Role Of High-dose Chemotherapy Research Articles

The Role of High Dose Chemotherapy with Autologous Hematopoietic Cell Transplant in Relapsed/Refractory Ovarian Germ Cell Tumors: A Single Center Experience

ObjectiveWe aimed to investigate response rates, survival analyses and factors affecting survival in patients with relapsed or refractory ovarian germ cell tumours who had previously received multiple lines of treatment, including high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT). MethodsThis study was designed as a cross-sectional, retrospective study. ResultsTwenty-one patients were included. After HDC + ASCT, complete response (CR) was observed in 11 patients (52.3%), partial response (PR) in 3 patients (14.3%), stable disease (SD) in 3 patients (14.3%) and progressive disease (PD) in 4 patients (19.1%). TRM was observed in 1 patient. Median follow-up was 51.7 months. Median PFS and OS after HDC + ASCT were calculated to be 6.0 months and 14.8 months, respectively. ConclusionsSalvage HDC + ASCT is an effective option in the treatment of relapsed/refractory ovarian germ cell tumours, offering the potential for prolonged survival and cure.

Consensus recommendations in the management of Ewing sarcoma from the National Ewing Sarcoma Tumor Board.

Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. Despite an international coordinated approach, several nuances, discrepancies, and debates remain in defining the standard of care for treating ES. In this review, the authors leverage the expertise assembled by formation of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of ES. This report is focused on select topics that apply to the management of patients with newly diagnosed ES. The specific topics covered include indications for bone marrow aspirate and biopsy for initial evaluation compared with fluorodeoxyglucose-positron emission tomography, the role of interval compressed chemotherapy in patients aged 18years and older, the role of adding ifosfamide/etoposide to vincristine/doxorubicin/cyclophosphamide for patients with metastatic disease, the data on and role of high-dose chemotherapy with autologous stem cell transplantation, maintenance therapy, and whole-lung irradiation. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, the guidelines are intended to provide clarity and recommendations for the upfront management of patients with ES. PLAIN LANGUAGE SUMMARY: Ewing sarcoma is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. For this review, the authors used the experience of the National Ewing Sarcoma Tumor Board, a multi-institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of Ewing sarcoma. Although not intended to replace the clinical judgement of treating physicians, the guidelines will focus on the development of consensus statements for the upfront management of patients with Ewing sarcoma.

Safety and efficacy of autologous stem cell transplantation in dialysis-dependent myeloma patients-The DIADEM study from the chronic malignancies working party of the EBMT.

The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.

Favorable outcome of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with nonmetastatic osteosarcoma and low-degree necrosis.

BackgroundA low-degree tumor necrosis after neoadjuvant chemotherapy is a poor prognostic factor for osteosarcoma (OSA). However, the role of high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation in OSA remains controversial. We analyzed the treatment outcomes and prognostic factors of nonmetastatic OSA and compared the HDC and conventional chemotherapy (CC) outcomes of patients with <90% necrosis after neoadjuvant chemotherapy.MethodsWe retrospectively evaluated patients with OSA treated at the Seoul National University Children’s Hospital from 2000 to 2020. Totally, 113 patients with non-metastatic OSA at diagnosis were included. The majority were treated with cisplatin, doxorubicin, and methotrexate as neoadjuvant chemotherapy. This was continued when the postoperative necrosis rate was >90% (good response [GR]), whereas most cases with <90% (poor response [PR]) were changed to chemotherapy. The HDC regimen was composed of melphalan, etoposide, and carboplatin.ResultsThe median age at diagnosis was 12.6 years (range, 5.0–20.3), and 61.9% of patients were men. The 5-year event-free survival (EFS) and overall survival (OS) rates were 75.8% and 91.5%, respectively. Among these, 59 and 44 patients were included in the GR and PR groups, respectively. The GR group had a better 5-year EFS rate than the PR group (82.4% vs. 67.3%, p=0.071). Age at diagnosis, sex, tumor site, type of neoadjuvant chemotherapy, and degree of tumor necrosis were not different between the PR-HDC (n=24) and PR-CC (n=20) groups. The 5-year EFS and OS rates in the PR-HDC (n=24) and PR-CC (n=20) groups were 78.6% and 53.6% (p=0.065) and 100% and 76.9% (p=0.024), respectively. In the Cox regression analysis, the PR-CC group (hazard ratio, 4.95; p=0.004) and age ≥12 years (hazard ratio, 2.68; p=0.024) were significant risk factors for 5-year EFS.ConclusionsHDC showed favorable outcomes in patients with non-metastatic OSA and <90% necrosis after neoadjuvant chemotherapy.

The role of high-dose chemotherapy with autologous stem cell transplantation in adults with mature T-cell lymphomas

The role of high-dose chemotherapy with autologous stem cell transplantation in adults with mature T-cell lymphomas

Current treatments of medulloblastoma.

The biological knowledge and the new biopathological classification of medulloblastoma subtypes have dramatically changed the therapeutic indications, taking into account not only age and staging but also biopathological risk criteria. This review covers the multidisciplinary approach including surgery, radiation oncology and medical treatments. The neurosurgical management of tumor-related hydrocephalus has been modified by the introduction of third ventriculostomy. The initial complete excision is no longer always the first choice, to preserve neurological function. The recent technical improvements of radiotherapy are also implemented to optimize outcome in terms of survival as well as quality of survival. The different medical treatments are adapted according to age and risk factors. The role of high-dose chemotherapy with autologous hematopoietic stem cell rescue has become larger in the high-risk situations. The rarity of the disease and the high-level of technicity of diagnosis, biopathological subtyping and treatments justifies the referral of these patients to highly specialized centers where all these techniques can be routinely applied, most often in the context of international prospective studies.

Role of High Dose Chemotherapy and Autologous Stem Cell Transplant in Relapsed Ewing's Sarcoma — a Systematic Review

Introduction: Relapsed Ewing's sarcoma (ES) is an aggressive malignancy with poor survival. Conventional dose salvage chemotherapy (CC) regimens given at the time of relapse led to response rate up to 28-68% with reported event free survival (EFS) of 29% at 2 years and Overall survival (OS) of 49 % at 1 year and 28-31 % at 2 years (Van Winkle, P. et al. 2005, Magnan et al. 2015). High dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) given as induction or as part of consolidation treatment after few cycles of CC has shown benefit in improving OS and EFS in single center studies. (McTiernan et al. 2006, Barker et al. 2005) Despite report of its utility, HDCT is not generally used in United states for relapsed ES and a comprehensive search and systemic review was performed to evaluate the benefits of HDCT for this disease.Methods: Comprehensive literature search was conducted in Medline (PubMed and Ovid SP), Embase and Cochrane Database of Systematic Review (CDSR). These databases were searched from the inception of databases till present. In addition, we manually selected more studies from bibliography data. We included studies that had relapsed Ewing's sarcoma patients and those which had mixed data for relapsed as well as primary metastatic disease treated with HDCT.Results: Through literature and bibliography search, 1005 studies were identified and after screening, 24 studies containing a total of 1459 patients were included in the final analysis. Seventeen studies had patients with primary metastatic disease and relapsed Ewing's sarcoma. Seven had only relapsed ES patients. In the studies with relapsed patients (n = 809), EFS for most studies at two and five years ranged from 42-44% and 24-43% respectively. The OS at two years and three to five years ranged from 50-66% and 21-50% respectively. In studies with combined primary metastatic and relapsed patients (n=650), EFS at one to two years and three to five years was 45-60% and 17-47% respectively. The OS at one to two years and three to five years was 40-70% and 31-50% respectively.Five studies (n=709) (Table 1) compared results of patients who received HDCT along with ASCT after CC to those who received only CC. Two to three and four to five years EFS for patients who received HDCT was 39-44% and 17-61% respectively, whereas it was 10-32% and 2-7% for patients who received only conventional dose therapy. OS of patients who received HDCT was 50-66% at two to three years and 42-77% at four to five years, whereas it was 14-34% and 7-10% respectively for patients who received only CC. Patients selected to receive HDCT in most of these studies were those who showed a response to initial CC (chemosensitive), either complete or partial response (CR/PR) (Rasper et al. 2014, Dirkson et al. 2014, Barker et al. 2005, Al faris et al. 2007, Frolich et al. 1999).Relapsed patients in Pole et al. (1984) survived only for three to six months. They had metastatic disease at relapse and did not receive conventional therapy prior to HDCT, possibly contributing to their decreased survival. Shankar et al 2003 reported EFS and OS at three and half years to be 14% and 28% respectively in spite of receiving CC followed by HDCT and ASCT.Conclusions: Most studies showed that HDCT followed by ASCT given as consolidation regimen improved OS and EFS compared to CC. Two studies (Pole et al. 1984 and Shankar et al. 2003) showed lower survival after HDCT when compared to CC. Patients in Pole et al study had metastatic disease at relapse and also did not receive CC prior to HDCT, which may have affected the survival. The reason for decreased survival in Shankar et al study is not clear. Five studies which compared patients who received HDCT and ASCT in addition to CC with patients who received only CC showed improved survival in patients who received HDCT followed by ASCT. Patients selected to receive HDCT showed initial chemosensitivity (by achieving CR or PR) to CC, suggesting that proof of chemosensitive disease is an important prognostic factor for improving survival with HDCT. The heterogeneity in the data prevented us from conducting a meta-analysis. Large scale randomized control studies are needed to determine true clinical benefit of HDCT followed by ASCT in patients with relapsed Ewing's sarcoma. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Treatment Strategies for Children With Relapsed Pancreatoblastoma: A Literature Review.

Pancreatoblastoma (PB) is a tumor typically seen in childhood. Despite its rarity, there are some internationally agreed recommendations for its first-line treatment, but very little is known about the management of relapse. We reviewed the literature on the treatment and outcome of children with progressing/recurrent PB, and the role of high-dose chemotherapy (HD-CT) or liver transplantation in difficult cases. A first analysis concerned 15 patients: liver metastases were the most frequent cause of first-line treatment failure. Eight patients underwent surgery, only 3 were irradiated. Various second-line chemotherapy regimens were adopted, with evidence of response in 8 children. The most often-used combinations included etoposide, cyclophosphamide/ifosfamide, and cisplatin/carboplatin. Overall, 7 patients are alive with a median follow-up of 24 months (range, 3 to 88 mo). In a separate analysis, considering patients in first-line or second-line treatment, we found 5 of 6 patients alive after HD-CT and 3 of 3 after liver transplantation. Our review shows that the outcome for patients with recurrent PB is not always dismal, especially when surgery is possible. Different chemotherapy combinations can be used, and HD-CT or liver transplantation may be considered in selected cases.

Treatment Strategies and Outcomes for Patients with Peripheral T-Cell Lymphoma and Its Subtypes

Introduction Peripheral T-cell lymphoma (PTCL) is diverse group of an uncommon and aggressive type of non-Hodgkin lymphoma (NHL). It generally affects people aged 60 years and above and is diagnosed slightly more often in men than in women. However, younger adults and children are also diagnosed with PTCL. Being a rare entity, the best treatment regimen has not been established for newly diagnosed patients or for relapsed/refractory patients with PTCL. In general, treatment outcomes have been poor with conventional chemotherapy regimens. Methods We performed a retrospective cohort study of patients with newly diagnosed and relapsed PTCL, and its subtypes, who are seen in the hematology-oncology clinic at the University of Arkansas for Medical Sciences from July 2014 to December 2019. The demographics of the study population, the frontline and second-line treatment strategies for all the subtypes and the response to the treatment were studied. Also, the role of high dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) in the overall survival (OS) and progression-free survival (PFS) is analyzed. Results Out of the 48 patients, 45.8% (n=22) patients had PTCL not otherwise specified (PTCL NOS) type, 29% (n=14) had Anaplastic large cell lymphoma ALK-negative subtype, 4.2 % (n=2) had Anaplastic large cell lymphoma ALK-positive subtype, Angioimmunoblastic T-cell lymphoma, Extra nodal NK/T cell lymphoma, Enteropathy associated T- cell lymphoma each. The mean age of diagnosis was 58 ± 2. Males were affected more when compared to females (66.6% vs 33.3%). Also, Caucasians were more affected than African Americans (73% vs 25%). The mortality of PTCL was found to be 40%. After frontline treatment, complete response (CR) was observed in 43.7% (n= 21) patients, partial response (PR) was observed in 18.7% (n= 9) patients, stable disease (SD) was seen in 4% (n=2), progression of disease (PD) was observed in 12.5% (n= 6) patients. Stem cell transplant (HDT-ASCT) was done for 28% (n=13) of patients who achieved CR after frontline chemotherapy (CR1). Relapse was observed in 60% of patients. Patients with stage III and IV on the initial diagnosis had a higher chance of relapse or refractory disease. After the second-line treatment, out of 20 patients, 9 patients had CR, 5 had PR, 5 patients had PD, 1 patient had SD. CR was observed in 7 patients with either brentuximab vedotin alone or brentuximab vedotin with combination chemotherapy as second-line treatment. The OS and PFS were found to be higher in patients who received HDT-ASCT after CR1. Conclusion PTCL has a high risk of relapse and there are no uniform guidelines for the treatment of PTCL in relapsed or refractory setting. The currently available second line treatment options have shown modest response rates. Our study has shown that brentuximab vedotin, when used alone or in combination, showed better response rate in the relapsed setting. Also, stem cell transplant improved the overall survival and progression-free survival in patients with PTCL after frontline chemotherapy. Disclosures No relevant conflicts of interest to declare.

État des lieux de la chimiothérapie intensive avec support de cellules-souches hématopoïétiques dans le traitement des tumeurs germinales

More than 80 % of patient with metastatic germ cell tumor are cured with first line chemotherapy. Twenty to 30 % of patients will experience relapse or refractory disease with a very poor long-term prognosis. Most of them had metastatic germ cell tumors with a poor prognosis according to the international germ cell classification collaborative group (IGCCCG). The role of treatment intensification by high dose chemotherapy (HDCT) followed by stem cell rescue has not been demonstrated yet in the first line setting compared to standard chemotherapy. The role of HDCT in first or second salvage is also not yet demonstrated, many studies have been published in this situation with a lot of different regimen. Outside clinical trial, HDCT remains an option in salvage therapy, depending on many factors including prognostics factors, previous therapy, general condition and reference center consideration to select eligible patient who could benefit the most of this approach. Results from the international randomized trial TIGER will provide evidence-based information for HDCT strategy.

Should the emphasis be on induction or consolidation therapy in transplant-eligible, newly diagnosed multiple myeloma?

Department of Hematology and Hematopoietic Transplantation, City of Hope National Medical Center, Duarte, CA, USA [email protected] Autologous haematopoietic stem-cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 studyThis study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. Full-Text PDF

Very long term follow-up of high dose chemotherapy followed by autologous stem cell transplantation in high risk locally advanced triple negative breast cancer.

e13094 Background: The role of High Dose Chemotherapy (HDC) with Autologous Stem Cell Transplantation (ASCT) in treatment of high risk locally advanced breast cancer remains unclear. This modality stopped being used for breast cancer treatment when trials in early 2000s reported Disease Free Survival (DFS) benefit but no Overall survival (OS) benefit. However, subgroup analyses of these studies reported OS benefit in young and Triple Negative Breast Cancer (TNBC). We report very long-term outcomes of high risk locally advanced TNBC treated with HDC-ASCT at our institution between 1995 and 2001. Methods: We reviewed our BMT database for women with stage IIB or III TNBC treated with HDC-ASCT. We excluded women with hormone positive, Her2/Neu positive/Unknown and metastatic disease prior to transplant per updated AJCC 7th edition. The majority of patients underwent surgery followed by adjuvant Anthracycline and Taxane based induction chemotherapy followed by HDC-ASCT for consolidation. The HDC regimen consisted of Carmustine 600 mg/m2, Cyclophosphamide 5.6gm/ m2 and Cisplatin 165mg/ m2 (STAMP 1 regimen). Four patients received induction regimen as neoadjuvant and HDC-ASCT as adjuvant treatment per the same protocol. All patients received loco-regional radiation after ASCT. Results: 29 patients had locally advanced TNBC treated with HDC-ASCT. Median age at diagnosis was 43 years (IQR 40-51). 28 had at least 4 positive lymph nodes. Median time from diagnosis to ASCT was 5 months. Median overall survival was 17 years (95% CI, 3-19 years), and median DFS was 14 years (95% CI, 1-19). There was no treatment related mortality (TRM) at 30- and 100-days post ASCT. 12 patients (41%) were alive at median of 16 years (95% CI, 12-19) post ASCT. Conclusions: This single institution study of locally advanced high risk TNBC patients who received HDC-ASCT as part of treatment demonstrates a high long term OS exceeded historical controls. This supports a potential role for HDC-ASCT in this cohort of high risk TNBC. Considering the low TRM associated with this approach, prospective evaluation of this strategy is warranted.

Role of high-dose chemotherapy with autologous stem cell transplantation for primary central nervous system lymphoma: A systematic review.

2562 Background: High dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) has shown to overcome intrinsic chemo-resistance and improve disease control in Primary Central Nervous System Lymphoma (PCNSL). Our study reviews the treatment outcome in PCNSL with sequential HDCT and ASCT. Methods: 8/34 studies were finalized after systematic search of PubMed, Cochrane, and Clinicaltrials.gov for treatment of PCNSL with HDCT followed by ASCT. Results: 251/288 patients were evaluated. Mean age was 55.5 years. 227 underwent HDCT-ASCT. 174 were newly diagnosed (ND) and 77 had relapsed refractory (R/R) PCNSL. ND patients showed superior outcomes in terms of progression free survival and overall survival. Combinations of High dose Rituximab, Busulfan and Cyclophosphamide significantly improved survival outcomes in RR patients. Significant toxicities mainly included pancytopenias and opportunistic. Conclusions: Primary CNS lymphoma treated with HDCT followed by ASCT has shown promising outcomes and has set a benchmark for future studies. [Table: see text]

Autologous haematopoietic stem-cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study

The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation. In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m2 administered orally on days 1-4) and prednisone (60 mg/m2 administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m2), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m2 either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2-67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3-64·5] vs 41·9 months [37·5-46·9]; hazard ratio [HR] 0·73, 0·62-0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3-49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0-not estimable] vs 45·5 months [39·5-58·4]; HR 0·77, 0·63-0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. Janssen and Celgene.

CD38: A Target for Immunotherapeutic Approaches in Multiple Myeloma.

Multiple Myeloma (MM) is a hematological cancer characterized by proliferation of malignant plasma cells in the bone marrow (BM). MM represents the second most frequent hematological malignancy, accounting 1% of all cancer and 13% of hematological tumors, with ~9,000 new cases per year. Patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic smoldering MM (SMM) usually evolve to active MM in the presence of increased tumor burden, symptoms and organ damage. Despite the role of high dose chemotherapy in combination with autologous stem cell transplantation and the introduction of new treatments, the prognosis of MM patients is still poor, and novel therapeutic approaches have been tested in the last years, including new immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies (mAbs). CD38 is a glycoprotein with ectoenzymatic functions, which is expressed on plasma cells and other lymphoid and myeloid cell populations. Since its expression is very high and uniform on myeloma cells, CD38 is a good target for novel therapeutic strategies. Among them, immunotherapy represents a promising approach. Here, we summarized recent findings regarding CD38-targeted immunotherapy of MM in pre-clinical models and clinical trials, including (i) mAbs (daratumumab and isatuximab), (ii) radioimmunotherapy, and (iii) adoptive cell therapy, using chimeric antigen receptor (CAR)-transfected T cells specific for CD38. Finally, we discussed the efficacy and possible limitations of these therapeutic approaches for MM patients.

Role of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for Children and Young Adults with Relapsed Ewing’s Sarcoma: A Systematic Review

Background Relapsed Ewing's sarcoma (RES) is an aggressive malignancy with poor survival. Although high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) given after conventional chemotherapy (CC) has shown survival benefits, it is not generally used in the United States for RES. We performed a systemic review to evaluate the benefits of HDCT for RES. Methods Literature search involved Medline, Embase, and Cochrane database. We included studies with RES patients treated with HDCT/ASCT. Results Twenty-four studies with total of 345 reported RES patients that got HDCT were included in final analysis. Seventeen studies had patients with multiple malignancies including RES, while seven had only RES patients. At 2 and 3–5 years, event-free survival (EFS) in studies with only RES patients ranged 42–47% and 20–61% and overall survival (OS) ranged 50–66% and 33–77%, respectively. In studies with combined patients that reported outcomes of RES separately, the EFS at 1–3 and 4 years was 36–66% and 17–50%, respectively. The OS at 1-2 and 3-4 years was 40–60% and 50–70%. Conclusions Most studies using HDCT/ASCT as consolidation regimen showed improved survival benefits compared to CC. Randomized controlled studies are needed to determine true clinical benefits of HDCT followed by ASCT in patients with RES.

The role of high-dose chemotherapy (CT) and stem-cell support in high-risk stage II, locally advanced, and responding stage IV breast cancer (BC): The Israeli experience with 20 years median follow-up.

1077 Background: Lately, updated data led the medical community to reconsider the use of intensive CT with stem-cell support for selected groups of BC patients (pts). Herein, we provide an update on a study investigating the efficacy, feasibility, and toxicity of high-dose CT with stem-cell support in pts with high-risk stage II, chemosensitive stage III and IV BC. Methods: The protocol offered adjuvant/neoadjuvant/induction doxorubicin-based CT, 75-90 mg/m2 X 4 courses followed by high-dose CT (cyclophosphamide 6000 mg/m2, carboplatin 800 mg/m2, and thiotepa 500 mg/m2) and autologous stem cell support with growth factors. Post-transplant local radiotherapy was delivered. Pts who were hormone receptor (HR) positive received Tamoxifen. Results: From 2/1994 to 11/1998, 292 BC pts were referred to the study from all Israeli oncology centers. Median follow-up from transplant was 20 (range, 18-22) years; 119 had stage 2 disease (42 with 4-9 positive nodes, 77 with ≥10 positive nodes); 87 had stage 3 disease, of whom 50 had locally advanced/inflammatory BC treated with neoadjuvant CT; and 86 had chemosensitive stage IV BC. Two acute transplant-related deaths and one death due to late transplant-related toxicity were reported. Median age at transplant was 45 (range, 24-63) years. Overall survival (OS) by HR status is presented in the table. In total, 167 of the 292 pts died (based on death status data retrieved from the Registry of the Ministry of the Interior), representing OS of 42%. The OS rates for stage II, III, and IV were 55%, 45%, and 23%, respectively. Conclusions: Long-term accurate follow-up of pts receiving well-defined treatments remains an important tool in cancer research. High-dose CT with stem-cell support could represent a therapeutic/curative option in select BC patients in all disease stages. Reintroduction of this approach should be re-examined. [Table: see text]

A Review of Ewing Sarcoma Treatment: Is it Still a Subject of Debate?

The Ewing sarcoma (ES) represents 10 to 15% malignant bone tumors and 40 to 45% pediatric malignant bone tumors. The aim of this review is to clarify the therapeutic results and prognostic factors of this entity. A systematic review of the literature was performed. Studies focused on the management of ES were considered for inclusion. ES represents a model of multidisciplinary approach. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between the pediatric and medical oncologists. The overall 5- year survival of Ewing localized tumors was 70% versus 30% in metastatic ES. The treatment of ES includes neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The role of high-dose chemotherapy is still debated.

Role of Consolidation High Dose Chemotherapy (HDC) with Autologous Stem Cell Transplant (ASCT) Support in Patients with Peripheral T-Cell Lymphoma Who Achieved Complete Remission (CR1) Following First Line Induction Chemotherapy

Background: Peripheral T-cell lymphomas (PTCL) typically have a dismal outcome when treated with conventional combination chemotherapy. However, the role of HDC with ASCT in patients who attained CR1 following induction chemotherapy remains controversial.Methods: This is a retrospective analysis performed using a prospective database of newly diagnosed PTCL patients treated at our centres from 1993 to 2015. After excluding patients with NK/T cell lymphoma, ALK-positive anaplastic large cell lymphoma, cutaneous T cell lymphoma and composite lymphomas, we identified 164 PTCL patients who were treated with curative intent. Among them, 73 patients achieved CR1 following induction chemotherapy. We compared the characteristics and outcomes of those who went on to receive further ASCT with those who did not receive further consolidation ASCT. Fisher's exact test and Student's T test was used to compare the baseline characteristics such as age, stage, international prognostic index risk group (IPI), prognostic index for PTCL (PIT), lactate dehydrogenase (LDH) and treatments between the two cohorts. Progression-free survival (PFS) and overall survival (OS) were compared using the log-rank test. Cox proportional hazard regression analysis was performed to estimate the hazard ratios (HR).Results: Of the 164 patients treated with curative intent, the median OS of patients who achieved CR1 was not reached compared to 1.23 years among those who did not achieve CR1 with a HR of 5.24 (95% CI: 3.11-8.83, p<0.0001). The median age of the 73 PTCL patients who attained CR1 was 54 years (range: 18-76). Among them, 37% had stage I-II disease, 63% had III-IV disease, 25% had bone marrow involvement and 64% had elevated LDH. Majority of the patients (77%) received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy. Of the 73 patients who attained CR1 following induction chemotherapy, 16 (22%) received ASCT in CR1 while 57 (78%) received no further treatment. The baseline characteristics between these two cohorts were balanced except for age group and IPI. The median age of patients who had ASCT was 48.5 years (range: 18-63) compared to 56 years (range: 26-76) among those who did not undergo ASCT (p=0.0146). Although more patients in the non-transplanted group had higher IPI scores compared to the transplanted group, the distribution of patients across PIT risk groups was comparable (Table 1). The median OS of patients who underwent ASCT was not reached compared to 12.01 years in patients treated with conventional chemotherapy alone with a HR of 6.35 (95% CI: 0.77-52.56, p=0.09) after adjusting for age and IPI. The median PFS of patients who underwent ASCT was not reached compared to 5.18 years in conventionally treated patients with a HR of 2.33 (95% CI: 0.80-6.75, p=0.12) after adjusting for age and IPI.Conclusion: In this retrospective study of patients with PTCL in CR1, after adjusting for age and IPI, the OS and PFS of patients who underwent ASCT do not appear to be statistically different from those who received conventional chemotherapy alone. The study suggests that patients who achieved CR1 may have tumors that are inherently biologically favorable and further consolidation therapy may not be needed, at least not for all patients. Further study is warranted to establish the true benefit of ASCT in PTCL patients achieving CR1. Uncovering the genetic differences between responders and poor responders may identify new targets for PTCL. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

High Dose Chemotherapy with Autologous Stem Cell Transplant in Treatment of Germ Cell Tumors: A Systematic Review and Meta-Analysis

Background:Cure rates for the poor risk, relapsed and refractory germ cell tumors are only 25 % with conventional dose chemotherapy. High Dose Chemotherapy (HDCT) followed by rescue stem cell transplant has since been studied in randomized controlled trails for the IGCCG poor risk group patients and for the relapsed and refractory testicular cancer patients. We conducted a meta-analysis of all prospective Phase II and III trials studying the role of high dose chemotherapy in germ cell tumors.Methods:Literature search was conducted using methods described in the PRISMA statement. Medline (PubMed and Ovid SP), Embase, Cochrane Central Register of Controlled Clinical Trials(CENTRAL) and Cochrane Database of Systematic Review (CDSR) were searched from the inception of these databases till present. We performed a meta-analysis using Comprehensive Meta-analysis 3.0 using random effects model. The heterogeneity was assessed using I2values and sensitivity analysis was performed to explain the heterogeneity where present.Results:After a comprehensive literature search 4440 studies were identified and finally 35 studies were included in the final analysis. 14 studies involving 905 patients with IGCCG poor risk germ cell cancer were treated with high dose chemotherapy. 44 % (398) patients were able to achieve CR with HDCT with HR of o.48 (0.33-0.62) p=0.75. The overall survival (OS) and Progression free survival (PFS ) were 0.62 (0.54-0.69, p=0.004) and 0.60 (0.52-0.68 p=0.011) respectively.21 studies involving 1153 patients with relapsed and or refractory germ cell cancer were identified. CR rate with HDCT was 32 % (374 patients) with HR of 0.32 (0.26-0.40, p=0.00). The results for OS failed to show any significant results with HR of 0.52 (0.44-0.60, p=0.67) but was significant for PFS with HR of 0.60 (0.52-0.67, p=0.01).Conclusion:High dose chemotherapy followed by HSCT showed significant OS and PFS for IGCCG poor risk category germ cell tumors and significant CR and PFS for relapsed and or refractory germ cell cancer group. DisclosuresAnwer:Incyte: Speakers Bureau; Seattle Genetics: Other: Advisory Board Participant.