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1.
Leuk Lymphoma ; : 1-9, 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39269267

ABSTRACT

Predictive prognostic scoring (PS) systems are not primarily applicable to elderly patients with classical Hodgkin lymphoma (cHL). The objective of this study was to develop a PS system for these patients. The derivation cohort (DC) was utilized for model development, consisting of 97 variables. The resulting algorithm was named as Hodgkin's Lymphoma Early Death in the Elderly within 12 months (HEDEL12). Internal and external validation cohorts (IVC and EVC) were employed for validation. A total of 286 patients were evaluated retrospectively. In DC 38 of 178 patients died within the first 12 months and overall survival (OS) at 12-month was 78.6%. Independent predictors of HEDEL12 were female sex, low albumin levels (<3.5 g/dL), and ECOG scores 2-4. According to HEDEL12 scores 0-1, OS at 12- months were 89.8% and 91.0% for IVC and EVC, respectively. The HEDEL12 scoring is useful in predicting the survival of advanced-stage cHL patients.


Predictive prognostic scoring (PS) systems are not applicable to elderly patients with classical Hodgkin lymphomaFemale sex, low albumin levels (<3.5 g/dL), and ECOG scores 2-4 are independent predictors of survival in older advanced stage cHL patients.

2.
Article in English | MEDLINE | ID: mdl-39264372

ABSTRACT

PURPOSE: To describe the long-term effects of an ASP among febrile neutropenia (FN) patients. METHODS: A quasi-experimental study was conducted between 2015 and 2023 at a tertiary care hospital in Istanbul, Türkiye. The ASP was implemented for FN patients, and the effects were assessed before and after the ASP interventions, which included FN clinical pathways and regular multi-disciplinary meetings with relevant healthcare workers. RESULTS: A total of 489 FN episodes of 290 patients were included, 42% were female, and the mean age was 56 years (SD: 15, range: 18-89 years). After the intervention, the rate of appropriate antimicrobial therapy at the levels of starting (p = 0.005), switching (p < 0.001), and de-escalation/discontinuation, (p < 0.001) significantly increased. Another positive impact of the ASP was a significant reduction in candidemia (from 4.88 to 0.74, p = 0.004), as well as a significant reduction in the 90-day mortality rate (from 19 to 5%, p < 0.001). In multivariate analysis, having a gram-negative bloodstream infection, prolonged days with fever, and a high risk for neutropenia were found to be significant predictors of 90-day mortality, while follow-up with ASP significantly reduced mortality. CONCLUSION: Implementation of ASP led to reduced candidemia and LOS without increasing mortality, even in a country with a high rate of antimicrobial resistance. Implementation of sustainable ASP for FN patients is critical in combating antimicrobial resistance.

3.
Lancet Oncol ; 25(4): 463-473, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38467131

ABSTRACT

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.


Subject(s)
Antineoplastic Agents , Leukemia, Lymphocytic, Chronic, B-Cell , Adult , Humans , Male , Female , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Antineoplastic Agents/adverse effects , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Sulfonamides/adverse effects , Pathologic Complete Response , Antineoplastic Combined Chemotherapy Protocols/adverse effects
4.
Expert Rev Hematol ; 16(12): 991-1015, 2023.
Article in English | MEDLINE | ID: mdl-37897182

ABSTRACT

INTRODUCTION: Classical Hodgkin lymphoma (cHL) is a curable disease, with durable remission achieved in about 80% of patients following first-line treatment. Three new drugs were introduced to the daily use in cHL: brentuximab vedotin (BV), nivolumab, and pembrolizumab. All three drugs were initially approved for the treatment of relapsed/refractory cHL (RRHL) and with their promising outcomes, they are now incorporated in different stages of the treatment. AREAS COVERED: We performed a literature search using PubMed on all cHL studies investigating BV and CPIs within the past 10 years. We analyzed literature to presume the sequencing of these novel agents. EXPERT OPINION: Addition of BV or nivolumab to AVD backbone in the frontline setting showed promising activity in advanced stage cHL. BV and CPIs combined with chemotherapy in the second-line treatment of cHL are evaluated in phase 2 studies and comparable results are reported. The results of BrECADD, with good efficacy and toxicity profile, should be followed. Pembrolizumab was shown to be more effective in RRHL compared to BV in patients who have relapsed post-ASCT or ineligible for ASCT. BV is used in post-ASCT maintenance in high-risk cases, although its role will be questioned as it is increasingly used in the frontline treatment.


Subject(s)
Hodgkin Disease , Immunoconjugates , Humans , Hodgkin Disease/pathology , Nivolumab/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Brentuximab Vedotin/therapeutic use , Immunoconjugates/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects
5.
Hematol Oncol ; 41(4): 663-673, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37211991

ABSTRACT

Glofitamab is a CD3xCD20 bi-specific antibody with two fragments directed to the CD20 antigen and a single CD3-binding fragment. Encouraging response and survival rates were recently reported in a pivotal phase II expansion trial conducted in patients with relapsed/refractory (R/R) B-cell lymphoma. However, the real-world data of patients of all ages with no strict selection criteria are still lacking. Herein, this retrospective study aimed to evaluate the outcomes of diffuse large B-cell lymphoma (DLBCL) patients who received glofitamab via compassionate use in Turkey. Forty-three patients from 20 centers who received at least one dose of the treatment were included in this study. The median age was 54 years. The median number of previous therapies was 4, and 23 patients were refractory to first-line treatment. Twenty patients had previously undergone autologous stem cell transplantation. The median follow-up time was 5.7 months. In efficacy-evaluable patients, 21% and 16% of them achieved complete response and partial response, respectively. The median response duration was 6.3 months. The median progression-free survival (PFS) and overall survival (OS) was 3.3 and 8.8 months, respectively. None of the treatment-responsive patients progressed during the study period, and their estimated 1-year PFS and OS rate was 83%. The most frequently reported toxicity was hematological toxicity. Sixteen patients survived, while 27 died at the time of the analysis. The most common cause of death was disease progression. One patient died of cytokine release syndrome during the first cycle after receiving the first dose of glofitamab. Meanwhile, two patients died due to glofitamab-related febrile neutropenia. This is the largest real-world study on the effectiveness and toxicity of glofitamab treatment in R/R DLBCL patients. The median OS of 9 months seems promising in this heavily pretreated group. The toxicity related mortality rates were the primary concerns in this study.

6.
Ann Hematol ; 102(1): 133-140, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36401621

ABSTRACT

Polatuzumab vedotin (Pola) with bendamustine and rituximab (BR) is a promising option for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We analyzed the data of 71 R/R DLBCL patients who had been treated with Pola-BR in the named patient program from March 2018 to April 2021 from 32 centers in Turkey. All patients received up to six cycles of Pola 1.8 mg/kg, rituximab 375 mg/m2 on day 1, and bendamustine 90 mg/m2 on days 1-2 of each cycle. Median age at Pola-BR initiation was 55 (19-84). The overall response rate was 47.9%, including 32.4% CR rate when a median of 3 cycles was applied. With a median follow-up of 5 months, the median OS was 5 months. Grade 3-4 neutropenia and thrombocytopenia were the most common hematological toxicities. The real-world data from our cohort showed the Pola-BR is an effective option with a manageable toxicity profile.


Subject(s)
Immunoconjugates , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , Rituximab/adverse effects , Bendamustine Hydrochloride/adverse effects , Turkey/epidemiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma, Non-Hodgkin/drug therapy , Immunoconjugates/therapeutic use , Lymphoma, Large B-Cell, Diffuse/pathology
7.
Hematol Oncol ; 41(1): 97-107, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36314897

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/pathology
8.
Leuk Lymphoma ; 63(14): 3317-3330, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36200380

ABSTRACT

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB-IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9-20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum.Clinical trial registration: NCT03327571.


Subject(s)
Hematopoietic Stem Cell Transplantation , Hodgkin Disease , Adult , Humans , Hodgkin Disease/pathology , Retrospective Studies , Neoplasm Recurrence, Local/pathology , Cisplatin , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Cytarabine , Stem Cell Transplantation , Salvage Therapy , Etoposide
10.
Turk J Haematol ; 39(3): 206-210, 2022 08 25.
Article in English | MEDLINE | ID: mdl-35848614

ABSTRACT

Objective: Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented. Materials and Methods: A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study. Results: Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up. Conclusion: Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial.


Subject(s)
Lymphoma, Non-Hodgkin , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Receptors, Chimeric Antigen , Antigens, CD19 , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/methods , Lymphoma, Non-Hodgkin/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/therapeutic use , Turkey/epidemiology
11.
Turk J Haematol ; 39(4): 254-261, 2022 12 01.
Article in English | MEDLINE | ID: mdl-35657203

ABSTRACT

Objective: Redditux® (RED), as a biosimilar rituximab, was approved in Turkey for all indications of the original Mabthera® (MAB) in March 2018. The aim of our study was to evaluate the efficacy and safety of RED in de novo diffuse large B-cell lymphoma. Materials and Methods: Fifty-one patients received RED combined with the CHOP regimen. The median follow-up was 31 months. The historical control group included 219 patients treated with the MAB-CHOP regimen and the median follow-up time was 38 months. We compared the response rates and survival outcomes of these RED-CHOP and MAB-CHOP cohorts. Results: In the RED cohort, the overall response rate (ORR) at the end of the treatment protocol was 86%, with 37 (72.5%) cases of complete response (CR) and 7 (13.5%) cases of partial response (PR). In the historical MAB cohort, the ORR was 84%, with CR and PR rates of 82% and 2%, respectively. The 24-month progression-free survival (PFS) rates were 73.76% (95% confidence interval [CI]: 0.59-0.84) and 85.2% (95% CI: 0.79-0.90) for the RED and MAB cohorts, respectively (p=0.0106). The 24-month overall survival rates were 78.4% (95% CI: 0.64-0.87) and 81.4% (95% CI: 0.75-0.86) for the RED and MAB cohorts, respectively (p=0.7461). For patients with high revised International Prognostic Index scores, 24-month PFS was 45.5% (95% CI: 0.17-0.71) and 63% (95% CI: 0.37-0.80) for the RED and MAB cohorts, respectively (p=0.0711). In the RED cohort, central nervous system (CNS) relapse was significantly increased compared to the MAB cohort (10% vs. 1.83%, p=0.004). Among the RED cohort, bone involvement at the time of diagnosis was a risk factor for CNS relapse (p=0.028). Thirteen patients died in follow-up. There were no serious adverse events causing the cessation of the drugs. Conclusion: RED has an ORR similar to that of MAB. However, PFS rates were worse in the RED cohort. Additionally, CNS relapse ratio was a major concern for our RED cohort. Large prospective controlled studies and real-life data with longer follow-up are needed to document the non-inferiority of RED compared to MAB.


Subject(s)
Biosimilar Pharmaceuticals , Lymphoma, Large B-Cell, Diffuse , Humans , Rituximab/therapeutic use , Biosimilar Pharmaceuticals/adverse effects , Prospective Studies , Antibodies, Monoclonal, Murine-Derived/adverse effects , Neoplasm Recurrence, Local/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Vincristine/adverse effects , Cyclophosphamide/therapeutic use , Prednisone/therapeutic use , Doxorubicin/adverse effects , Disease-Free Survival
12.
Neurohospitalist ; 12(2): 307-311, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35419156

ABSTRACT

Here we report a challenging case of a 52-year-old man presenting with subacute constipation, urinary retention, impotence, absent Achilles reflexes, and hypoesthesia in S2-S5 dermatomes. We review the clinical decision-making as the symptoms evolved and diagnostic testing changed over time. Once the diagnosis is settled, we discuss the sign and symptoms, additional diagnostic tools, treatment options and prognosis.

13.
J Chemother ; 34(3): 190-198, 2022 May.
Article in English | MEDLINE | ID: mdl-34514960

ABSTRACT

The prognosis is poor for relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL) patients. The brentuximab vedotin (Bv) and bendamustine (B) combination has been used as a preferable salvage regimen in R/R cHL patient trials. We retrospectively evaluated response rates, toxicities, and the survival in R/R cHL patients treated with the BvB combination. In a multi-centre real-life study, 61 R/R HL patients received intravenous doses of 1.8 mg/kg Bv on the first day plus 90 mg/m2 B on the first and second days of a 21-day cycle as a second-line or beyond-salvage regimen. Patients' median age at BvB initiation was 33 (range: 18-76 years). BvB was given as median third-line treatment for a median of four cycles (range: 2-11). The overall and complete response rates were 82% and 68.9%, respectively. After BvB initiation, the median follow-up was 14 months, and one- and two-year overall survival rates were 85% and 72%, respectively. Grade 3/4 toxicities included neutropenia (24.6%), lymphopenia (40%), thrombocytopenia (13%), anaemia (13%), infusion reactions (8.2%), neuropathy (6.5%), and others. The BvB combination could be given as salvage regimen aiming a bridge to autologous stem cell transplant (ASCT), in patients relapse after ASCT or to transplant-ineligible patients with manageable toxicity profiles.


Subject(s)
Hodgkin Disease , Immunoconjugates , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bendamustine Hydrochloride/adverse effects , Brentuximab Vedotin , Hodgkin Disease/drug therapy , Humans , Immunoconjugates/adverse effects , Neoplasm Recurrence, Local/drug therapy , Retrospective Studies , Salvage Therapy , Treatment Outcome
14.
Am J Blood Res ; 11(4): 427-437, 2021.
Article in English | MEDLINE | ID: mdl-34540352

ABSTRACT

Coronavirus disease 2019 (COVID-19) has led to a global pandemic that has also challenged the management of various other life-threatening conditions, such as malignant disorders. In this study, we present the clinical features and treatment outcomes of twenty-seven COVID-19 positive patients with leukemia across seven different centers in Istanbul. From March 1st to December 31st 2020, 116 patients were diagnosed with acute leukemia. Thirty-two cases with acute lymphocytic leukemia (ALL), 82 cases with acute myeloid leukemia (AML), and 2 cases with mixed phenotype acute leukemia (MPAL) were identified. Of the 27 patients with the COVID-19 infection, seven patients had ALL, 19 patients had AML and one patient had MPAL. The mortality rate was 37% among the patients with AML, whereas there were no deaths in the ALL group. The mortality rate of AML patients with the COVID-19 infection was higher compared to cases without the infection (P<0.05). We could not detect any significant difference in the ALL cohort. This study, which includes one of the largest acute leukemia series in literature proved that acute myeloid leukemia patients with the COVID-19 infection have worse outcomes than patients without the infection. The high mortality among patients with acute leukemias hospitalized with COVID-19 highlight the need for aggressive infection prevention, increased surveillance and protective isolation and even modification of the therapy, in case of minimal residual disease (MRD) negativity.

15.
Turk J Haematol ; 38(4): 273-285, 2021 12 07.
Article in English | MEDLINE | ID: mdl-34448556

ABSTRACT

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.


Subject(s)
Adenine/analogs & derivatives , Leukemia, Lymphocytic, Chronic, B-Cell , Piperidines , Adenine/adverse effects , Aged , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Middle Aged , Piperidines/adverse effects , Retrospective Studies , Treatment Outcome , Turkey
16.
Arch Med Sci ; 17(4): 920-927, 2021.
Article in English | MEDLINE | ID: mdl-34336021

ABSTRACT

INTRODUCTION: We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey. MATERIAL AND METHODS: In this retrospective study, we included relapsed/refractory Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients who underwent multiple lines of chemotherapy. The primary endpoint was to determine the objective response and toxicity. RESULTS: Ninety-nine patients with a median age of 59.8 years were included in the study. Eighty-one patients had NHL (follicular lymphoma: 10, diffuse large B-cell lymphoma: 27, mantle-cell lymphoma: 18, marginal zone lymphoma: 9, small lymphocytic lymphoma/chronic lymphocytic leukemia: 17) and 18 patients had HL. The patients had previously received a median of three lines of chemotherapy (range: 2-8) except autologous stem cell transplantation (ASCT); 19 patients (HL: 11, NHL: 8) had undergone ASCT. The objective response rate (ORR) was 74.3%, the complete response rate was 57% (= 53), and the partial response rate was 16.6% ( = 19). The overall survival (OS) rate at 1 year was 74.6%. The progression-free survival (PFS) rate at 1 year was 62.5%. The most common side effects were lymphopenia, anemia and neutropenia. Side effects which were observed as grade 3 and higher levels were lymphopenia (14.1%), neutropenia (10.1%) and fatigue (7.1%). CONCLUSIONS: Objective response rate of bendamustine was found to be 74.3% in relapsed/refractory HL and NHL patients. It appears to be an effective option as a salvage treatment for patients who have previously received multiple lines of therapy.

17.
Hematol Oncol ; 39(4): 498-505, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34171130

ABSTRACT

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease <12 months (n = 61), lack of complete response (CR) to the last salvage regimen (n = 51), and having had at least two salvage regimens (n = 29). At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in 6, and SD in 3 patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-year PFS and OS rates were 67.75% (95% confidence interval [CI]: 0.55-0.77) and 87.61% (95% CI: 0.76-0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV-naïve and BV-exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to adverse event in 12 patients. Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55-0.75) with an acceptable toxicity profile.


Subject(s)
Brentuximab Vedotin/therapeutic use , Hematopoietic Stem Cell Transplantation/methods , Hodgkin Disease/drug therapy , Transplantation Conditioning/methods , Adolescent , Adult , Aged , Brentuximab Vedotin/pharmacology , Humans , Middle Aged , Retrospective Studies , Young Adult
18.
Clin Nucl Med ; 46(8): 656-658, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34034308

ABSTRACT

ABSTRACT: We created our first national clinical protocol of 177Lu-CXCR4 therapy for patient who have failed to respond to current therapy options. We also calculated the kidney, liver, and tumor dosimetry. The kidney's mean absorbed dose was calculated to be 0.45 Gy/GBq, the calculated radiation absorbed dose of the liver was 0.63 Gy/GBq, and the radiation absorbed doses of the tumors vary between 9.2 and 82 Gy/GBq. 177Lu-CXCR4 therapy produced a promising clinical response in our patient in acceptable radiation dose limits as a treatment option in heavily pretreated patients with advanced multiple myeloma.


Subject(s)
Lutetium/therapeutic use , Multiple Myeloma/radiotherapy , Radioisotopes/therapeutic use , Receptors, CXCR4/metabolism , Female , Humans , Isotope Labeling , Male , Middle Aged , Radiometry , Recurrence
19.
Indian J Pathol Microbiol ; 64(1): 149-151, 2021.
Article in English | MEDLINE | ID: mdl-33433427

ABSTRACT

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia. The coexistence of CLL and papillary thyroid carcinoma (PTC) is extremely rare. PTC sometimes shows microscopic vascular invasion but rarely cause a tumor thrombus in the internal jugular vein (IJV). It is also rare to find both differentiated and poorly differentiated types of thyroid cancer in the same metastatic location. We report a case of 63-year-old Turkish man with history of CLL who had CLL/SLL involvement and PTC metastasis in the same lymph node. Additionally, there was macroscopic metastasis to the IJV with poorly differentiated areas in the removed tumor thrombus. Patient was treated with total thyroidectomy, left radical neck dissection, resection of the left IJV segment that contained the tumor thrombus and radioactive iodine (RAI) therapy. Furthermore, metastatic lesions were found in the brain, lung and bone. Radiotherapy and chemotherapy were performed. However, our patient died approximately 12 months after thyroidectomy. To our knowledge, our present report is the first description with its current features.


Subject(s)
Adenocarcinoma/diagnosis , Jugular Veins/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymph Nodes/pathology , Thyroid Cancer, Papillary/diagnosis , Thyroid Cancer, Papillary/secondary , Cell Differentiation , Humans , Iodine Radioisotopes/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local , Thyroid Cancer, Papillary/drug therapy , Thyroid Cancer, Papillary/surgery , Thyroidectomy
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