Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Brentuximab vedotin for relapsed or refractory Hodgkin lymphoma: experience in Turkey.

Current treatment modalities can cure up to 70-80 % of patients with classical Hodgkin lymphoma. Approximately, 20-30 % of patients require further treatment options. Brentuximab vedotin has been approved for the treatment of relapsed and refractory Hodgkin lymphoma. In the present study, we report the experience with brentuximab vedotin as single agent in 58 patients with relapsed or refractory Hodgkin lymphoma. The objective response rate was 63.5 % with 13 complete responders (26.5 %) among 49 patients evaluated at the early phase of treatment (2-5 cycles). Upon treatment prolongation (≥6 cycles), 37 patients achieved a final objective response rate of 32.4 % with 21.6 % of complete and 10.8 % of partial response. Overall survival at 12 months was 70.6 %, and progression-free survival at 12 months was 32.8 %. Median overall survival could not be reached and median progression-free survival was 7 months. While the median duration of response was 9 months in the whole cohort, it was 11.5 months in the complete responders. Complete response rates in patients treated with >3 chemotherapy regimens before brentuximab vedotin were significantly lower (p = 0.016). Fourteen patients were subsequently transplanted. In conclusion, brentuximab vedotin provided a bridge to transplantation in approximately one quarter of the patients. The declining response rates during the course of treatment suggest that transplantation should be implemented early during brentuximab vedotin treatment.

The relationship between ovarian volume and serum CA-125 levels.

PURPOSE: The aim of this study was to investigate the relationship between ovarian volume and serum CA-125 levels. MATERIALS AND METHODS: Serum CA-125 levels and ovarian volume were compared among the cases with benign ovarian neoplasms, primary epithelial ovarian cancer (EOC), controlled ovarian hyperstimulation, and ovarian hyperstimulation syndrome (OHSS). Also, the correlation between CA-125 levels and ovarian volume were evaluated in the presence of peritoneal fluid and/or peritoneal carcinomatosis. RESULTS: Although ovarian volume was not different among the groups, CA-125 levels were higher in the cases with EOC than with benign ovarian tumors (p = 0.001). Baseline CA-125 levels were not found to have increased while ovarian volume went up with controlled hyperstimulation in the infertile group (p = 0.555). However, uncontrolled hyperstimulation of the ovaries and the presence of peritoneal fluid caused an increase in the levels of CA-125 (p = 0.001). There was no correlation between ovarian volume and CA-125 levels in the cases with malignant ovarian tumors (r = 0.083). CONCLUSIONS: The results of this study have confirmed that CA-125 is a peritoneal marker and increased ovarian volume with benign ovarian neoplasms or controlled hyperstimulation does not increase CA-125 levels in the same way. The presence of peritoneal carcinomatosis and/or peritoneal fluid seems to be an important factor for high CA-125 levels in patients with epithelial ovarian cancer (EOC).

Comparison of different cyclin-dependent kinase inhibitors and KI-67 levels on survival and toxicity in breast cancer treatment.

OBJECTIVE: As cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors, which play a crucial role in the cell cycle, palbociclib and ribociclib are two novel drugs that are recently being used in the treatment of breast cancer. Despite targeting the same pathway, these agents have different molecular activities and processes. KI-67 is known to play a significant role in cell proliferation that has been related to prognosis. This study investigated the impact of palbociclib, ribociclib, and KI-67 on toxicity and survival in breast cancer treatment. PATIENTS AND METHODS: The study included 140 breast cancer patients in total. Patients were divided into groups based on the use of different CDK inhibitors and KI-67 values. Mortality, progression, treatment response rates, frequency, and severity of adverse events were assessed retrospectively. RESULTS: The patients in our study had an average age of 53.62±12.71 years, and 62.9% of them were diagnosed at an early stage. 34.3% (n=48) of the patients progressed after receiving treatment, while 19.3% (n=27) of the patients died. The median follow-up time was 576 days, the maximum follow-up time was 1,471 days, and the median time to progression was 301 days (min=28-max=713). Mortality, progression, and treatment response rate between two different CDK inhibitors or KI-67 groups revealed no statistically significant differences. CONCLUSIONS: Our data show a comparison between the effectiveness of palbociclib and ribociclib, and no noticeable difference is found in breast cancer patients' survival, progression, or severity of adverse effects. Likewise, there is no meaningful difference in KI-67 expression subgroups between progression and survival following treatment.

Comparison of the effectiveness of liposomal doxorubicin and gemcitabine in patients with platinum-sensitive recurrent ovarian cancer receiving third-line chemotherapy.

OBJECTIVE: In this retrospective study, we compared the effectiveness and reliability of the third-line chemotherapies gemcitabine and liposomal doxorubicin, in patients with platinum-sensitive ovarian cancer (OC). PATIENTS AND METHODS: The retrospective study included platinum-sensitive epithelial ovarian cancer patients who had previously received paclitaxel and carboplatin therapy. Between 2013-2021, cross-matched 45 patients who received gemcitabine and 48 who received liposomal doxorubicin as third-line therapy were compared based on clinicopathological characteristics, biomarkers, and blood cancer antigen (CA) 125 levels. Time to treatment failure, survival, and quality of life were additional objectives. RESULTS: The study included a total of 93 patients. The reported mean survival durations for treatments, 19.45 months for gemcitabine and 17 months for liposomal doxorubicin, did not statistically significantly differ (p=0.398). The mean CA 125 levels for the liposomal doxorubicin and gemcitabine groups after treatment were 54.4±11.4 U/ml and 54.7±11.1 U/ml, respectively. There was no noticeable difference between the treatments when comparing the postop CA 125 value (p=0.37). CONCLUSIONS: For both pegylated liposomal doxorubicin (PLD) and gemcitabine as single agents in the third line, our data revealed comparable effectiveness results, and there was no substantial difference in progression-free survival (PFS) for recurrent ovarian cancer. These therapies were tolerated with an expected incidence of hematological toxicities.

Preoperative evaluation, clinical characteristics, and prognostic factors of nongenital metastatic ovarian tumors: review of 48 patients.

OBJECTIVE: To evaluate the clinicopathologic characteristics, methods for preoperative evaluation, prognostic factors, and overall survival of nongenital ovarian metastases (NGOM). MATERIAL AND METHODS: Forty-eight patients with NGOM followed between January 2001 and January 2009 in Cukurova University Department of Gynecologic Oncology were included in the study. Clinical characteristics including demographics, preoperative imaging methods, endoscopic evaluations, tumor markers, histopathologic findings, prognostic factors, types of surgery, modalities for adjuvant therapy and survival were analyzed. RESULTS: The gastrointestinal tract is the most common location of the primary tumor; colonic origin was found in 41% of the patients (n = 20). All metastatic lesions were adenocarcinoma with 23% of these classified as Krukenberg and 29% as mucinous type adenocarcinoma. When the whole group was evaluated, median survival time was 15.7 months in patients and there were significant differences between the groups according to primary site. Histopathological subtypes and presence of peritoneal carcinomatosis affected the median survival. The significant prognostic factors were primary site and histopathologic subtypes of the NGOM. CONCLUSIONS: NGOM should be kept in mind to avoid inappropriate management and therapy in patients with surgically managed ovarian tumor, especially young patients with gastrointestinal complaints.

Severe pulmonary toxicity associated with fludarabine and possible contribution of rituximab.

Fludarabine is a nucleoside analogue used in the treatment of low-grade lymphoproliferative disorders and in conditioning regimens of non-myeloablative allogeneic stem cell transplantation. This is a relatively safe drug for clinical use but may cause side effects, some of which may be life-threatening. Here a case of severe pulmonary toxicity associated with fludarabine and a possible contribution of rituximab is presented and the literature reviewed.

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

Effects of pentoxifylline on the cytokines that may play a role in rejection and resistive index in renal transplant recipients.

Pentoxifylline (PTX) is a nonselective phosphodiesterase inhibitor that inhibits the production of TNFalpha and IL6 and IL-10 cytokines. In renal rejection TNFalpha, IL-6, and IL-10 may have important roles. In this study, 22 renal transplant recipients treated with tacrolimus, prednisolone, and mycophenolate mofetil were prescribed PTX (2 x 600 mg/d) for 3 months (GI), and 20 similar patients not receiving PTX were used as controls (GII). Stable subjects whose serum creatinine was lower than 1.8 mg/dL and were more than 6 months posttransplant, were enrolled into this study if the blood pressure was well controlled and there was no diabetes mellitus, infection, or inflammation. At the end of 3 months TNF-alpha decreased from 4.2 +/- 2.1 to 2.4 +/- 0.7 (P = .001) and 4.0 +/- 2.2 to 3.9 +/- 1.7 (P = .718), IL-10 also decreased from 3.90 +/- 1.9 to 2.38 +/- 0.6 (P = .001) and 4.02 +/- 1.6 to 3.82 +/- 1.5 (P = .225) in GI and GII, respectively. For IL-10 and TNF-alpha the alterations between baseline and the last visit of GI and GII were significant (P < .002 for all). Resistive index (RI) decreased in GI but the difference in alterations between baseline and the last visit of GI and GII was marginal. In summary IL-10 and TNF-alpha levels decreased in stable recipients treated with PTx. RI also decreased marginally secondary to PTx treatment. PTx was well tolerated and free side effects. PTx did not affect tacrolimus levels or other biochemical and hematological parameters.

Efficacy and safety of vardenafil in renal transplant recipients with erectile dysfunction.

Erectile dysfunction (ED) profoundly affects the quality of life. The prevalence of ED in renal transplant recipients is reported by high as 50% to 60%. We evaluated the efficacy and safety of vardenafil in these patients with ED as well as its effects on graft function and on cylosporine or tacrolimus concentrations. Thirty-nine recipients with ED and serum creatinine values<2 mg/dL were treated with vardenafil. ED was assessed using the self-administered International Index of Erectile Function (IIEF). ED was diagnosed by using penile color-Doppler ultrasonography and intracavernosal injection. Vardenafil efficacy was assessed by readministering the IIEF questionnaire after 4 weeks of therapy. Serum creatinine levels, creatinine clearances, and cyclosporine/tacrolimus concentrations were measured before and after vardenafil therapy. Twenty-one recipients with ED served as placebo controls and 15 without ED as another control group. The IIEF scores improved from 12.80+/-3.5 to 26.46+/-2.4 in vardenafil-treated patients with ED (P<.001). Renal function and cyclosporine/tacrolimus concentrations did not change with vardenafil therapy. Side effects were observed in 7 (18%) patients: headache in three, palpitations in one, flushing in two, and dyspepsia in one. This study demonstrated that ED improved with vardenafil in renal transplant recipients with ED. For 4 weeks vardenafil therapy was free of side effects. Renal function tests did not change. Also, no dose change in immunosuppressive drugs was required during 4 weeks of verdanafil therapy.

Bone Disease and Serum Fibroblast Growth Factor-23 Levels in Renal Transplant Recipients.

BACKGROUND: Posttransplantation bone disease develops commonly and results in important complications. In this study, we aimed to investigate the relationship between bone diseases and serum fibroblast growth factor-23 (FGF-23) in renal transplant recipients. METHODS: This study was conducted in 106 kidney transplant recipients (KTrs; group G1) and 30 patients with chronic kidney disease (group G2). Patients with fever, heart failure, angina pectoris, acute renal failure, malignant disease, or any gastrointestinal disease were excluded. KTrs were treated with triple immunosuppressive drugs including glucocorticoids. Complete blood count (CBC), blood urea nitrogen (BUN), creatinine, glomerular filtration rate (GFR, Modification of Diet in Renal Disease [MDRD] formula), lipid profile, calcium (Ca), phosphorous (P), parathormone (PTH), 25OHD3, serum levels of tacrolimus/cyclosporine, and intact FGF-23 were measured. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. RESULTS: The mean patient age was 40.1 ± 11.1 years and 39.2 ± 11.3 years in G1 and G2, respectively (P > .05). In G1 and G2, 76 and 15 patients were male, respectively. Compared with the G2 patients, G1 patients had lower body mass index (BMI), serum glucose levels, P, Mg, and Ca·P (P < .05 for all). T scores of the lumbar vertebrae/femur were -1.82 ± 0.99/-1.34 ± 0.89 and -1.13 ± 1.34/-0.51 ± 1.18 in G1 and G2 patients, respectively (P < .05 for all). The incidences of osteopenia/osteoporosis in the lumbar spine and femur were 50.9%/27.4% and 57.5%/10.4% in G1 and 16.6%/23.3%, and 40%/3.3% in G2. There were positive correlations between BMD and BMI, the time elapsed after renal transplantation, and GFR. In our study, a statistically significant relationship was found between lipid parameters and BMD, PTH, and 250HD3 levels, as well as use of corticosteroid and calcineurin inhibitors (P < .05 for all). In G1 and G2, BMD of the lumbar spine in patients with serum creatinine >1.5 mg/dL was lower than that in patients with serum creatinine <1.5 mg/dL. CONCLUSION: The association between age and BMD was found only in the femur of KTrs. No relationship was observed between serum FGF-23 levels and BMD values. In both groups, the BMD T score of the lumbar spine was lower compared to the BMD T score of the femur and in patients with serum creatinine >1.5 mg/dL. In long-term follow-up of renal transplantation by as much as 58 months, the incidence of bone disease such as osteoporosis/osteopenia was as high as 67% and was also higher than that of nontransplant patients with similar GFR. In addition to decreased renal function, dyslipidemia, inflammation, and continuing hypophosphatemia were also accompanied by decreased BMD as in cardiovascular disease in KTrs.

Dipyridamole for renal phosphate leak in successfully renal transplanted hypophosphatemic patients.

AIM AND BACKGROUND: Hyphosphatemia can be seen in renal transplant recipients. Hyperparathyroidism, glucocorticoid treatment, renal denervation and impairment of renal tubular phosphate reabsorption are the most common causes of hyphosphatemia in these patients. It is well-known that dipyridamole enhances renal tubular phosphate reabsorption in some clinical conditions. We did not find any information about the effect of dipyridamole in renal transplant recipients (RTRs) with hypophosphatemia. For this reason, we decided to give dipyridamole 11 RTRs with hypophosphatemia. PATIENTS AND METHODS: Eleven RTRs whose serum phosphate and creatinine levels were below 2.5 mg/dl and 2 mg/dl, respectively, were included in this study. None of the patients received drugs altering phosphate metabolism and they did not change their routine diets. Urinary phosphate excretion and tubular phosphate reabsorption (TPR) were calculated before and 3 weeks after dipyridamole treatment. RESULTS: The mean levels of serum-urine (daily) phosphate and TPR before dipyridamole treatment were 1.94 +/- 0.46 mg/dl, 7,187.5 +/- 1,833.49 mg/day and -2.78 +/- 0.62, respectively. After treatment, the mean levels of serum-urine phosphate and TPR were 2.73 +/- 0.46 mg/dl, 4,845.27 +/- 1,138.99 mg/day and -1.48 +/- 0.80, respectively. Serum and urine phosphate levels and TPR were found to be significantly different before and after dipyridamole therapy (p < 0.05). CONCLUSION: Short-term dipyridamole therapy increased TPR and serum phosphate levels and decreased urinary phosphate excretion. We did not observe negative effect on renal functions in these cases. Although the number of the cases included in this study is small, dipyridamole is an effective choice in management of hypophosphatemic RTRs.

Dyslipidemia and weight gain secondary to lifestyle changes in living renal transplant donors.

We evaluated renal function, lipid profile, body weight, and physical activity of living donors in long-term follow-up after nephrectomy. A total of 121 living donors were compared with 81 healthy subjects with normal renal function and no history of any surgery or disease. Before and after donor nephrectomies, we recorded age, body weight, systolic and diastolic blood pressures, serum creatinine, creatinine clearance, lipids, and serum glucose levels of the donors. Preoperative (baseline) and postoperative (last visit) physical activities of donors and controls were evaluated through the Modified Baecke Questionnaire (occupational activities, sports activities, leisure-time activities). There were no differences between donors and controls for age (P = .772), gender (P = .927), and follow-up period (P = .564). According to baseline levels, blood pressure and serum creatinine were increased and creatinine clearance was decreased (P < .001 for all). The mean increases in body weight (P = .012), LDL (P = .004), and triglyceride (P < .001) were higher in donors than in controls. But the mean decrease in HDL was not different between controls and donors (P = .057). Indices of sports and total activities were lower in donors than in controls on the last visit (P < .001). Indices of occupational and leisure-time activities were similar on the last visit in donors and in controls (P = .126, P = .083). The alterations in total cholesterol and total activity showed significant negative correlations in donors (r = -.581, P < .001). Also, the alterations in total cholesterol and body weight showed a significant correlation (r = .25, P = .02). We followed donors together with serum lipid levels, body weight, and total physical activities as well as blood pressure and renal function tests.

Sweet's syndrome accompanying leukaemia: seven cases and review of the literature.

Seven patients with Sweet's Syndrome (SS) accompanying leukaemia are presented. Six had acute myeloid leukaemia and one chronic myeloid leukaemia. SS developed during G-CSF therapy in two patients and following long periods of chemotherapy-associated neutropenia in two. This finding may suggest a possible role of G-CSF in the pathogenesis of SS. SS was diagnosed during the first presentation of three patients with leukaemia. Skin lesions on the lower extremities in two patients, widespread distribution in one, a local infiltration at the inguinal region and pleural effusion in one were interesting findings in our patients which are not usual for classical SS.

Granulocytic sarcoma as the cause of giant abdominal mass: diagnosis by fine needle aspiration and review of the literature.

Granulocytic sarcoma (GS) or chloroma is a neoplasia consisting of myeloid precursors in an extramedullary site. It is generally associated with myeloproliferative disorders especially with myeloid neoplasias. A young woman with huge abdominal mass due to GS associated with chronic myelocytic leukemia (CML) has been reported and literature is reviewed.

All trans retinoic acid as the possible cause of necrotizing vasculitis.

All trans retinoic acid (ATRA) is the drug of choice in the treatment of acute promyelocytic leukemia (APL). Generally, it is well tolerated but it has some side-effects, some of which may be fatal. The most severe side-effect of ATRA is ATRA syndrome; the other side-effects are rather dermatologic. Among these vasculitis has not been reported so far. We detected fever and skin lesions in two patients treated with ATRA where histopathologic examination revealed necrotizing vasculitis. With cessation of ATRA and corticosteroid administration, the lesions healed and fever quickly disappeared.

MUC1 expression in plasmacytoma.

Plasmacytoma (Pm) is a plasma cell (PC) neoplasia consisting of PCs and some of them show progression to multiple myeloma. But there is no clear indicators predicting this progression. In this study, MUC1 expression was evaluated in Pm cases to determine the predictive value and was compared with histopathologic grade which is known to be a prognostic indicator in Pm. Nine of 31 cases with Pm showed MUC1 expression. Only two of the 18 cases with mature morphology showed MUC1 expression while seven of 13 cases with immature morphology showed MUC1 expression and this was statistically significant (P<0.006). Additionally, four of 11 cases with BM involvement showed MUC1 expression while five of 20 cases without BM involvement showed MUC1 expression. There was a trend MUC1 expression with BM involvement but there was not statistically significant association between MUC1 expression and BM involvement. We found that MUC1 expression is associated with immature morphology which is an important prognostic indicator in Pm and by analogy MUC1 expression may be an additional prognostic indicator in patients with Pm.