tacrolimus and Hodgkin-Disease

The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus have been used widely as corticosteroid-sparing agents in treating various cutaneous diseases. However, the association between TCIs and risk of malignancy remains controversial. By systematic review and meta-analysis, we aimed to investigate the association between TCIs and lymphoma. Eligible studies in online databases were identified from the date of inception to August 30, 2020. To assess the outcome of TCI-related risk of lymphoma, analysis of cohort studies comparing the incidence of lymphoma with and without treatment with TCIs was performed. Furthermore, the subgroup analyses of Hodgkin lymphoma and non-Hodgkin lymphoma were also conducted. The pooled results revealed that using topical tacrolimus (RR 1.68, 95 % CI 1.39-2.04) or pimecrolimus (RR 1.40, 95 % CI 1.13-1.74) significantly increased the risk of lymphoma. TCI users also showed higher incidence of lymphoma in the range of 0.02-0.09 %, compared to that of 0.02-0.06 % in the control group. Additionally, subgroup analyses showed both tacrolimus (RR 1.89; 95 % CI 1.53-2.32) and pimecrolimus (RR 1.38; 95 % CI 1.09-1.74) had significantly higher risk of non-Hodgkin lymphoma, but no increased risk of Hodgkin lymphoma. In conclusion, TCI-exposed patients have a significantly increased risk of lymphoma, especially non-Hodgkin lymphoma.

Topics: Administration, Topical; Calcineurin Inhibitors; Dermatitis, Atopic; Hodgkin Disease; Humans; Lymphoma; Tacrolimus

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

Patients who undergo allogeneic stem cell transplantation and subsequent radiation therapy uncommonly develop graft-versus-host disease within the irradiated area. We quantified the incidence of this complication, which is a novel contribution to the field. From 2010 to 2014, 1849 patients underwent allogeneic stem cell transplantation, and 41 (2 %) received radiation therapy afterward. Of these, two patients (5 %) developed graft-versus-host disease within the irradiated tissues during or immediately after radiation therapy.. The first patient is a 37-year-old white man who had Hodgkin lymphoma; he underwent allogeneic stem cell transplantation from a matched unrelated donor and received radiation therapy for an abdominal and pelvic nodal recurrence. After 28.8 Gy, he developed grade 4 gastrointestinal graft-versus-host disease, refractory to tacrolimus and steroids, but responsive to pentostatin and photopheresis. The other patient is a 24-year-old white man who had acute leukemia; he underwent allogeneic stem cell transplantation from a matched related donor and received craniospinal irradiation for a central nervous system relapse. After 24 cobalt Gy equivalent, he developed severe cutaneous graft-versus-host disease, sharply delineated within the radiation therapy field, which was responsive to tacrolimus and methylprednisolone.. We conclude that graft-versus-host disease within irradiated tissues is an uncommon but potentially serious complication that may follow radiation therapy in patients who have undergone allogeneic stem cell transplantation. Clinicians must be aware of this complication and prepared with strategies to mitigate risk. Patients who have undergone allogeneic stem cell transplantation represent a unique population that may offer novel insight into the pathways involved in radiation-related inflammation.

Topics: Adult; Anti-Inflammatory Agents; Antineoplastic Agents; Fatal Outcome; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Immunosuppressive Agents; Leukemia, Biphenotypic, Acute; Male; Methylprednisolone; Pentostatin; Photopheresis; Radiotherapy, Adjuvant; Tacrolimus; Transplantation, Homologous; Young Adult

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Doxorubicin; Glomerulonephritis, Membranous; Hodgkin Disease; Humans; Immunosuppressive Agents; Male; Middle Aged; Nephrotic Syndrome; Prednisone; Remission Induction; Tacrolimus; Time Factors; Vinblastine

Topics: Administration, Oral; Alleles; Antifungal Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Capsules; Combined Modality Therapy; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Dacarbazine; Doxorubicin; Drug Interactions; Drug Therapy, Combination; Female; Genotype; Graft vs Host Disease; Half-Life; Hodgkin Disease; Humans; Immunosuppressive Agents; Infusions, Intravenous; Intestines; Itraconazole; Methotrexate; Tacrolimus; Transplantation, Homologous; Vinblastine; Young Adult

A 46-year-old woman with Hodgkin's disease who underwent nonmyeloablative allogeneic stem cell transplantation developed cortical blindness, seizures, and left hemiparesis on day 100 while receiving tacrolimus (FK506) and prednisone for the treatment of graft-versus-host disease (GVHD). Magnetic resonance imaging revealed multiple changes, mainly in the bilateral occipital lobes, suggesting FK506-related leukoencephalopathy. These abnormalities improved after discontinuation of FK506. However, 3 days after the episode, cerebral hemorrhage in the left occipital lobe with perforation to the left subdural space occurred. Although FK506-induced leukoencephalopathy with cerebral hemorrhage is considered the more severe form of such leukoencephalopathy, the patient's neurological symptoms almost completely resolved and radiographic findings improved after discontinuation of FK506, tapering of methylprednisolone, and initiation of mycophenolate mofetil. FK506-related leukoencephalopathy is a rare complication after allogeneic stem cell transplantation. Although the symptoms usually subside after discontinuation of FK506, therapeutic intervention in many cases may result in severe complications, including GVHD and vascular disease. We consider it important to use immunosuppressive agents without vascular endothelial toxicity for preventing the development of fatal GVHD after discontinuation of FK506.

Topics: Cerebral Hemorrhage; Disease-Free Survival; Female; Graft vs Host Disease; Hodgkin Disease; Humans; Leukoencephalopathy, Progressive Multifocal; Middle Aged; Peripheral Blood Stem Cell Transplantation; Remission Induction; Tacrolimus; Transplantation Conditioning

Topics: Adult; Bone Transplantation; Brain; Brain Edema; Cyclosporine; Hodgkin Disease; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Syndrome; Tacrolimus