ABSTRACT
BACKGROUND/AIM: Hairy cell leukemia (HCL) is a well-known lymphoproliferative disease with very effective treatment approaches primarily relying on purine analogues. However, these treatments are associated with profound and prolonged immunosuppression. Merkel cell carcinoma (MCC) is a rare and extremely aggressive skin tumor with an increased incidence in immunocompromised patients. CASE REPORT: We report a case of a patient with HCL who was diagnosed with MCC, while in remission following retreatment with pentostatin, which induced a profound decrease in CD4 (+) T-cells. CONCLUSION: Our case provides further evidence supporting the hypothesis of a significant association between immunosuppression and MCC pathogenesis.
Subject(s)
Carcinoma, Merkel Cell , Leukemia, Hairy Cell , Humans , Leukemia, Hairy Cell/pathology , Leukemia, Hairy Cell/drug therapy , Leukemia, Hairy Cell/diagnosis , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/diagnosis , Male , Skin Neoplasms/pathology , Skin Neoplasms/diagnosis , Remission Induction , Aged , Pentostatin/therapeutic use , BiopsyABSTRACT
The significance of serum beta-2 microglobulin (sß2m) in Hodgkin lymphoma (HL) is controversial. We analyzed 915 patients with HL, who were treated with ABVD or equivalent regimens with or without radiotherapy. Sß2m levels were measured by a radioimmunoassay (upper normal limit 2.4 mg/L). Sequential cutoffs (1.8-3.0 by 0.1 mg/L increments, 3.5 and 4.0 mg/L) were tested along with ROC analysis. The median sß2m levels were 2.20 mg/L and were elevated (>2.4 mg/L) in 383/915 patients (41.9%). Higher sß2m was associated with inferior freedom from progression (FFP) at all tested cutoffs. The best cutoff was 2.0 mg/L (10-year FFP 83% vs. 70%, p = 0.001), which performed better than the 2.4 mg/L cutoff ("normal versus high"). In multivariate analysis, sß2m > 2.0 mg/L was an independent adverse prognostic factor in the whole patient population. In multivariate overall survival analysis, sß2m levels were predictive at 2.0 mg/L cutoff in the whole patient population and in advanced stages. Similarly, sß2m > 2.0 mg/L independently predicted inferior HL-specific survival in the whole patient population. Our data suggest that higher sß2m is an independent predictor of outcome in HL but the optimal cutoff lies within the normal limits (i.e., at 2.0 mg/L) in this predominantly young patient population, performing much better than a "normal versus high" cutoff set at 2.4 mg/L.
ABSTRACT
Central nervous system (CNS) involvement is rare in primary mediastinal large B-cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system - international prognostic index (CNS-IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55-month median follow-up only 8 patients experienced CNS relapse as first event, always isolated. The 2-year cumulative incidence of CNS relapse (CI-CNSR) was 1.47% and remained unchanged thereafter. The CI-CNSR was not affected by the chemotherapy regimen (R-CHOP or R-da-EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2-year CI-CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS-IPI was also predictive (2-year CI-CNSR in high-risk vs. intermediate/low-risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement.
Subject(s)
Central Nervous System Neoplasms , Lymphoma, B-Cell , Lymphoma, Large B-Cell, Diffuse , Humans , Rituximab/therapeutic use , Incidence , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/epidemiology , Central Nervous System Neoplasms/pathology , Neoplasm Recurrence, Local/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Risk Factors , Cyclophosphamide , Vincristine , Doxorubicin , Chronic Disease , Central Nervous System/pathology , Lymphoma, B-Cell/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathologyABSTRACT
Serum ferritin (SF) is frequently elevated in classical Hodgkin lymphoma (cHL). We report on its prognostic significance in an unselected series of 529 cHL patients treated with state-of-the-art therapy. Higher baseline levels correlated with markers of advanced/aggressive disease. SF levels were significantly higher in male and older patients, those with high body mass index and mixed cellularity histology. The strongest correlation was recorded between SF and complement reactive protein (CRP) levels. Gender-specific SF cutoffs which provided the best discrimination in terms of freedom from progression (FFP) were identified. In multivariate analysis elevated SF levels, advanced stage and high lactate dehydrogenase (LDH) were independent prognostic factors of inferior FFP. SF also appears to retain independent prognostic significance for progression-free survival (PFS) but not for overall survival (OS). In conclusion, SF levels in cHL reflect disease activity and are associated with adverse patient outcomes.
Subject(s)
Hodgkin Disease , Biomarkers , Ferritins , Hodgkin Disease/diagnosis , Hodgkin Disease/therapy , Humans , Male , Prognosis , Progression-Free Survival , Retrospective StudiesSubject(s)
Diaphragm/pathology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Mediastinal Neoplasms/diagnosis , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/therapy , Mediastinal Neoplasms/mortality , Mediastinal Neoplasms/therapy , Neoplasm Staging , Prognosis , Symptom AssessmentABSTRACT
The expression patterns and prognostic significance of sterile alpha motif and HD domain-containing protein 1 (SAMHD1) protein in the neoplastic Hodgkin and Reed Sternberg (HRS) cells of Hodgkin lymphoma (HL) were investigated in a cohort of 154 patients with HL treated with standard regimens. SAMHD1 expression was assessed by immunohistochemistry using diagnostic lymph node biopsies obtained prior to treatment. Using an arbitrary 20% cut-off, SAMHD1 was positive in HRS cells of 48/154 (31·2%) patients. SAMHD1 expression was not associated with clinicopathologic parameters, such as age, gender, stage or histologic subtype. In 125 patients with a median follow-up of 90 months (7-401 months), SAMHD1 expression in HRS cells significantly correlated with inferior freedom from progression (FFP) (P = 0·025), disease-specific survival (DSS) (P = 0·013) and overall survival (OS) (P = 0·01). Importantly, in multivariate models together with disease stage, histology subtype and type of treatment as covariates, SAMHD1 expression retained an independent significant association with unfavourable FFP (P = 0·005) as well as DSS (P = 0·022) and OS (P = 0·018). These findings uncover the significance of a novel, adverse prognostic factor in HL that may have therapeutic implications since SAMHD1 inhibitors are now available for clinical use.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Hodgkin Disease , Lymph Nodes/enzymology , SAM Domain and HD Domain-Containing Protein 1/biosynthesis , Adolescent , Adult , Aged , Aged, 80 and over , Bleomycin/administration & dosage , Cell Line, Tumor , Dacarbazine/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Hodgkin Disease/drug therapy , Hodgkin Disease/enzymology , Hodgkin Disease/mortality , Humans , Male , Middle Aged , Neoplasm Staging , Survival Rate , Vinblastine/administration & dosageABSTRACT
End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/radiotherapy , Mediastinal Neoplasms/drug therapy , Mediastinal Neoplasms/radiotherapy , Adolescent , Adult , Aged , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Female , Humans , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Male , Mediastinal Neoplasms/diagnostic imaging , Middle Aged , Positron Emission Tomography Computed Tomography , Prednisone/therapeutic use , Retrospective Studies , Rituximab/therapeutic use , Treatment Outcome , Vincristine/therapeutic use , Young AdultSubject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Hodgkin Disease/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Mediastinal Neoplasms/drug therapy , Adult , Databases, Factual , Female , Follow-Up Studies , Hodgkin Disease/chemically induced , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Mediastinal Neoplasms/pathology , Prognosis , Survival RateSubject(s)
Hodgkin Disease , Cohort Studies , Disease-Free Survival , Hodgkin Disease/diagnosis , Humans , Prognosis , VinblastineABSTRACT
BACKGROUND: Only few studies have focused exclusively on patients with small lymphocytic lymphoma (SLL). PATIENTS AND METHODS: In the present report, 103 SLL patients were analyzed from both, clinical trials of the German Chronic Lymphocytic Leukemia Study Group and Greek centers, and emphasis was placed on the therapeutic strategy. The impact of lymph node characteristics, such as the presence of proliferation centers (PCs) on response and survival was also assessed. RESULTS: SLL patients included in clinical trials were treated mostly with fludarabine-based regimens while those in "real-life" were staged and treated mostly as patients with low-grade lymphomas. Our analysis showed a trend for better survival for patients with SLL without detectable PCs. CONCLUSION: Patients with SLL outside of clinical trials are usually treated as cases of lymphoma. In addition, this analysis supports published data regarding the adverse prognostic value of the presence of PCs in lymphoid nodes in SLL.
Subject(s)
Cell Proliferation/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Prognosis , Adult , Aged , Clinical Trials as Topic , Disease-Free Survival , Female , Germany , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymph Nodes/pathology , Male , Middle AgedSubject(s)
Bone Marrow Diseases/pathology , Immunotherapy/methods , Lymphoma, B-Cell, Marginal Zone/pathology , Meninges/pathology , Splenic Neoplasms/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Diagnostic Errors , Female , Humans , Injections, Spinal , Leukemia, Hairy Cell/diagnosis , Lymphoma, B-Cell, Marginal Zone/diagnosis , Lymphoma, B-Cell, Marginal Zone/drug therapy , Male , Methotrexate/administration & dosage , Remission Induction , Rituximab/administration & dosageABSTRACT
Cellular senescence is a stress response mechanism ensuring homeostasis. Its temporal activation during embryonic development or normal adult life is linked with beneficial properties. In contrast, persistent (chronic) senescence seems to exert detrimental effects fostering aging and age-related disorders, such as cancer. Due to the lack of a reliable marker able to detect senescence in vivo, its precise impact in age-related diseases is to a large extent still undetermined. A novel reagent termed GL13 (SenTraGorTM) that we developed, allowing senescence recognition in any type of biological material, emerges as a powerful tool to study the phenomenon of senescence in vivo. Exploiting the advantages of this novel methodological approach, scientists will be able to detect and connect senescence with aggressive behavior in human malignancies, such as tolerance to chemotherapy in classical Hodgkin Lymphoma and Langerhans Cell Histiocytosis. The latter depicts the importance of developing the new and rapidly expanding field of senotherapeutic agents targeting and driving to cell death senescent cells. We discuss in detail the current progress of this exciting area of senotherapeutics and suggest its future perspectives and applications.
Subject(s)
Antineoplastic Agents/therapeutic use , Cellular Senescence , Neoplasms/drug therapy , Animals , HumansSubject(s)
Antineoplastic Agents, Immunological/therapeutic use , Lymphoma, B-Cell, Marginal Zone/drug therapy , Rituximab/therapeutic use , Splenic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Drug Administration Schedule , Drug Evaluation , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Maintenance Chemotherapy , Male , Middle Aged , Progression-Free Survival , Remission Induction , Retrospective Studies , Treatment OutcomeABSTRACT
The outcome of patients with relapsed/refractory classical Hodgkin lymphoma (R/R cHL) after autologous stem cell transplantation (auto-SCT) is poor. Recently, the anti-CD30 monoclonal antibody-drug conjugate, brentuximab vedotin (BV), has shown remarkable activity in the setting of R/R cHL. In the pivotal phase II study, BV produced an overall response rate of 75% and a median progression-free survival of 6.7 months. Although these results have been reproduced by large registry studies, the impact of BV on the overall survival (OS) of patients with R/R cHL has not been addressed so far. The aim of this study was to examine the impact of BV on OS in the setting of post auto-SCT R/R cHL. Analysis was performed in a group of patients with R/R cHL after a previous auto-SCT reported in the Greek registry during the last 2 decades. By using a multivariate model and censoring patients at the time of subsequent allo-SCT or treatment with immune checkpoint inhibitors, we showed that treatment with BV in the posttransplant relapse setting has a positive impact on the outcome and results in significant improvement of OS. To our knowledge, this the first published study, addressing the impact of BV on the OS in the setting of posttransplant relapse.
Subject(s)
Hodgkin Disease/drug therapy , Immunoconjugates/therapeutic use , Adolescent , Adult , Aged , Brentuximab Vedotin , Cohort Studies , Female , Hodgkin Disease/therapy , Humans , Male , Middle Aged , Salvage Therapy , Stem Cell Transplantation , Survival Rate , Young AdultABSTRACT
BACKGROUND: SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenectomy represented the standard treatment modality until early 2000s. More than 90% of the patients present quick amelioration of splenomegaly related symptoms along with improvement of cytopenias related to hypersplenism. The median progression free survival was 8.25 years in the largest series of patients published so far, while the median 5- and 10- year OS were 84% and 67%, respectively. Responses to splenectomy are not complete since extrasplenic disease persists. Patients with heavy bone marrow infiltration, lymphadenopathy or other disease localization besides the spleen are not good candidates for splenectomy. Furthermore splenectomy is a major surgical procedure accompanied by acute perioperative complications as well as late toxicities mainly due to infections. For that reasons splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk. On the other hand rituximab monotherapy displays high efficacy with minimal toxicity. Several published series have shown an ORR more than 90%, with high CR rates (â¼50%). The 10-year PFS and OS were 63% and 85%, respectively in a series of 104 SMZL patients. The role of rituximab maintenance has been investigated by only one group. Based on these data, maintenance with rituximab further improved the quality of responses by increasing significantly the CR rates (from 42% at the end of induction to 71% at the end of maintenance treatment), as well as the duration of responses: 7-year PFS was 75% for those patients who received maintenance vs 39% for those who did not (p < 0.0004). However no difference in OS has been noticed between the two groups, so far. Summarizing the above data, it is obvious that Rituximab monotherapy is associated with high response rates, long response duration and favorable safety profile, rendering it as the treatment of choice in SMZL.
Subject(s)
Lymphoma, B-Cell, Marginal Zone/therapy , Rituximab/therapeutic use , Splenectomy , Splenic Neoplasms/therapy , Humans , Lymphoma, B-Cell, Marginal Zone/metabolism , Lymphoma, B-Cell, Marginal Zone/mortality , Lymphoma, B-Cell, Marginal Zone/pathology , Splenic Neoplasms/metabolism , Splenic Neoplasms/mortality , Splenic Neoplasms/pathology , Splenomegaly/metabolism , Splenomegaly/mortality , Splenomegaly/pathology , Splenomegaly/therapyABSTRACT
This retrospective study aimed to describe the Hellenic experience on the use of brentuximab vedotin (BV) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) given within its indication. From June 2011 to April 2015, ninety-five patients with R/R HL, who received BV in 20 centers from Greece, were analyzed. Their median age was 33 years, and 62% were males. Sixty-seven patients received BV after autologous stem cell transplantation failure, whereas 28 patients were treated with BV without a prior autologous stem cell transplantation, due to advanced age/comorbidities or chemorefractory disease. The median number of prior treatments was 4 and 44% of the patients were refractory to their most recent therapy. The median number of BV cycles was 8 (range, 2-16), and the median time to best response was the fourth cycle. Fifty-seven patients achieved an objective response: twenty-two (23%), a complete response (CR), and 35 patients (37%), a partial, for an overall response rate of 60%. Twelve patients (13%) had stable disease, and the remaining twenty-six (27%) had progressive disease as their best response. At a median follow-up of 11.5 months, median progression-free survival and overall survival were 8 and 26.5 months, respectively. Multivariate analysis showed that chemosensitivity to treatment administered before BV was associated with a significantly increased probability of achieving response to BV (P = .005). Bulky disease (P = .01) and response to BV (P <.001) were significant for progression-free survival, while refractoriness to most recent treatment (P = .04), bulky disease (P = .005), and B-symptoms (P = .001) were unfavorable factors for overall survival. Among the 22 CRs, 5 remain in CR with no further treatment after BV at a median follow-up of 13 months. In conclusion, our data indicate that BV is an effective treatment for R/R HL patients even outside clinical trials. Whether BV can cure a fraction of patients remains to be seen.