Prognostic and predictive value of tumoral DNA damage repair protein expression in patients with resected pancreatic cancer.

OBJECTIVE: DNA damage repair (DDR) gene mutations gained interest in the treatment of metastatic pancreatic cancer (PC) patients, but their relevance in adjuvant setting is not well characterized. We assessed the prognostic and predictive potential of tumoral expression of DDR proteins along with clinical and tumor characteristics in patients with resected PC. PATIENTS AND METHODS: Patients with PC who underwent pancreatic resection in our institution between 2005 and 2017 were retrospectively retrieved. Tumoral expression of a panel of DDR proteins including BRCA1, BRCA2, ATM, and p53 with immunohistochemistry was evaluated and association with patient and tumor features as well as prognosis was assessed. RESULTS: 130 patients were included in the study. The median age was 61 and 66% were males, 57% had lymph node involvement and 17% had a vascular invasion. 25 patients (19%) had thrombosis at the time of diagnosis. Median overall survival (OS) and disease-free survival (DFS) were 21.6 and 11.8 months, respectively. More advanced disease stage (HR: 3.67 95% CI 1.48-9.12, p = 0.005), presence of thrombosis (HR: 2.01 95% CI 1.04-3.89, p = 0.039), high BRCA1 expression (HR: 2.25, 95% CI 1.13-5.48, p = 0.023) and high post-operative CA 19-9 level (>100 IU/ml) (HR:2.61 95% CI 1.40-4.89, p = 0.003) were associated with shorter DFS. BRCA2, ATM, and p53 expression were not associated with DFS or OS. Adjuvant gemcitabine-cisplatin regimen was not associated with increased DFS or OS in the whole group, neither in low or high expressors of BRCA1, BRCA2, ATM or p53. CONCLUSION: Contrary to BRCA2, ATM, and P53, BRCA1 expression may be beneficial for prognosis in resected pancreatic cancer, while no predictive role was observed in terms of adjuvant platinum efficacy.

Sarcopenia and anthracycline cardiotoxicity in patients with cancer.

BACKGROUND: Several studies have suggested that sarcopenia is associated with an increased treatment toxicity in patients with cancer. The aim of this study is to evaluate the relationship between sarcopenia and anthracycline-related cardiotoxicity. METHODS: Patients who received anthracycline-based chemotherapy between 2014 and 2018 and had baseline abdominal CT and baseline and follow-up echocardiography after anthracycline treatment were included. European Society of Cardiology ejection fraction criteria and American Society of Echocardiography diastolic dysfunction criteria were used for definition of cardiotoxicity. Sarcopenia was defined on the basis of skeletal muscle index (SMI) and psoas muscle index (PMI) calculated on CT images at L3 and L4 vertebra levels. RESULTS: A total of 166 patients (75 men and 91 women) were included. Sarcopenia was determined in 33 patients (19.9%) according to L3-SMI, in 17 patients (10.2%) according to L4-SMI and in 45 patients (27.1%) according to PMI. 27 patients (16.3%) developed cardiotoxicity. PMI and L3-SMI were significantly associated with an increased risk of cardiotoxicity (L3-SMI: HR=3.27, 95% CI 1.32 to 8.11, p=0.01; PMI: HR=3.71, 95% CI 1.58 to 8.73, p=0.003). CONCLUSIONS: This is the first study demonstrating a significant association between CT-diagnosed sarcopenia and anthracycline-related cardiotoxicity. Routine CT scans performed for cancer staging may help clinicians identify high-risk patients in whom closer follow-up or cardioprotective measures should be considered.

Prognosis of Liposarcoma Patients in Modern ERA: Single-Center Experience.

Objective Liposarcomas are relatively rare tumors. Prognostic and predictive factors and treatment options are limited. We herein presented our 10-year experience with liposarcomas. Materials and Methods Adult patients with liposarcoma treated between 2005 and 2015 in our center were included. Demographic and clinicopathologic features of patients were retrieved from patient files. Statistical Analyses Outcomes in terms of disease-free survival (DFS) and overall survival (OS) were assessed along with potential prognostic factors using Kaplan-Meier analyses. Results A total of 88 patients were included. The median age was 52. Rates of well-differentiated (WDLS), dedifferentiated (DDLS), myxoid (MLS), and pleomorphic liposarcomas (PLS) were 42, 9.1, 37.5, and 4.5%, respectively. Only 10% of patients had high-grade tumors and 93% had localized disease. Ninety-six percent of patients ( n = 84) underwent surgery. Adjuvant chemotherapy was delivered to 16 patients. The most common regimen was ifosfamide-doxorubicin. Recurrences were observed in 30 patients, 21 had local, and 9 had distant metastasis. Five-year DFS of patients with the localized disease was 68%. All patients with PLS had relapses and those had the highest distant relapse rates among all subtypes. Multivariate analysis showed T stage and grade were associated with DFS. Five-year OS of the entire population was 68%. Five-year OS was 79, 76, 50, and 0% in WDLS, MLS, DDLS, and PLS, respectively ( p = 0.002). Conclusion Management of liposarcomas is still challenging. Surgery is the mainstay of treatment. Novel effective therapies are needed, particularly in advanced disease settings.

Efficacy analyses of axitinib and nivolumab in metastatic renal cell carcinoma after failure of targeted therapy: which is better?

PURPOSE: The objective of the present study was to compare the efficacy of axitinib and nivolumab in metastatic renal cell carcinoma (mRCC) previously treated with targeted therapy. METHODS: A total of 79 patients were enrolled (39 patients in axitinib group, 40 patients in nivolumab group). Survival outcomes of patients, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method and compared with the log-rank test. The associations between potential prognostic variables and OS were evaluated in univariate and multivariate Cox regression analyses. RESULTS: The median PFS and OS of all cohort were 8.1 and 36.6 months, respectively. Higher PFS and OS were evaluated in axitinib group than nivolumab group (PFS: 9.4 months vs 6.3 months, p=0.386; OS: 38.2 months vs 36.6 months, p=0.671, respectively). Patients treated with axitinib had numerically higher objective response rate (ORR) and disease control rate (DCR) than those treated with nivolumab (ORR: 43.6% vs 27.6%, p=0.157, DCR: 74.4% vs 62.5%, p=0.157, respectively). Multivariate analysis revealed that the independent predictors of OS were higher tumor grade (hazard ratio [HR]: 6.178, p=0.004), worse response to axitinib and nivolumab (HR:4.902, p=0.011), the presence of lung metastasis (HR:15.637, p=0.002) and the presence of liver metastasis (HR:12.010, p=0.001). CONCLUSION: Comparable survival outcomes were detected in the axitinib and nivolumab groups. However, head to head comparisons are needed to highlight the relative efficacy of these therapies in mRCC.

Evaluation of early unplanned readmissions and predisposing factors in an oncology clinic.

BACKGROUND: Unplanned readmission in the first 30 days after discharge is an important medical problem, although the data on cancer patients is limited. So we planned to evaluate the rates and causes of early readmissions and the predisposing factors. METHODS: Patients hospitalized in Hacettepe University Oncology services between August 2018 and July 2019 were included. The demographic features, tumor stages, regular drugs, last laboratory parameters before discharge, and readmissions in the first 30 days after discharge were recorded. The predisposing features were evaluated with univariate and multivariate analyses. RESULTS: A total of 562 hospitalizations were included. The mean age of the patients was 58.5 ± 14.5 years. Almost 2/3 of the hospitalizations were due to symptom palliation and infections. Eighty-three percent of the patients had advanced disease, and over 60% had an ECOG score of 2 and above. In the first 30 days after discharge, 127 patients were readmitted (22.6%). Advanced stage disease, presence of polypharmacy (5 or more regular drugs), hospitalization setting (emergency department (ED) vs. outpatient clinic), and hypoalbuminemia (< 3 gr/dL) were associated with a statistically significant increase in the risk of readmission. Among these factors, advanced-stage disease (HR: 2.847, 95% CI: 1.375-5.895), hospitalization from ED (HR: 1.832, 95% CI: 1.208-2.777), and polypharmacy (HR: 1.782, 95% CI: 1.173-2.706) remained significant in multivariate analyses. CONCLUSIONS: In this study, 22% of cancer patients had early readmissions. The readmission risk increased in patients with advanced disease, hospitalization from ED, and polypharmacy. The optimal post-discharge plan may reduce readmissions in all oncology patients, with priority for these patient groups.

COVID-19 pandemic: changes in cancer admissions.

BACKGROUND: COVID-19 pandemic could create a collateral damage to cancer care denoting disruptions in care due to a significant burden on healthcare and resource allocations. Herein, we evaluate the early changes in the inpatient and outpatient oncology clinics to take a snapshot of this collateral damage at Hacettepe University Cancer Institute. METHODS: Patients applying the outpatient clinic and outpatient palliative care (OPC) clinic for the first time and patients admitted to inpatient wards in the first 30 days after the first case of COVID-19 in Turkey were evaluated. These data were compared with data from the same time frame in the previous 3 years. RESULTS: The mean number of daily new patient applications to the outpatient clinic (9.87±3.87 vs 6.43±4.03, p<0.001) and OPC clinic (3.87±1.49 vs 1.13±1.46, p<0.001) was significantly reduced compared with the previous years. While the number of inpatient admissions was similar for a month frame, the median duration of hospitalisation was significantly reduced. The frequency of hospitalisations for chemotherapy was higher than in previous years (p<0.001). By comparison, the rate of hospitalisations for palliative care (p=0.028) or elective interventional procedures (p=0.001) was significantly reduced. CONCLUSION: In our experience, almost all domains of care were affected during the pandemic other than patients' systemic treatments. There were significant drops in the numbers of newly diagnosed patients, patients having interventional procedures and palliative care services, and these problems should be the focus points for the risk mitigation efforts for prevention of care disruptions.

Relationship of lymph node status with survival and recurrence among women with endometrial cancer.

OBJECTIVE: To explore the relationship of lymph node ratio (LNR) and other lymph node parameters with disease-free (DFS) and overall (OS) survival among women with endometrial cancer. METHODS: Retrospective analysis of data of women diagnosed with endometrial cancer at Hacettepe University Hospitals, Ankara, Turkey, between 2003 and 2013. Women who had their surgical procedure, pathology review, and follow-up at Hacettepe University Hospitals were included in the study. Receiver operator characteristic (ROC) curve analysis was used to determine the threshold LNR associated with survival. RESULTS: Overall, 376 women were included in the study. A higher number of excised metastatic lymph nodes was associated with decreased survival. ROC curve analysis determined a threshold LNR of 0.03. Women with LNR higher than 0.03 had decreased DFS (P<0.001) and OS (P<0.001) relative to those with LNR of 0.03 or lower. LNR of 0.1 was found to be a significant cutoff value for DFS (P=0.023) and OS (P=0.036) among women with at least one metastatic lymph node. CONCLUSION: LNR may be used as a prognostic tool in endometrial cancer. Future studies will help to define a precise threshold of LNR in order to implement this prognostic factor in daily practice.

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

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

Comparison of clinical and PET-derived prognostic factors in patients with non-Hodgkin lymphoma: a special emphasis on bone marrow involvement.

OBJECTIVE: In patients with non-Hodgkin lymphoma (NHL), we investigated F FDG PET/computed tomography (CT) parameters, clinical findings, laboratory parameters, and bone marrow involvement (BMI) status for predictive methods in progression-free survival (PFS) and overall survival (OS), and whether F FDG PET/CT could take the place of bone marrow biopsy (BMB). METHODS: The performance of F FDG PET/CT (BMPET) was evaluated. The prognostic value of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), stage, international prognostic index (IPI) score, IPI risk, lactate dehydrogenase (LDH), B2 microglobulin, Ki67 proliferation index, and the presence of BMI was evaluated for OS and PFS. Kaplan-Meier curves were drawn for each designated cutoff value, and 5-year PFS and 7-year OS were evaluated using log-rank analysis. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of BMPET and BMB to identify BMI were 69, 100, 86.1, 80, 100%, and 81.6, 100, 92.5, 89, 100%, respectively. The sensitivity, specificity, PPV, NPV, and accuracy of BMPET in patients with Ki67- proliferation index >25% were all 100%. BMPET, IPI risk, MTV, and LDH were found to be independent prognostic predictors for PFS, whereas BMPET, SUVmax, and MTV for OS. Five-year PFS analysis estimated as follows: BMPET (+) = 22%, BMPET (-) = 80%, LDH ≤ 437 (U/L) = 86%, LDH > 437 (U/L) = 51%, MTV ≤ 56 (cm) = 87%, MTV > 56 (cm) = 49%, low IPI risk = 87%, intermediate IPI risk = 69%, high IPI risk = 25%. Seven-year OS analysis was found as: SUVmax ≤ 17.6 = 80%, SUVmax > 17.6 = 48%, MTV ≤ 56 (cm) = 84.4%, MTV > 56 (cm) = 45.8%, BMPET (-) = 72.5%, BMPET (+) = 42%. CONCLUSION: In the Ki-67 proliferation index > 25% group, F FDG PET/CT was able to differentiate BMI independently from NHL subgroups. We recommend using this method with large patient groups. MTV and BMPET were independent prognostic indicators for OS and PFS and may help to determine high-risk patients.

Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcoma.

Leiomyosarcomas (LMS) are rare tumors with poor prognosis owing to the high rate of recurrent and metastatic disease. The combination of doxorubicin (Adriamycin) plus ifosfamide and mesna (AIM) results in moderate response rates of 10%-30%. The aim of this study was to assess the efficacy of the AIM regimen along with multimodality treatment including surgery and radiotherapy in patients with LMS. The clinicopathologic characteristics and outcomes of 51 patients with recurrent or metastatic LMS diagnosed between 2000 and 2014 who received the AIM regimen were analyzed retrospectively. Treatment consisted of ifosfamide 2500mg/m² on days 1-3 (with mesna 2500mg/m² days 1-3, 4-hour i.v. infusion), and doxorubicin 60mg/m² on day 1 (2-hour i.v. infusion), which was repeated every 21 days. The mean age of the patients at diagnosis was 48.9 ± 11.2 years. A total of 42 patients were females (82.4%). The primary tumor site was the uterus in 30 (58.8%) patients. The most common metastatic sites were lung and liver. The median follow-up was 27.9 months (min: 4.3 max: 164.8). The median progression-free survival was 6.7 months (95% CI: 4.1-9.2). The median overall survival (OS) was 24.6 months (95% CI: 16.2-33.0). The overall response rate was 12% (6/51 pts). Response rates were higher in patients with uterine LMS (17%) compared with those with nonuterine LMS (5%); however, the OS times were similar. Surgical intervention for local or distant recurrence was associated with improved median OS (41 vs 16.6 months, P < 0.001). Myelosuppression was the major toxicity of this combination. In our study, the AIM regimen was effective in patients with LMS. Resection of local or distant recurrence was found to improve survival in our study.

High complete remission rate and durable remissions achieved with rational use of autologous stem-cell transplantation, thalidomide maintenance, and non-myeloablative allogeneic transplantation in patients with multiple myeloma.

Autologous stem-cell transplantation (ASCT) has emerged as the standard approach in patients with multiple myeloma, although it is unlikely to achieve cure. Thalidomide maintenance and non-myeloablative allogeneic transplantation (NST) may increase complete remission (CR) rate and increase overall survival. In this study, 35 ASCT and 10 NST were performed in 33 patients. Patients, who were resistant or relapsed following ASCT, underwent NST if they had an HLA-matched sibling, otherwise treated with a second ASCT. Thalidomide was started as maintenance after ASCT. After first transplantation, three patients underwent second ASCT and 10 patients underwent NST. Following first transplantation, CR rate was 39% and increased to 60% (overall response 93%) with addition of thalidomide, bortezomib, and second transplantation. CR was durable in 14 (42%) patients. During a median follow-up of 24 months, 18 patients progressed and nine patients died. The 100-d transplant-related mortality was <5%. The four-yr progression-free survival (PFS) was 52.4%. In conclusion, ASCT followed by thalidomide and NST in resistant patients can lead to high CR and PFS rates. As a second transplantation has not been performed routinely, patients having durable CR had a chance to avoid or delay a second transplantation without compromising disease control.

Thymic epithelial neoplasia: a study of 58 cases.

Primary thymic epithelial neoplasms (PTENs) are uncommon tumors of anterior mediastinum with a broad range of biological characteristics. We retrospectively reviewed 58 consecutive patients with a diagnosis of PTENs that were confirmed pathologically during 28 yr. There were 58 patients, 31 males (53.4%) and 27 females (46.6%), with a mean age of 43.6 +/-13.8 yr (range, 17-73 yr). Twenty-one (36.2%) patients presented at the Masaoka stage I, 13 (22.4%) patient at stage II, 18 (31.0%) patient at stage III, and 6 (10.4%) patients at stage IV. Forty-five (77.7%) patients had myasthenia gravis, 1 (1.7%) immune deficiency, 1 (1.7%) pancytopenia, and 1 (1.7%) nephrotic syndrome. No paraneoplastic syndrome was associated in 10 (17.2%) patients. Complete resection was accomplished in 41 (70.7%) patients, while incomplete resection was performed in 8 (13.8%) patients. In nine (15.5%) patients only biopsy was carried out. Radiotherapy was administered to 19 (32.8%) patients. Eleven (19.0%) out of 58 who presented at advanced stages (at least III) received chemotherapy. Median follow-up period was 59 mo (range, 1-278 mo). During the follow-up period, 17 deaths occurred. Five patients (29.4%) died of tumor-related causes, and the remaining 12 patients died of other causes (cardiovascular diseases [n = 1, 5.9%], sepsis [n = 4, 23.5%], and MG-related respiratory insufficiency [n = 7, 41.2%]). The overall survival rates at 5 yr and 10 yr were 63.9% and 54.2%, respectively. Tumor-related survival rates at 5 yr and 10 yr were 89.0% and 83.2%, respectively. In our series, disease stage, presence or absence of myasthenia gravis, and tumor size did not affect survival (p> 0.05), either. Complete resection of the tumor seems to be the best predictive factor for long-term survival.

The role of Tc-99m (V) DMSA scintigraphy in the diagnosis and follow-up of lung cancer lesions.

OBJECTIVE: To define the role of Tc-99m (V) dimercaptosuccinic acid (DMSA) scanning in the detection of lung cancer (LC) and its metastases, and monitoring the response of LC lesions (LCL) to chemo/radiotherapy (TH). METHODS: Tc-99m (V) DMSA whole-body scans, planar thorax views, and thorax Single-photon emission computed tomography (SPECT) images were obtained both 30 min (early) and 5 h (late) after Tc-99m (V) DMSA administration in 12 small/nonsmall cell LC patients (11 men, 1 woman; mean age 59 years). Five patients also had bone scans. The same scintigraphic protocol was performed in 7 of 12 patients, 3 weeks after first-line TH. TH response was evaluated visually in all LCL and semiquantitatively in primary tumors (PT) of six patients, by comparing the tumor uptake ratios (TUR) of pre-TH and post-TH Tc-99m (V) DMSA SPECT [TUR = mean counts of region of interests (ROI) in PT/mean counts in contralateral ROI]. In seven patients, a 6-month survival was determined. RESULTS: Tc-99m (V) DMSA accumulated in 34 LCL (11 PT, 19 bone metastases, 1 suprarenal mass, 1 axillary node, 2 supraclavicular nodes). A total of 11 patients displayed Tc-99m (V) DMSA uptake in LCL and one patient did not show uptake. In six patients, SPECT imaging showed deeply located PT in the lung parenchyma better than planar views. In five patients, both planar and SPECT views revealed peripherally located PT in the lungs. Early scans showed 18 LCL and late scans displayed all the LCL. Nine bone metastases on pre-TH Tc-99m (V) DMSA scans revealed matched areas of increased Tc-99m methylene diphosphonate (MDP) uptake on bone scans; six bone metastases were additionally detected on Tc-99m (V) DMSA scans when compared with bone scans, and four bone metastases on Tc-99m (V) DMSA scans could not be compared with bone scans because bone scan was not performed. In one patient, Tc-99m (V) DMSA scans became positive for bone metastases on post-TH later than the bone scans for some of the bone metastases. Neither planar nor SPECT imaging showed mediastinal lesions defined on thorax CT in nine patients. On TH monitoring, 17 LCL showed diminished Tc-99m (V) DMSA uptake, one disappeared, four were unchanged, three displayed increased uptake, and five new lesions were established. Of the six patients, TUR in PT increased in two (one survived), decreased in one (exitus), was unchanged in two (two exitus) on post-TH scans, and PT totally disappeared in one (survived) patient. CONCLUSIONS: Tc-99m (V) DMSA scans are useful in detecting LCL, except for those around the blood pool regions, making it a promising modality to monitor TH response. Obtaining a single fifth hour late Tc-99m (V) DMSA scan is appropriate. SPECT should be applied to all patients for the detection of deeply located lesions.

Craniospinal radiotherapy in adult medulloblastoma.

PURPOSE: To evaluate the outcome and prognostic factors of adult patients with medulloblastoma. PATIENTS AND METHODS: 26 adult medulloblastoma patients with a median age of 27 were subjected to craniospinal radiotherapy. A dose of 30.6 Gy with 1.8 Gy/fraction/day was prescribed to M0 patients, while 36 Gy were to be applied in patients with positive cerebrospinal liquor findings. The posterior fossa was boosted to 54 Gy. While 20 patients underwent external-beam radiotheray alone, only six received sequential adjuvant chemotherapy. RESULTS: Male/female ratio was 1.2. Preradiotherapy Karnofsky performance status was recorded as median 100%. 50% were classified as poor risk (n = 10, subtotal resection; n = 3, M+). The median follow-up time was 46.5 months. The 5-year actuarial survival rates for recurrence-free, distant metastasis-free, disease-free, and overall survival were 82.5%, 90.8%, 73.5%, and 89.7%, respectively. Patient characteristics, treatment factors and tumor characteristics failed to show any significance in univariate analysis. Grade 3 or 4 late morbidities were not observed. CONCLUSION: Yet, the current standard of care seems to remain craniospinal irradiation after maximal surgical resection of the primary neoplasm without clear indications for adjuvant chemotherapy.

High dose sequential chemotherapy and autologous stem cell transplantation in patients with relapsed/refractory lymphoma.

Although high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard approach for patients with relapsed/refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), more than 50% of patients will experience relapse following ASCT. High-dose sequential chemotherapy (HDSC) can intensify the conventional salvage treatment and improve the outcome of ASCT by maximal debulking of the tumor load with the use of non-cross resistant drugs, each at their maximal tolerated doses. We conducted a phase II study in 40 patients with relapsed/refractory HD (n = 18) and NHL (n = 22) using HDSC followed by ASCT. Only patients sensitive to salvage chemotherapy were eligible for the protocol, consisting of three phases. Phase I consisted of cyclophosphamide (4.5 g/m2) followed by G-CSF and peripheral blood stem cell (PBSC) collection. Phase II consisted of etoposide (2 g/m2). The transplant phase consisted of mitoxantrone (60 mg/m2) and melphalan (180 mg/m2) followed by PBSC infusion. Eleven out of nineteen patients with B-cell lymphoma received rituximab. Prior to HDSC, 45% of the patients were in complete remission (CR) and 55% were in partial remission (PR). After completion of all phases of the protocol, 35 out of 39 evaluable patients achieved CR (90%) and this was durable in 30 (75%) patients with a projected progression-free survival (PFS) rate at 4 years of 71.7%. Treatment-related mortality rate at day +100 was 2.5% (n = 1). At a median follow-up of 32 months (range, 3 - 61), nine patients relapsed/progressed and eleven patients died. The estimated 4-year PFS and overall survival (OS) were 72.2% and 47.6% in HD patients and 70.3% and 69.4% in NHL patients, respectively. Factors predicting OS were response to conventional salvage therapy and stage prior to salvage therapy. When compared to patients achieving PR, patients who attained CR prior to HDSC had a significantly higher probability of 4-year OS (78.4% vs 31.3%, p = 0.02). Three prognostic subgroups were defined according to the score determined by stage prior to initiation of salvage chemotherapy, remission duration prior to salvage (refractory/early relapse vs. late relapse) and response to salvage. Prognostic score was found to predict OS, PFS and event free survival (EFS). In conclusion, HDSC followed by ASCT is an effective salvage therapy with acceptable toxicity, allowing further consolidation of response attained by conventional salvage therapy.

Ifosfamide, idarubicin, and etoposide in relapsed/refractory Hodgkin disease or non-Hodgkin lymphoma: a salvage regimen with high response rates before autologous stem cell transplantation.

To achieve long-term disease-free survival, high-dose therapy and autologous stem cell transplantation (ASCT) is the current standard approach in patients with relapsed or refractory Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL). Because chemosensitivity is a significant factor in determining transplantation eligibility, it is critical to select a salvage chemotherapy regimen that has the potential to induce a high response rate with low nonhematologic toxicity. In this phase II study, 49 patients with relapsed or refractory HD (n = 22) and NHL (n = 27) with a median age of 42 years were treated with an IIVP salvage regimen consisting of ifosfamide, idarubicin, and etoposide. Twenty-seven percent of the patients had primary refractory disease, whereas 22% and 51% had early and late relapses, respectively. As analyzed by intention to treat, 16 patients (33%) achieved complete remission and 21 patients (43%) achieved a partial response, leading to an overall response rate of 76% (63% in NHL and 91% in HD). In the univariate analysis, diagnosis (HD versus NHL), remission duration before the initiation of IIVP, disease bulk, increased lactate dehydrogenase, and the presence of "B" symptoms were significant factors affecting the response achieved by the IIVP regimen. Of 37 responders, 31 (84%) underwent high-dose therapy and transplantation. The probability of 4-year overall survival (OS) and event-free survival (EFS) in this group of patients who underwent ASCT was 67.7% and 49.1%, respectively. When compared with the patients who achieved a partial response, patients who achieved complete remission with the IIVP regimen had a significantly higher probability of 4-year EFS (67.3% versus 30%; P = .016) and 4-year OS (92.3% versus 39.2%; P = .003). In patients with HD, 4-year EFS and 4-year OS were 54.9% and 70.6%, respectively, without a significant difference with respect to the survival rates obtained in patients with NHL (43.6% and 63.6%, respectively). Common side effects observed during 102 cycles of therapy were grade 3 to 4 neutropenia (62%) and thrombocytopenia (58%). The IIVP regimen is a highly effective salvage regimen for patients with relapsed or refractory HD or NHL who are candidates for ASCT. Furthermore, the degree of response to IIVP predicts the posttransplantation outcome. However, close follow-up is necessary because of a high incidence of grade 3 to 4 hematologic toxicity.

IIVP salvage regimen induces high response rates in patients with relapsed lymphoma before autologous stem cell transplantation.

Patients with relapsed lymphoma can be cured with high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). New therapeutic approaches with better cytoreductive capacity are needed for relapsed patients to keep their chance for cure with transplantation. We report 30 patients with relapsed lymphoma, median age 43 years, treated with IIVP salvage regimen consisting of ifosfamide, mesna, idarubicin, and etoposide for 2 or 3 cycles. Seventeen patients had non-Hodgkin lymphoma (NHL) and 13 patients had Hodgkin disease (HD). Fourteen (47%) patients were at their first relapse. Overall response rate was 86.6% (n = 26) with 19 patients (63.3%) achieving complete response. Overall response rate was 92% in patients with HD and 82% in NHL. The most frequent side effects observed were grade III-IV neutropenia (87%) and thrombocytopenia (73%). IIVP regimen is a highly effective salvage therapy for patients with relapsed HD or NHL who are candidates for autologous HSCT. Close follow up is necessary because of the high incidence of grade III-IV hematologic toxicity.