busulfan, melphalan, and antithymocyte globulin (ATG). The graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and short-term methotrexate. On day 28, KMT2A FISH analysis indicated that he had achieved a complete response (CR). He continued to receive tacrolimus for the limited type of cutaneous chronic GVHD. Five years after the transplantation, positron emission tomography/computed tomography (PET/CT) showed an abdominal tumor. The tumor was diagnosed as DLBCL without Epstein-Barr virus. BM aspiration revealed the infiltration of lymphoma cells with t(8;14)(q24;q32). Chimerism analysis showed that both the peripheral blood (PB) and abdominal lymphoma cells were of donor origin. After 4 cycles of salvage chemotherapy, PET/CT showed that a CR had been achieved. He underwent a second PBSCT from an HLA-identical unrelated donor. The preconditioning regimen and GVHD prophylaxis were the same as those for the first PBSCT without ATG. The patient's PB revealed complete second donor-type chimerism, and the patient has maintained a CR since the second transplantation.

Topics: Antilymphocyte Serum; Azacitidine; Busulfan; Epstein-Barr Virus Infections; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpesvirus 4, Human; HLA Antigens; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Methotrexate; Middle Aged; Positron Emission Tomography Computed Tomography; Tacrolimus; Transplantation Conditioning

Topics: Female; Humans; Ileal Neoplasms; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Lymphoma, Large B-Cell, Diffuse; Tacrolimus; Tomography, X-Ray Computed; Young Adult

Other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs) occur in patients receiving immunosuppressive drugs for autoimmune diseases; however, their clinicopathological and genetic features remain unknown. In the present study, we analysed 67 patients with OIIA-LPDs, including 36 with diffuse large B-cell lymphoma (DLBCL)-type and 19 with Hodgkin lymphoma (HL)-type. After discontinuation of immunosuppressive drugs, regression without relapse was achieved in 22 of 58 patients. Spontaneous regression was associated with Epstein-Barr virus positivity in DLBCL-type (P = 0·013). The 2-year overall survival and progression-free survival (PFS) at a median follow-up of 32·4 months were 92·7% and 72·1% respectively. Furthermore, a significant difference in the 2-year PFS was seen between patients with DLBCL-type and HL-type OIIA-LPDs (81·0% vs. 40·9% respectively, P = 0·021). In targeted sequencing of 47 genes in tumour-derived DNA from 20 DLBCL-type OIIA-LPD samples, histone-lysine N-methyltransferase 2D (KMT2D; eight, 40%) and tumour necrosis factor receptor superfamily member 14 (TNFRSF14; six, 30%) were the most frequently mutated genes. TNF alpha-induced protein 3 (TNFAIP3) mutations were present in four patients (20%) with DLBCL-type OIIA-LPD. Cases with DLBCL-type OIIA-LPD harbouring TNFAIP3 mutations had shorter PFS and required early initiation of first chemotherapy. There were no significant factors for spontaneous regression or response rates according to the presence of mutations. Overall, OIIA-LPDs, especially DLBCL-types, showed favourable prognoses.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Histone-Lysine N-Methyltransferase; Hodgkin Disease; Humans; Iatrogenic Disease; Immunologic Deficiency Syndromes; Immunosuppressive Agents; Kaplan-Meier Estimate; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Myeloid-Lymphoid Leukemia Protein; Prognosis; Progression-Free Survival; Proportional Hazards Models; Receptors, Tumor Necrosis Factor, Member 14; Retrospective Studies; Rheumatic Diseases; Tacrolimus; Tumor Necrosis Factor alpha-Induced Protein 3

A 76-year-old woman with dermatomyositis was being treated with prednisolone, tacrolimus, and mycophenolate mofetil. There was a solitary lung nodule in the right middle lobe on chest computed tomography at a routine follow-up examination. A transbronchial lung biopsy was performed, and the histopathologic findings indicated diffuse large B-cell lymphoma. An immunodeficiency-associated lymphoproliferative disorder was suspected, and mycophenolate mofetil was stopped without adding any other therapy. Nine months later, the pulmonary nodule had disappeared on chest computed tomography.

Topics: Aged; Female; Humans; Lung; Lymphoma, Large B-Cell, Diffuse; Mycophenolic Acid; Solitary Pulmonary Nodule; Tacrolimus

A 49-year-old man was admitted to our hospital with pancreatitis. He was diagnosed with systemic lupus erythematosus at 34 years of age and was being treated with oral tacrolimus (3 mg/day) and predonine (10 mg/day) for the past 15 months. The computed tomography (CT) scan showed the mass lesion had invaded the pancreatic head via thickening of the duodenal wall. Upper gastrointestinal endoscopy showed the all-round ulcerative lesion from the superior duodenal angle to the descending portion. Histological examination confirmed the diagnosis of diffuse large B cell lymphoma (DLBCL). Tacrolimus therapy was stopped due to the possibility of immunodeficiency-related lymphoproliferative disease; however, the lesion did not improve. Consequently, he was administered rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). After six courses of R-CHOP therapy, a partial response was confirmed on CT. One month after the completion of chemotherapy, a gastrojejunal anastomosis was performed because of duodenal stenosis. He has since been well without recurrence. It was difficult to identify the risk factor for DLBCL; therefore, both the disease activity and immunosuppressive therapy should be taken into consideration as carrying a risk. In the present case, the symptom of pancreatitis enabled an early diagnosis of DLBCL.

Topics: Acute Disease; Anti-Inflammatory Agents; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Duodenal Neoplasms; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Pancreatitis; Prednisolone; Prednisone; Rituximab; Tacrolimus; Vincristine

Topics: Azathioprine; Female; Humans; Immunosuppression Therapy; Liver Transplantation; Lymphoma, Large B-Cell, Diffuse; Sirolimus; Steroids; Tacrolimus; Young Adult

Topics: Antilymphocyte Serum; Brain Neoplasms; Cytomegalovirus Retinitis; Epstein-Barr Virus Infections; Female; Ganciclovir; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Neoplasms; Kidney Transplantation; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Postoperative Complications; Prednisolone; Radiography; RNA, Viral; Tacrolimus; Transplantation, Homologous