ABSTRACT
Background: Various glomerular pathologies have been reported in patients who have undergone haematopoietic stem cell transplantation (HSCT), but the data on clinico-pathological correlations and clinical outcome remain limited. Methods: We analysed the clinical and histopathological data of patients who had biopsy-proven de novo glomerular diseases after HSCT since 1999. Results: A total of 2204 patients underwent HSCT during the period 1999-2021, and 31 patients (1.4%) developed de novo glomerular diseases after a mean duration of 2.8 ± 2.7 years after HSCT. Fifteen of these patients (48.4%) had graft-versus-host-disease prior to or concomitant with renal abnormalities. Proteinuria and eGFR at the time of kidney biopsy were 4.1 ± 5.3 g/day and 50.8 ± 25.4 mL/min/1.73 m2, respectively. Kidney histopathologic diagnoses included thrombotic microangiopathy (TMA) (38.7%), membranous nephropathy (MN) (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). Immunosuppressive treatment was given to patients who presented with nephrotic-range proteinuria and/or acute kidney injury, while renin-angiotensin-aldosterone blockade was given to all patients with proteinuria ≥1 g/day, with complete and partial response rates of 54.8% and 19.4%, respectively. One patient with TMA progressed to end-stage kidney disease after 24 weeks, and two patients, one with TMA and one with MN, (6.4%) progressed to chronic kidney disease (CKD) Stage ≥3. Kidney and patient survival rates were 96.6% and 83.5%, respectively, at 5 years. Conclusion: De novo glomerular diseases with diverse histopathologic manifestations affect 1.4% of patients after HSCT, and approximately 10% develop progressive CKD.
ABSTRACT
OBJECTIVES: Bendamustine is a standard treatment for low-grade B-cell lymphomas, and considered safe in clinical trials. Its safety in routine practice might be different. METHODS: We retrospectively analyzed the infection complications in an unselected cohort of patients treated with bendamustine over a nine-year period. Patients were regularly monitored for blood counts and cytomegalovirus (CMV) reactivation by antigen assay and polymerase chain reaction. They received granulocyte colony stimulating factor for neutropenia, and routine anti-pneumocystis and optional anti-fungal prophylaxis. RESULTS: There were 179 men and 127 women at a median age of 61.5 (20-90) years, 52% receiving bendamustine for relapsed/refractory disease. Malignancies included low-grade B-cell lymphomas (54%), myeloma (10%), T-cell lymphomas (11%), Hodgkin lymphoma (2%) and other lymphoid neoplasms (23%). Most patients had good performance status (Eastern Cooperative Oncology Group score: 0-1, 72%). CMV reactivation occurred in 58 patients (19%) at a median age of 68 (39-85) years. Univariate analysis showed CMV reactivation to be significantly associated with elevated lactate dehydrogenase (P = 0.045), decreased albumin (P = 0.003) and older age (reactivation versus no reactivation: 66.3 ± 11.4 versus 59.4 ± 14.5 years, P = 0.0016). Age remained the only significant risk on multivariate analysis. CMV reactivation resulted in retinitis (N = 4), ependymitis/ventriculitis (N = 1) and duodenitis/colitis (N = 1). Invasive fungal disease occurred in five patients (candidemia, N = 2; aspergillosis N = 1; cryptococcemia, N = 1; scedosporiosis, N-1). Nineteen patients had culture positive septicaemia. CONCLUSION: Our observations showed that even with a vigorous anti-infective strategy, bendamustine treatment was still associated with significant risks of bacterial and opportunistic viral and fungal infections.
Subject(s)
Bacterial Infections , Cytomegalovirus Infections , Hematologic Neoplasms , Lymphoma, B-Cell , Aged , Aged, 80 and over , Bacterial Infections/complications , Bendamustine Hydrochloride/adverse effects , Cytomegalovirus Infections/etiology , Female , Hematologic Neoplasms/complications , Hematologic Neoplasms/drug therapy , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18-86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities.
Subject(s)
Anemia, Aplastic , Adolescent , Adult , Aged , Aged, 80 and over , Anemia, Aplastic/chemically induced , Anemia, Aplastic/drug therapy , Antilymphocyte Serum/therapeutic use , Benzoates/adverse effects , Cyclosporine/therapeutic use , Female , Humans , Hydrazines/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Pyrazoles , Treatment Outcome , Young AdultABSTRACT
Immunoglobulin G4-related disease (IgG4-RD) has rarely been associated with lymphoid neoplasms, the spectrum of which remains unclear. B-cell lymphoid neoplasms (LN) associated with IgG4-RD diagnosed in a 4-year period were analysed. There were five men and three women at a median age of 76.5 (52-90) years; three with synchronous IgG4-RD and LN; three with IgG4-RD preceding LN by 2, 3, and 22 years; and two with LN preceding IgG4-RD by 2.5 and 7 years. All patients presented with disseminated lymphadenopathy. Monoclonal gammopathy of undetermined significance (MGUS)/smouldering multiple myeloma (SMM) was found in three patients, all with an IgGκ paraprotein. Levels of IgGκ and IgG4 correlated. Diffuse large B-cell lymphoma (DLBCL) was found in three patients, with one case showing co-existing lymphoma and IgG4-RD in the same lymph node biopsy. The remaining two cases were marginal zone lymphoma (MZL) developing in a lacrimal gland previously involved by IgG4-RD; and nodular lymphocyte predominant Hodgkin lymphoma (NLP-HL) diagnosed in a lymph node with concomitant IgG4-RD. Low-dose continuous prednisolone was given for MGUS/SMM, with both monoclonal IgGκ and IgG4 responding. Combination chemotherapy was given for DLBCL, with two patients achieving complete response and one patient dying from refractory lymphoma. The patient with MZL refused treatment, whereas the case of NLP-HL responded completely to chemotherapy. Our findings together with previous observations suggest that IgG4-RD has an increased risk of B-cell neoplasms. Patients with IgG4-RD presenting with lymphadenopathy require vigorous investigations to exclude lymphoid neoplasms.
Subject(s)
Hodgkin Disease/complications , Immunoglobulin G4-Related Disease/complications , Lymphadenopathy/complications , Lymphoma, B-Cell, Marginal Zone/complications , Lymphoma, Large B-Cell, Diffuse/complications , Monoclonal Gammopathy of Undetermined Significance/complications , Aged , Aged, 80 and over , Disease Management , Female , Hodgkin Disease/therapy , Humans , Immunoglobulin G , Immunoglobulin G4-Related Disease/therapy , Lymphadenopathy/therapy , Lymphoma, B-Cell, Marginal Zone/therapy , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/therapyABSTRACT
Graft-versus-host disease (GVHD) is an important complication after allogeneic haematopoietic stem cell transplantation (HSCT). Corticosteroids are the standard first-line treatment. Steroid-resistant/-dependent (SR/D) acute and chronic GVHD (aGVHD, cGVHD) lead to significant morbidity/mortality. The JAK2 inhibitor ruxolitinib has recently been shown in clinical trials to be effective in SR/D aGVHD and cGVHD. We retrospectively analysed the efficacy and safety of ruxolitinib in a cohort of SR/D aGVHD and cGVHD patients treated in a non-trial setting. In the aGVHD cohort, there were 14 men and 12 women, median age at 38 (19-63) years. At day 28 post-ruxolitinib, the overall response rate (ORR) was 86% (complete response, CR, 36%; partial response, PR, 50%). Continued ruxolitinib beyond day 28 resulted in a final CR of 68%. However, 3/15 (20%) of CR patients developed cGVHD. In the cGVHD cohort, there were 16 men and 15 women, median age at 33 (21-64) years. The ORR, CR and PR rates changed with continued ruxolitinib treatment, being 86%, 17% and 69% at 1 month; 79%, 38% and 41% at 3 months; and 83%, 52% and 31% at 6 months. Five patients had overlap GVHD, four of whom achieved CR. Multivariate analysis showed that superior overall survival and failure-free survival were associated with CR at day 28 for aGVHD, and CR at 1 year for cGVHD. Ruxolitinib treatment was efficacious for SR/D aGVHD and cGVHD, and continued treatment for at least 6 months was needed to maximize benefit.
Subject(s)
Graft vs Host Disease/drug therapy , Nitriles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Acute Disease , Adult , Chronic Disease , Female , Graft vs Host Disease/epidemiology , Humans , Janus Kinase 2/antagonists & inhibitors , Male , Middle Aged , Retrospective Studies , Steroids/therapeutic use , Survival Analysis , Young AdultABSTRACT
The efficacy and safety of low-dose anti-PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1-6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto-HSCT]: 18%), the overall response rate (ORR) by positron emission tomography-computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%). Median cumulative dose for achieving best response was 400 (300-800) mg. Median progression-free survival (PFS) was 35 months. Median overall survival (OS) was not reached. Adverse events (AEs) of grade 1-2 were observed in three patients. In the nivolumab cohort (N = 6), who had failed a median of three (2-6) therapies (BV: 50%; auto-HSCT: 17%; allogeneic HSCT: 34%), the ORR was 100% (mCR: 67%; PR: 17%; indeterminate response: 17%). Median cumulative dose for achieving best response was 160 (160-360) mg. Median PFS was 33 months. Median OS was not reached. AEs of grade 1-2 were observed in four patients, two of whom had pre-existing autoimmune conditions. Five patients with Epstein-Barr virus (EBV) positive Reed-Sternberg cells underwent monitoring of plasma EBV DNA, which became negative in four mCR patients but remained positive in one PR patient who died ultimately from refractory lymphoma. Low-dose pembrolizumab and nivolumab were highly efficacious and safe in relapsed/refractory cHL. These observations have significant financial implications in resource-constrained settings.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Adult , Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Resistance, Neoplasm , Female , Hodgkin Disease/diagnosis , Hodgkin Disease/mortality , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local , Neoplasm Staging , Nivolumab/administration & dosage , Positron Emission Tomography Computed Tomography , Retreatment , Retrospective Studies , Survival Analysis , Treatment Outcome , Young AdultSubject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Brentuximab Vedotin/administration & dosage , Epstein-Barr Virus Infections , Herpesvirus 4, Human/metabolism , Lenalidomide/administration & dosage , Lymphoma, T-Cell , Neoplasms, Second Primary , Positron Emission Tomography Computed Tomography , Aged , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Epstein-Barr Virus Infections/diagnostic imaging , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/etiology , Epstein-Barr Virus Infections/metabolism , Etoposide/administration & dosage , Humans , Lymphoma, T-Cell/diagnostic imaging , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/metabolism , Male , Neoplasms, Second Primary/diagnostic imaging , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/metabolism , Neoplasms, Second Primary/virology , Prednisolone/administration & dosage , Vincristine/administration & dosageABSTRACT
Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18- to 65-year-old AML patients refractory to first-line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high-dose cytarabine consolidation, with clofarabine (30 mg/m2 /d, Days 1-5), cytarabine (750 mg/m2 /d, Days 1-5), and mitoxantrone (12 mg/m2 /d, Days 3-5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mutational profile of a 69-gene panel was evaluated. Twenty-six men and 26 women at a median age of 46 (22-65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty-two CR/CRi patients underwent allo-HSCT. The 2-year overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo-HSCT (P = .005), and superior RFS and EFS were associated with allo-HSCT (P < .001). Remarkably, CR after CLAM and allo-HSCT resulted in 2-year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment-related mortality and the performance of allo-HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/drug therapy , Adult , Aged , Chemotherapy-Induced Febrile Neutropenia/epidemiology , Clofarabine/administration & dosage , Cytarabine/administration & dosage , Disease-Free Survival , Female , Humans , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Mitoxantrone/administration & dosage , Neoplasm Recurrence, Local , Survival Rate , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Transplantation, Homologous , Young AdultSubject(s)
Brain Neoplasms/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Nivolumab/administration & dosage , Aged , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Humans , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Magnetic Resonance Imaging , MaleABSTRACT
BACKGROUND: Strategies using oral arsenic trioxide (As2 O3 ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases. METHODS: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m2 /d, oral As2 O3 at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m2 /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m2 /d × 2) and cytarabine (100 mg/m2 /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As2 O3 induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features. RESULTS: The oral As2 O3 induction cohort showed a complete remission (CR) rate of 100%. After a median of 37 months (range, 13-82 months), there were no relapses, so conventional risks (age, leukocyte and platelet counts, and Fms-like tyrosine kinase 3 [FLT3] mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) rates were 100% at 3 years and 94.1% at 5 years. The non-As2 O3 induction cohort showed a CR rate of 100%. After a median of 52 months (range, 14-77 months), there were 3 relapses (8%). Comparable patients in the oral As2 O3 induction and non-As2 O3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As2 O3 induction cohort. CONCLUSIONS: The incorporation of oral As2 O3 into induction for newly diagnosed APL was safe and decreased relapses.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Promyelocytic, Acute/drug therapy , Administration, Oral , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Arsenic Trioxide/administration & dosage , Female , Humans , Leukemia, Promyelocytic, Acute/mortality , Male , Middle Aged , Prospective Studies , Treatment Outcome , Tretinoin/administration & dosage , Young AdultABSTRACT
BACKGROUND: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined. METHODS: The role of an oral arsenic trioxide (As2 O3 )-based regimen in the management of patients who had APL in CR2 was examined. RESULTS: Seventy-three patients with APL in first relapse (R1) were studied. Oral As2 O3 -based reinduction resulted uniformly in CR2, irrespective of previous As2 O3 exposure. All patients received oral As2 O3 -based maintenance in CR2. At a median follow-up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and 49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans retinoic acid, oral As2 O3 , and ascorbic acid. Reinduction and maintenance treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35 patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had self-limiting QTc prolongation. The 10-year leukemia-free survival rate was 56.8%. Thirty patients developed R2. Oral As2 O3 -based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As2 O3 maintenance. At a post-CR3 follow-up of 30 months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10-year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively. Prior receipt of oral As2 O3 maintenance in CR1 was the only risk factor for inferior leukemia-free survival. Central nervous system involvement occurred in 15 patients, including 5 who remained alive. Relapse during oral As2 O3 therapy was the only significant risk factor for central nervous system involvement. CONCLUSIONS: For patients with relapsed APL, As2 O3 remained effective despite repeated As2 O3 exposures. Oral As2 O3 maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Arsenic Trioxide/administration & dosage , Leukemia, Promyelocytic, Acute/therapy , Neoplasm Recurrence, Local/therapy , Remission Induction/methods , Administration, Oral , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Arsenic Trioxide/adverse effects , Ascorbic Acid/administration & dosage , Ascorbic Acid/adverse effects , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/etiology , Combined Modality Therapy/methods , Disease-Free Survival , Female , Headache/chemically induced , Headache/diagnosis , Headache/epidemiology , Hematopoietic Stem Cell Transplantation , Hong Kong/epidemiology , Humans , Leukemia, Promyelocytic, Acute/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Prospective Studies , Risk Factors , Severity of Illness Index , Survival Analysis , Time Factors , Transplantation, Autologous , Tretinoin/administration & dosage , Tretinoin/adverse effects , Young AdultABSTRACT
OBJECTIVE: The thrombopoietin mimetic eltrombopag has been used in clinical trials for the frontline and salvage treatment of aplastic anaemia (AA). Eltrombopag was investigated in AA patients on a non-trial all-comer basis. METHODS: Consecutive newly diagnosed and relapsed/refractory AA patients were treated with eltrombopag. RESULTS: In a 4.5-year period, 20 consecutive AA patients (newly diagnosed, N = 10; relapsed/refractory, N = 10) at a median age of 47 (22-84) years were treated with eltrombopag. For newly diagnosed patients, the frontline use of eltrombopag (concomitant medications: anti-thymocyte globulin, ATG, and ciclosporin, N = 4; ciclosporin, N = 5; nil, N = 1) at a median maximum dose of 150 (50-300)â mg/day led to an overall response rate (ORR) of 90% (trilineage: 60%; neutrophil: 20%; platelet: 10%). After a median follow-up of 47 (14-179) weeks, responses were maintained in all cases. In relapsed/refractory patients, eltrombopag at a median maximum dose of 150 (50-300)â mg/day led to an ORR of 50% (trilineage: 40%; neutrophil: 10%), with responses maintained after a median follow-up of 115 (53-253) weeks. Adverse effects included reversible skin pigmentation (observed in all patients taking eltrombopag at ≥150â mg/day), dyspepsia, and liver function derangement. CONCLUSION: In a routine haematological practice, the use of eltrombopag in AA patients was feasible, safe, and associated with very favourable responses.
Subject(s)
Anemia, Aplastic/drug therapy , Benzoates/therapeutic use , Hydrazines/therapeutic use , Pyrazoles/therapeutic use , Adult , Anemia, Aplastic/diagnosis , Benzoates/administration & dosage , Benzoates/adverse effects , Biomarkers , Combined Modality Therapy , Disease Management , Drug Resistance , Female , Hematopoietic Stem Cell Transplantation , Humans , Hydrazines/administration & dosage , Hydrazines/adverse effects , Male , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Recurrence , Thrombopoietin/administration & dosage , Thrombopoietin/adverse effects , Thrombopoietin/therapeutic use , Transplantation, Homologous , Treatment Outcome , Young AdultSubject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Molecular Targeted Therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Adult , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Asparaginase/administration & dosage , Drug Evaluation , Drug Resistance, Neoplasm , Fatal Outcome , Female , Humans , Lymphoma, Extranodal NK-T-Cell/drug therapy , Male , Middle Aged , Nivolumab , Programmed Cell Death 1 Receptor/immunology , Recurrence , Salvage TherapySubject(s)
Antibodies, Bispecific/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Diagnosis, Differential , Trichosporonosis/diagnosis , Varicella Zoster Virus Infection/diagnosis , Adult , Antibodies, Bispecific/therapeutic use , Antifungal Agents/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antiviral Agents/therapeutic use , Chemotherapy-Induced Febrile Neutropenia/complications , Female , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Recurrence , Salvage Therapy , Trichosporonosis/drug therapy , Trichosporonosis/etiologyABSTRACT
OBJECTIVE: To define the positron emission tomography/computed tomography (PET/CT) features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), a rare malignancy in European and North American populations and the most common form of primary intestinal T-cell lymphoma in Asian populations. METHODS: 18F-fluorodeoxyglucose (FDG) PET/CT findings of a cohort of MEITL patients were retrospectively analyzed. RESULTS: Eight men and four women with MEITL investigated by PET/CT at diagnosis and relapse were retrospectively analyzed. On presentation, the primary involved sites were the small bowel (N = 8), large bowel (N = 2), stomach (N = 1) and small and large bowels (N = 1). The uninvolved small bowel did not show increased FDG-avidity to suggest enteropathy. On presentation, lymph nodes and other organs were involved in seven cases (58%). The primary lesions were hypermetabolic except in one case, where the colonic lesion was eumetabolic. At relapse, the stomach and large bowel might be involved even if the primary tumours arose from the small bowel, and multiple extra-intestinal metastases occurred. Interestingly, thoracic structures and the brain were frequently involved (50% and 25% respectively). CONCLUSION: These findings showed that in contrast to classical enteropathy-associated T-cell lymphoma, where the small bowel is the exclusive primary site (owing to its origin from coeliac disease) and distant metastases even during relapse are exceptional, MEITL might on presentation and during relapse involve any part of the gut, and metastasize to multiple extra-intestinal sites.
Subject(s)
Lymphoma, T-Cell/diagnostic imaging , Positron Emission Tomography Computed Tomography/methods , Adult , Aged , Cohort Studies , Female , Humans , Lymphoma, T-Cell/pathology , Male , Middle Aged , Retrospective StudiesSubject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Hematopoietic Stem Cell Transplantation , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Salvage Therapy , Adult , Allografts , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Female , Humans , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/immunology , Nivolumab , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Proof of Concept Study , RecurrenceSubject(s)
Immunologic Factors/therapeutic use , Lenalidomide/therapeutic use , Lymphoma, Primary Effusion/drug therapy , Neoplasms, Second Primary/drug therapy , Aged, 80 and over , DNA, Viral/blood , Drug Eruptions/etiology , Drug Eruptions/prevention & control , Drug Monitoring , Eosinophilia/chemically induced , Eosinophilia/prevention & control , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/drug therapy , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/immunology , Gastrointestinal Stromal Tumors/pathology , Herpesvirus 4, Human/drug effects , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/isolation & purification , Herpesvirus 4, Human/metabolism , Humans , Immunologic Factors/adverse effects , Lenalidomide/adverse effects , Lymphoma, Primary Effusion/diagnostic imaging , Lymphoma, Primary Effusion/immunology , Lymphoma, Primary Effusion/virology , Male , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/immunology , Neoplasm Recurrence, Local/pathology , Neoplasms, Second Primary/diagnostic imaging , Neoplasms, Second Primary/immunology , Neoplasms, Second Primary/virology , Radiography, Thoracic , Treatment Outcome , Tumor Burden/drug effectsABSTRACT
Five patients with refractory/relapsed classical Hodgkin lymphoma (cHL), four having failed multiple lines of chemotherapy and brentuximab vedotin, were treated with low-dose pembrolizumab (median dose 100 mg, range: 100-200 mg, every 3 weeks). Complete response (CR) was achieved in four patients (80%), after a median cumulative dose of merely 495 (300-800) milligrams. Three CR patients have continued to receive pembrolizumab for a median of 16 (14-25) cycles, remaining in CR for a median of 18 (9-18) months. One CR patient underwent autologous hematopoietic stem cell transplantation and has remained in CR for 9 months. Partial response (PR) was achieved in one patient (20%), after a cumulative dose of 400 mg. The overall response rate was therefore 100% (CR: 80%; PR: 20%). Toxicity was virtually absent, with only grade 1 diarrhea and eczema each observed in one patient. Low-dose pembrolizumab was highly efficacious, achieving responses with minimal toxicity and at much lower costs.
Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Agents/administration & dosage , Hodgkin Disease/diagnosis , Hodgkin Disease/drug therapy , Secondary Prevention/methods , Adult , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
Natural killer (NK)/T-cell lymphomas failing L-asparaginse regimens have no known salvage and are almost invariably fatal. Seven male patients with NK/T-cell lymphoma (median age, 49 years; range, 31-68 years) for whom a median of 2 (range, 1-5) regimens (including l-asparaginase regimens and allogeneic hematopoietic stem-cell transplantation [HSCT] in 2 cases) failed were treated with the anti-programmed death 1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic, and molecular (circulating Epstein-Barr virus [EBV] DNA) criteria. Two patients achieved complete response (CR) in all parameters. Three patients achieved clinical and radiologic CRs, with two having molecular remission (undetectable EBV DNA) but minimal EBV-encoded RNA-positive cells in lesions comprising predominantly CD3+CD4+ and CD3+CD8+ T cells (which ultimately disappeared, suggesting they represented pseudoprogression) and one having detectable EBV DNA despite morphologic CR. Two patients achieved partial response (PR). After a median of 7 (range, 2-13) cycles of pembrolizumab and a follow-up of a median of 6 (range, 2-10) months, all five CR patients were still in remission. The only adverse event was grade 2 skin graft-versus-host disease in one patient with previous allogeneic HSCT. Expression of the PD1 ligand was strong in 4 patients (3 achieving CR) and weak in 1 (achieving PR). PD1 blockade with pembrolizumab was a potent strategy for NK/T-cell lymphomas failing l-asparaginase regimens.