Autologous Stem Cell Transplantation In Patients Research Articles

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.

Application of the Conditioning Regimen with Busulfan and Cyclophosphamide in Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Backgroud Busulfan isthe most commonly used drug in conditioning regimens for hematopoietic stem cell transplantation, and high-dose melphalan (HDM)is the standard conditioning regimen in autologous stem cell transplantation(ASCT)for multiple myeloma. Studies have shown that in ASCT for multiple myeloma, conditioning regimens containing busulfan is equally effective as HDM.Aims Evaluate the safety and efficacy of BUCY(busulfan and cyclophosphamide ) conditioning regimen for autologous hematopoietic stem cell transplantation(ASCT)in patients with multiple myeloma(MM).Methods We retrospectively analyzed the clinical data of 72 MM patients who received transplantation in the Hematology Department of the First People's Hospital of Soochow University from May 2012 to June 2015. Among them, 36 patients underwent BUCY regimen, while the others received HDM regimen. Those were compared between the two groups including the complication, the hematopoietic reconstitution and the post-transplantation efficacy.Results There were no significant differences in age, stage, induction therapy, mobilization method between the two groups. The transplantation-related adverse events were similar in both groups but the incidence of pulmonary infection and bloodstream infection were slightly higher in BUCY group .The median time to neutrophil engraftment in the BUCY and HDM groups were 10(8-17)days versus 10(9-13)days, taking the same time on average(P=0.046). On the other hand, the median time to platelet engraftment was 10(8-18)versus 11(9-47)days accordingly (P=0.017). The TRM in both group was 2.7%. The SCR/CR rates after ASCT (47.2% and 50.0%) were higher than those before it (38.9% and 26.6%) in both groups. In the BUCY group, the median follow-up was 12.5(0-26) months. Six patients (16.7%) underwent disease progression. The 2-year progression-free survival(PFS) rate was 68%. Correspondingly, in the HDM group, the median follow-up time was 23 (0-38) months. Fifteen patients (41.7%) developed disease progression and the 2-year PFS rate was 55%.Conclusion The BUCY regimen is a safe and effective therapy for ASCT in patients with multiple myeloma. Besides, BUCY regimen is not inferior to HDM regimen. In conclusion, BUCY regimen may replace HDM regimen as a standard conditioning regimen for ASCT in multiple myeloma. DisclosuresNo relevant conflicts of interest to declare.

Indications for Hematopoietic Stem Cell Transplantation in Patients with Waldenstrom's Macroglobulinemia: A Consensus Project of the EBMT Lymphoma Working Party (LWP)/ European Consortium for Waldenstrom's Macroglobulinemia (ECWM)/International Waldenstrom's Macroglobulinemia Foundation (IWMF)

Indications for Hematopoietic Stem Cell Transplantation in Patients with Waldenstrom's Macroglobulinemia: A Consensus Project of the EBMT Lymphoma Working Party (LWP)/ European Consortium for Waldenstrom's Macroglobulinemia (ECWM)/International Waldenstrom's Macroglobulinemia Foundation (IWMF)

Melphalan Dose in Myeloma Patients over 65 Years of Age Undergoing High-Dose Therapy and Autologous Stem Cell Transplantation

IntroductionConsolidating high-dose chemotherapy with melphalan followed by autologous stem cell transplantation (ASCT) is believed to be superior to conventional chemotherapy alone in fit multiple myeloma patients ≥65 years. However, contemporary high quality data on the overall efficacy and safety of ASCT in this elderly age group are missing, and the conditioning regimen including the optimal melphalan dose is a matter of debate. Our present study aims at addressing the issue of the melphalan dosing prior to ASCT in patients ≥ 65 years of age.MethodsThis is an observational, multi-center, non-interventional research project based on data of the prospective Swiss Blood Stem Cell Transplantation Registry. Included are all Swiss patients ≥65 years with multiple myeloma who received high-dose chemotherapy followed by ASCT. Patients receiving melphalan at a dose of 200mg/sqm, and patients receiving melphalan at a dose of < 200mg/sqm were analyzed separately. For the 53 patients receiving double ASCT, only the first ASCT was considered, and survival was censored at the time of second ASCT. The main outcomes analyzed in the study were treatment-related mortality prior to day 100 (TRM), progression free survival (PFS), and overall survival (OS) estimates at two and five years.ResultsBetween 2000 and 2016, 414 patients with multiple myeloma aged 65 years and older received high-dose chemotherapy with melphalan and ASCT. Of those, 165 patients (40%) were female. The median age at ASCT was 67 years (range 65-77 years), and the median observation time of the surviving patients was 19 (range 0-215) months. Monoclonal component subtype was IgG (n=247, 60%), IgA (n=90, 22%), light chain (n=65, 16%), and others (n=12, 2%), respectively. Risk stratification according to the International Staging System (ISS) defined stage I in 136 (38.1%) patients, stage II in 144 (40.3%) patients, and stage III in 77 (21.6%) patients. Cytogenetic information was available for 212 (51.2%) patients, with 44 (20.8%) patients presenting high-risk features defined by the presence of del(17p), t(4;14), t(14;16), or combinations of these. Remission status prior to transplant was complete response (n=50, 12%), very good partial response (n=105, 25%), and partial response (n=229, 55%), respectively. Most patients had a Karnofsky Performance Status (KPS) of 90-100% prior to ASCT (n=318, 80.3%), while a KPS ≤ 80% was observed in 78 (19.7%) patients. Two hundred ninety-one patients (70%) received a melphalan dose of 200mg/sqm, and 123 patients (30%) received less than 200mg/sqm (median 140mg/msq, range 70 to 180mg/sqm). Patients who received melphalan doses <200mg/sqm were slightly older (67.8 years vs. 67.3 years, p=0.004), and had higher serum creatinine levels (80 µmol/l vs. 74 µmol/l, p<0.001), but did not differ with regards to ISS stage, cytogenetic risk group, remission status, and KPS prior to ASCT. At day 100, seven patients (1.7%) had died due to transplant-related complications, without differences between the two melphalan dose groups (p=0.429). Median PFS in the melphalan 200mg/sqm group was 25.9 months (21.1-30.7 months), and in patients receiving lower melphalan doses 25.2 months (17.9-32.5 months), respectively (p=0.656) (Figure1A). Estimated overall survival at 2 years and 5 years were 84.1% (79.0-89.2%), and 60.2% (51.4-69.0%) in the melphalan 200mg/sqm group, as compared to 85.1% (77.6-92.5%) and 56.0% (40.5-71.5%) in patients receiving lower melphalan doses (p=0.701) (Figure 1B). In a multivariate analysis adjusted for renal function, ISS stage, age at ASCT, and KPS, the melphalan dose was not associated with differences in the PFS or the OS.ConclusionsThe present study shows that high-dose melphalan and ASCT is feasible and safe in an elderly patient population with multiple myeloma. No significant differences in TRM, PFS and OS were observed between patients treated with melphalan 200mg/sqm, and patients treated with lower melphalan doses. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Scoring System for Predicting Risk of Relapse in Patients with Multiple Myeloma within Two Years after Stem Cell Transplantation

Novel drugs induction therapy followed with autologous stem cell transplantation (ASCT) is the first-line treatment for patients with multiple myeloma who suitable for ASCT, prolonging overall survival (OS) to approximately 7 years. However, some patients relapse within two years after transplantation and their prognosis is extremely poor. Identifying patients at high risk of early relapse might help clinicians propose alternative therapeutic strategies that improve outcomes. We retrospectively analyzed 641 multiple myeloma patients from 6 centers in China who received Bortezomib induction therapy followed by ASCT between June 1, 2006 and June 30, 2014. 181 patients (28.2%) progressed within two years after ASCT. Comparison of patients who progressed early [time to progression (TTP) < 2 year] and patients who did not (TTP ≥ 2 year) showed that those TTP < 2 yr had higher corrected calcium and lactate dehydrogenase (LDH) and more be in stage III of the International Staging System (ISS). 17p- was present in a significantly higher proportion of patients with TTP < 2 yr (P < 0.0001). Binary logistic regression identified the following four independent risk factors for TTP < 2 yr: ISS Ⅱ/Ⅲ, LDH > 240 U/L, presence of 17p- and HBsAg positivity. And these four independent risk factors were assigned scores using the regression coefficient β to predict relapse or progression within two years after ASCT, where LDH > 240 U/L was given a score of 2.0; 17p-, a score of 3.9; ISS II/III, a score of 3.8; and HBsAg positive, a score of 1.9. Based on total scores, patients were classified into three risk groups: the low-risk group (score < 4): 6.9% relapsed within two years of ASCT; the medium-risk group (score 4-8): 45.8% relapsed within two years; and the high-risk group (score > 8): 89.3% relapsed within two years. Based on this scoring system, TTP was analyzed for the 641 patients. TTP was not achieved in the low-risk group, while 25.6 months in the medium-risk group and 16.5 months in the high-risk group (Figure 1). The differences among the groups were significant. It is a useful scoring system for predicting risk of relapse within two years after ASCT in patients with multiple myeloma. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Phase II Trial of Bortezomib Plus Rituximab As Maintenance Therapy Post ASCT for Patients with Mantle Cell Lymphoma

Background:The standard of care for younger patients with mantle cell lymphoma is induction chemotherapy followed by autologous stem cell transplantation (ASCT). Rituximab (R) maintenance therapy post induction has been shown to improve overall survival (OS) (Kluin-Nelemans et al. NEJM 2012), and R maintenance post ASCT has been shown to improve progression free survival (PFS) (Graf SA et al. Ann Oncol 2015) and OS (Le Gouill S et al. ASH 2016). Bortezomib as consolidation has been shown to be feasible and tolerable in patients with MCL post ASCT (Kaplan L et al, ASH 2015). We hypothesize that the combination of bortezomib plus R as maintenance therapy post ASCT in patients with MCL may increase the disease free survival (DFS). We report our final results including quantitative CCND1 mRNA monitoring for minimal residual disease.Methods:This is a multicenter phase II maintenance study in patients with MCL post ASCT. Bortezomib was given at 1.3 mg/m2SQ once a week for 4 weeks every 3 month for 2 years. Rwas given at 375 mg/m2 IV once a week for 4 weeks every 6 months for 2 years. CT and/or FDG-PETwere performed at every 6 months. The primary endpoint was to reach a 2 year DFS of > 80%. Secondary endpoints included toxicity, relapse rate, OS, and CCND1 mRNA as MRD monitoring. Peripheral Blood was collected at baselineand on day 1 of each cycle (3 month interval), and CCND1 mRNA was assessed using droplet digital PCR technology (ddPCR) on RNA extracted from peripheral blood mononuclear cells. JVM2 (MCL cell line), normal healthy patient, and an untreated patient with MCL involvement served as controls. Absolute transcript concentrations were normalized to HPRT1 (housekeeping gene) followed by a normalization to the positive control, JVM2 (100%).Results:Twenty three patients were accrued, with 23 eligible for analysis. Majority of the patients were male (96%), received ASCT and maintenance therapy in CR1/PR1 (91%), had advanced stage at diagnosis (70% stage IV), and considered young with a median age of 59 (45-66). About half had low risk disease by MIPI and half with intermediate to high risk disease. The median follow- up was 29.8 months. The 2 year DFS is 89.7% (95% CI: 64.8-97.3) and 2 year OS is 94.7% (95% CI: 68.1-99.2) for the whole cohort (Figure 1). The 2 year DFS is 94.4% (95% CI: 66.6-99.2) and 2 year OS is 100% (95% CI: NA) for the 21 patients who received induction therapy followed by ASCT and R maintenance in CR1/PR1. Two patients who entered trial had relapsed/refractory MCL.Treatment was well tolerated. The median number of completed cycle was 8/8 (1-8) with a median duration of therapy of 19.9 month. Grade 3/4 toxicities possiblyattributable to study drug included neutropenia (n=17), lymphopenia (8), pneumonia (2), anemia (2), skin infection (1), hyperglycemia (1), and thrombocytopenia (1). Grade 2 possibly related toxicities that occurred in > 10% included upper respiratory tract infection (5), hypertension (5), diarrhea (3), fatigue (3), neutropenia (1), and thrombocytopenia (3). With regard to the specific adverse event of peripheral sensory neuropathy, Grade 1 event occurred in 10 patients and Grade 2 in 2 patients. There were no treatment discontinuations due to neutropenia or neuropathy. There were 2 death on study, 1 from relapsed MCL and 1 from alloHCT for MDS.MRD monitoring was performed on 18 patients seen at COH. Twelve out of 18 patients had at least 36 months analysis while 6/18 had less than 12 months for analysis. High CCND1 mRNA was detected in an untreated patient (control) with MCL involvement and JVM2 cell line. Low CCND1 mRNA was detected in normal healthy control, all samples while on maintenance R, and all patients without radiographic progression of disease (Figure 1). . Unfortunately, no samples were obtained on the two patients who developed progressive disease (1 due to withdraw of consent prior to relapse, the other due to urgency of treatment).Conclusions: The combination of bortezomib with R as maintenance therapy for MCL is well tolerated post ASCT and has met the primary endpoint of prolonging 2 year DFS. Quantitative CCND1 mRNA monitoring by ddPCR is feasible and appears to correlate with clinical remission status. The combination therapy of bortezoimb and R maintenance therapy post ASCT and CCND1 mRNA MRD monitoring method warrants further investigations. [Display omitted] DisclosuresChen:Pfizer: Consultancy; Seattle Genetics: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Genentech: Speakers Bureau; Affimed: Research Funding. Nademanee:seattle Genetics: Speakers Bureau. Siddiqi:Juno: Other: Steering committee for JCAR017; Seattle Genetics: Speakers Bureau; Pharmacyclics, an AbbVie Company: Other: Steering committee for ibrutinib, Speakers Bureau. Kwak:Pepromene Bio: Consultancy, Equity Ownership; Celltrion, Inc: Consultancy; InnoLifes: Consultancy, Equity Ownership. Holmberg:Seattle Genetics: Research Funding; Sanofi: Research Funding; Merck: Research Funding; Millennium: Research Funding; JAZZ: Consultancy; Up To Date: Patents & Royalties.

Chidamide, a HDAC Inhibitor, Combined with Cladribine, High Dose Gemcitabine and Busulfan with Autologous Stem Cell Transplantation in Patients with Relapsed/Refractory and Poor-Risk Lymphoma

IntroductionHigh dose chemotherapy (HDC), such as carmustine/etoposide/cytarabine/melphalan (BEAM), followed by autologous stem cell transplantation (ASCT) was a standard of care for patients with relapsed/refractory and poor-risk lymphomas for over decades. However, with the introduction of new drugs, such as rituximab, patients relapsed from or refractory to first line therapy benefit less from HDC with ASCT. To improve the survival of these patients with ASCT, better HDC combination is urgently needed. Our previous research indicated the combination of cladribine/gemcitabine/busulfan (CGB) had strong synergistic effect against lymphoma cell lines. Adding Histone deacetylases inhibitor (HDACi), vorinostat or chidamide (chi), to CGB further enhanced cytotoxicity, which warrant the clinical use of ChiCGB combination as conditioning chemotherapy. We started a phase II clinical trial to evaluate the efficacy and safety of ChiCGB followed by ASCT in patients with relapsed/refractory and poor-risk lymphomasPatients and methodsEligibility included ages 18 to 65 and one of the following lymphomas: High-risk and relapsed/refractory (R/R) diffuse large B cell lymphomas (DLBCL), T and natural killer/T (NK/T) cell lymphoma, and hodgkin lymphoma (HL). Additional eligibility criteria included adequate renal, hepatic, pulmonary, cardiac function, performance status 0 to 1, no active hepatitis B or C.Patients received oral chidamide 30mg on days -7, -4, 0, +3. Cladribine was administered intravenously at the dose of 10 mg from days -6 to -2. Gemcitabine was administered intravenously 4 hours after the finish of cladribine at the dose of 2500 mg/m2 on days -6 and -2. Busulfan was administered intravenously at dose of 3.2 mg/kg on days -6 to -2. Dexamethasone 10 mg i.v. was given from day -6 to -2. Infusion of peripheral blood stem cells was on day 0.CR, OS and progression free survival(PFS) were calculated using standard methods. Statistical analysis was done using Fishers exact test or Chi-square test / Kruskal-Wallis test. Kaplan-Meier method was used for time-to-event analysis including overall survival and progression free survival. The Wilcoxon test was used to evaluate the difference in time-to-event endpoints between patient groups.ResultsForty-three patients were enrolled between Apr. 2015 and Apr. 2017. Median age was 34 years (range, 22-62). The diagnoses were DLBCL (N=19), T&NK-NHL (N=20), HL (N=4). Eight patients had double/triple protein expression of C-myc, Bcl-2 or Bcl-6 protein identified by immunohistochemistry; 2 had IVLBCL; 1 had transformed DLBCL; 13 had stage IV extranodal natural killer/T cell lymphoma (ENKTCL); and 2 had lymphoblastic T cell lymphoma. Twenty-tow patients were in first CR, 21 had R/R disease, and 5 had PET positive tumor before HDC.Stem cells source was peripheral blood. Median infused CD34+cells count was 2.1×106/Kg (range, 1.0 to 11.6×106/Kg). Neutrophils and platelets were engrafted on a median day +11 (range, days +8 to +14) and day +12 (range, days +9 to +22), respectively.The median follow-up is 10.3 months (range, 3-26.5 months). The progression free survival (PFS) and overall survival (OS) of the whole cohort are 78.2% and 89.5%, respectively (Figure-1A). The PFS and OS in DLBCL group are 81.7% and 100% respectively (Figure-1B). Of 19 patients with DLBCL, only 2 with IVLBCL relapsed at 5.7 and 11.1 months post transplantation respectively. The EFS and OS in T&NK/T group are 73.7% and 78.8%, respectively (Figure-1C). Twelve of 16 patients with ENKTCL, 1 of 2 patients with lymphoblastic T cell lymphoma and 1 of 2 patients with T-NHL remain alive in CR at last follow-up. The EFS and OS in HL group are 75% and 100%, respectively. For the whole cohort, patients who had active disease before HDC demonstrated poorer EFS (80.9% vs. 53.3%; P=0.039) (Figure-1D).The most common adverse event was infection. Thirty-nine (90.7%) patients developed grade 3 neutropenic fever. Other notable toxicities included grade 2 (55.8%) and 3 (9.3%) mucositis, grade 2 (13.9%) and 3 (4.7%) dermatitis, grade 2 (9.3%) diarrhea and self-limited transaminase elevation. All these toxicities were manageable and there was no therapy-related mortality.ConclusionOur study showed ChiCGB combination can be safely administered as HDC before ASCT for patients with R/R or high-risk lymphomas. This combination showed promising early outcomes and warrant further clinical investigations. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Consolidation with Bortezomib, Lenalidomide and Dexamethasone Upgrades the Complete Remission Rate after Autologous Hematopoietic Cell Transplantation in Patients with Multiple Myeloma

Introduction : High-dose therapy (HDT) combined with autologous stem cell transplantation (ASCT) is a standard front-line treatment strategy for patients with newly diagnosed multiple myeloma (MM). Unfortunately, almost all the patients will eventually relapse, emphasizing the need for new treatment options or strategies to improve outcomes in these patients. A recent meta-analysis clearly demonstrated that post-transplant lenalidomide maintenance improves overall survival (OS), conflicting results were reported on the benefit of early post-transplant consolidation with bortezomib, lenalidomide, and dexamethasone (VRD). The aim of this study was to assess the effect of VRD consolidation on complete remission (CR) rate at Day100 post ASCT, a surrogate marker for progression free survival (PFS) and OS.Methods: This study was conducted at the American university of Beirut Medical Center, Lebanon. A total of 42 patients newly diagnosed with MM had received ASCT, followed by a total post-transplant treatment consisted of 2 cycles of VRD consolidation and maintenance lenalidomide. These patients were treated and followed between 2011 and 2016. All patients received pre-transplant bortezomib based induction. Of them, 17 (41%) patients had VRD triplet combination. The conditioning regimen consisted of high dose melphalan. The consolidation regimen consisted of bortezomib 1.3 mg/m2 I.V. (days 1, 8, 15 and 22 of each 28-day cycle), lenalidomide 25 mg orally daily for 21 days every 28 days, dexamethasone 20 mg total orally (days 1, 8, 15 and 22 of each 28-day cycle) for a total of 2 cycles. Patients and disease characteristics are summarized in table 1.Results: Median age at transplantation was 55 (41-75) years. Median time from diagnosis to transplant was 5 (3-49) months. The median number of days to reach an absolute neutrophil count more than 500/mm3 post-ASCT was 11 days. VRD consolidation therapy was initiated at a median of 59 (34-201) days from transplantation. In total, 40 (95%) patients completed 2 cycles of VRD without grade 3/4 adverse events. One patient could not receive bortezomib during cycle 2 because of severe peripheral neuropathy. All patients received maintenance with lenalidomide. At time of transplant, only 4 (10%) patients were in complete remission (CR), 25 (59%) patients in very good partial remission (VGPR), and 11 (26%) patients in partial remission. Day 30 evaluation post-transplant, 11 (26%) patients were in CR, 6 (14%) patients in VGPR. Importantly, assessment of disease status at day 100 post-transplant identified 17 (40%) patients in CR. After a median follow up of 26 months, the 2 years PFS was 81% and OS was 92.9%.Conclusion: VRD consolidation significantly upgrades the CR rate after ASCT in patients with MM. These encouraging findings need to be verified and confirmed in prospective randomized trials, establishing a new standard of post-transplant treatment in MM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

CD34+ Cell Count and Disease Free Survival in Patients with Diffuse Large B Cell Lymphoma Who Have Received Autologous Stem Cell Transplantaion

BackgroundThere are still varied opinions on the course of disease for patients who have received autologous stem cell transplantation (ASCT) depending on the dose amount of infused CD34+. Some studies report that higher amount of infused CD34+ cell dose would increase recurrence rates. On the other hand, some other studies suggest higher infused CD34+ cell leads to less recurrence and increase in DFS. We tried to identify the difference in recurrence with ASCT patients depending on the dose amount of infused CD34+ cell.MethodsWe conducted a retrospective analysis of 158 diffuse large B cell lymphoma (DLBCL) patients who underwent ASCT in a single center from March 1996 to May 2017. We excluded Primary CNS lymphoma patients who received upfront ASCT. We compared the disease free survival (DFS) by dividing patients into five groups: less than 3x108/kg (group1), between 3x108/kg and 5x108/kg (group2), between 5x108/kg and 6x108/kg (group3), between 6x108/kg and 10x108/kg (group4) and more than 10x108/kg (group5) depending on the amount of infused CD34+dose.ResultsThe number of patients in each group was 5(group1), 13(group2), 47(group3), 57(group4) and 36(group5). Baseline sex, age, stage at diagnosis, number of extranodal involvement, IPI score, whether Germinal center B-cell like diffuse large B-cell lymphoma or not, treatment type did not differ in each group. There was no statistical difference in the number of induction chemotherapy line before ASCT between group1 and group5 (p -value=0.196) as well as between each other groups.Mean DFS was 2.36, 18.0, 19.33, 27.16 and 56.21 months in group1, 2, 3, 4, 5, respectively. There were statistically significance in the difference of DFS between group1 and group3 (p -value=0.029), between group1 and group4 (p -value=0.033), between group1 and group5 (p -value=0.008) and between group3 and group5 (p -value=0.044). DFS value seemed to increase with the increasing amount of infused CD34+ cell dose.ConclusionsIn our study, DFS had an increasing tendency with increasing amounts of infused CD34+ cells. The recurrence rate decreased as the infused CD34+ cell dose was higher. These data suggest that higher amount of infused CD34+ cells may increase DFS in patients with DLBCL who undergo ASCT. DisclosuresNo relevant conflicts of interest to declare.

High-dose lenalidomide and melphalan as conditioning for autologous stem cell transplantation in relapsed or refractory multiple myeloma.

8021 Background: Autologous stem cell transplantation (ASCT) remains a standard of care of eligible patients with multiple myeloma, despite the many novel therapies introduced over the past decade. High dose melphalan (HDM) is the only approved regimen to date. Lenalidomide (LEN) is an oral immunomodulatory drug which has become the backbone of myeloma therapy from induction through salvage and maintenance. Early studies noted a dose response relationship, and found myelosuppression to be the dose limiting toxicity. We previously reported on our phase 1 study of high dose lenalidomide (HDLEN) with HDM in conditioning for ASCT, where no DLT was noted up to 350mg PO daily of LEN. Here we report the phase 2 data of patients undergoing ASCT with combination conditioning regimen. Methods: 50 patients with relapsed/refractory multiple myeloma (RRMM) underwent ASCT using HDLEN+HDM conditioning. HDLEN was dosed at 350mg PO daily from day -5 to day -1 and HDM was dosed 100mg/m2 on days -2 and -1. TPatients were heavily pre-treated: 32% had prior HDM-ASCT, 96% had received prior lenalidomide, and 42% prior pomalidomide; 40% prior anti-CD38 mAB. Of note, 68% entered the study with progressive disease at time of enrollment. Results: Overall response rate was 96%, with 80% being ≥VGPR. Median progression free survival (PFS) was noted at 14.3 months, while overall survival (OS) was 68.2 months. PFS was similar when patients were stratified by prior ASCT, depth of response at enrollment, or presence of high risk FISH. Toxicities were mostly hematologic (100% neutropenia and thrombocytopenia, 90% anemia), GI (88% diarrhea, 72% nausea, 42% vomiting) and metabolic (30-96% derangement in electrolytes), and similar to historical controls receiving HDM alone. Second malignancies were noted in 2 patients. Conclusions: HDLEN/HDM is a well tolerated and effective conditioning regimen for ASCT in patients with RRMM. This regimen merits further investigation as ASCT is likely to remain an integral part of the treatment of RRMM patients, yet few advancements have been made to this modality. HDLEN may be particularly useful in patients with high risk disease and those progressing after multiple lines of therapy. HDLEN added little toxicity to HDM and SPMs were not more frequent than expected per SEER database for patients in this age range. Clinical trial information: NCT01054196. [Table: see text]

Progression-free survival at 24 months as a landmark after autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma.

7522 Background: Patients with newly diagnoseddiffuse large B-cell lymphoma (DLBCL) who achieve event-free survival at 24 months (EFS24) following immunochemotherapy (IC) have excellent overall survival (OS) similar to that of age- and sex-matched general population. The standard of care for patients with relapsed or refractory (RR) DLBCL following frontline IC is salvage therapy followed by autologous stem cell transplant (ASCT). The goal of this study is to evaluate the role of progression-free survival (PFS) at 24 months (PFS24) as a landmark after ASCT in patients with RR DLBCL. Methods: Patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Post-ASCT PFS, OS, and post-relapse survival (PRS) were plotted by Kaplan-Meier method, and cumulative incidences of relapse vs non-relapse mortality (NRM) and different causes of death were compared accounting for competing events. Statistical analyses were performed in EZR v1.54. Results: A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow up of 8.0 years (95% CI 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, post-ASCT relapse rate was much higher than NRM rate (48.1 vs 9.1% at 5-year). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and NRM were similar (14.8% and 12.3% at 5-year). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma related and unrelated death rates were similar after achieving PFS24 (Table). For all patients who had a post-ASCT relapse, median PRS was 0.7 years (95% CI 0.5-0.9), and late relapse ( &gt; 2 vs ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] vs 0.5 [0.3-0.7] years, p &lt; 0.001). Conclusions: Post-ASCT PFS24 is an important prognostic predictor of post-ASCT outcomes in patients with RR DLBCL following frontline IC.[Table: see text]

Clinical value of minimal residual disease assessed by multiparameter flow cytometry in amyloid light chain amyloidosis.

To assess the feasibility and prognostic value of minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in newly diagnosed amyloid light chain (AL) amyloidosis. Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested at 3 months after first-line therapy completion were retrospectively analysed in a single centre from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD plus sequential autologous stem cell transplantation (ASCT), both without maintenance therapy. Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. Baseline characteristics were not different between MRD-negative and MRD-positive patients. More ASCT patients than non-ASCT patients (90.0% vs 53.3%, p = 0.043) achieved MRD negativity. In the MRD-negative and MRD-positive groups, cardiac response was observed in 93% and 25% (p = 0.019) and any organ response in 94% and 50%, respectively (p = 0.023). At a median follow-up of 25.1 months, MRD-negative patients showed significantly longer progression-free survival (PFS) from diagnosis than MRD-positive patients (24.52 vs 76.39 months, p = 0.004). MRD negativity measured by MFC at 3 months after first-line therapy completion in patients with AL amyloidosis is measurable and associated with improved organ response rates and PFS over a long follow-up.

Association of CD 34 positive cell dose with engraftment kinetics in autologous peripheral blood stem cell transplant patients of multiple myeloma

BackgroundTreatment with high-dose chemotherapy and stem cell transplantation has prolonged survival in patients of multiple myeloma (MM). A dose-response relationship between number of CD34+ cells infused and leukocyte and platelet recovery, exists. Patients receiving dose of <2.0 × 106 CD34+ cells/kg have delayed engraftment. The level of optimal cutoff for accelerated engraftment is yet to be validated. Hence, this study was undertaken to study the association of CD 34+ cell dose with engraftment kinetics in patients of MM who underwent autolgous peripheral blood stem cell transplant (PBSCT). MethodsWe retrospectively analyzed 19 patients of MM who underwent PBSCT at our center between December 2016 to December 2018. Complete blood counts were carried out daily after transplantation to record neutrophil and platelet engraftment. ResultsBased on the CD34+ cell dose given : <5 × 106/kg (category 1), 5−10 × 106/kg (category 2), >5 × 106/kg (category 3), the mean (SD) neutrophil engraftment time was 11.3 (0.5) days, 10.6 (0.9) days, and 10.2 (1.3) days respectively. Platelet engraftment time was 12.4 (2.60) days, 10.6 (1.14) days, and 11.2 (1.64) days for category 1, 2, and 3 patients, respectively. Correlation co-efficient between CD 34+cell dose and days for neutrophil and platelet engraftment was found to be −0.24 and −0.20, respectively. Time for neutrophil engraftment was found to be significantly associated with CD34+ cell dose category. ConclusionCD 34+ cell dose appears as the strongest predictor of leukocyte and platelet engraftment. CD 34+ cell dose of >5.0 × 106 cells/kg leads to an accelerated neutrophil and platelet engraftment in patients of MM.

Prognostic impact of early-versus-late responses to different induction regimens in patients with myeloma undergoing autologous hematopoietic cell transplantation: Results from the CALM study by the CMWP of the EBMT.

In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor). The length of induction treatment required to achieve a Good response did not affect PFS (P=.65) or OS (P=.61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8months (P=.31), and median OS 81.7, 92.7, and 77.4months, respectively (P=.83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR=1.21, P-value=.02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post-transplant. The kinetics of response did not affect outcomes.

Survival in patients with high-risk neuroblastoma treated without autologous stem cell transplant or dinutuximab beta

The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with nonmyeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with nonmyeloablative consolidation. A tabulated compilation of similar reports is included. A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, followed by consolidation. Consolidation involved 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in the clinic. Subsequent treatment included radiotherapy to the primary tumor and differentiation therapy with isotretinoin. Over 7½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The median follow-up of disease-free patients was 49 months (IQR: 45, 79). Patients with relapse were not treated further. A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid decision-making for care of patients in LMIC while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.

133 - Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Adult Autologous Hematopoietic Stem Cell Transplant Patients

133 - Olanzapine for the Prevention of Chemotherapy Induced Nausea and Vomiting in Adult Autologous Hematopoietic Stem Cell Transplant Patients

Characteristics of respiratory virus infections in autologous hematopoietic stem cell transplantation patients, a prospective study, Bern, Switzerland, 2015–2017

Background The epidemiology of respiratory virus infections (RVI) in patients undergoing autologous haematopoietic stem cell transplantation (auto-SCT) is not well described. Methods Our goal was to describe the epidemiology of respiratory virus infections (RVI) in patients undergoing autologous haematopoietic stem cell transplantation (auto-SCT) in a single tertiary centre observation study during two respiratory virus seasons (2015–2017). All symptomatic auto-SCT patients were tested for RVI by nasopharyngeal swab. Results 156 transplantation episodes were included, 69% were male and, the median age was 57 years. We detected 19 RVIs in 156 transplantation episodes (12%). The median time to RVI after hospitalization was 13 days [IQR 7–13] and 15/19 (79%) had a possible nosocomial origin (occurrence ≥ 5 days after admission). The nosocomial infections included 5/15 (33%) ‘severe’ RVIs (3 influenza viruses, 1 parainfluenza virus, and 1 adenovirus) as well as 10/15 (66%) non-severe virus infections (including human rhinovirus and human coronavirus). Conclusion In approximately 10% of auto-SCT transplantation episodes, an RVI with likely nosocomial origin was detected and included ‘severe viruses’ such as influenza. Our study suggests that infection prevention measures in auto-SCT patients can be improved. Abbreviations AdV: adenovirus; ALL: acute lymphatic leukaemia; AML: acute myeloid leukaemia; auto-SCT: autologous haematopoietic stem cell transplantation; hCoV: human coronavirus; HD: Hodgkin’s disease; hMPV: human metapneumovirus; HRV: human rhinovirus; HSCT: allogeneic haematopoietic stem cell transplantation; IQR: interquartile range; GCT: germ cell tumour; MM: multiple myeloma; NHL: non-Hodgkin lymphoma; PIV: parainfluenza virus; RSV: respiratory syncytial virus

HEMATOPOIETIC STEM CELL TRANSPLANT IN AGGRESSIVE T AND NK/T CELL LYMPHOMA - ROLE OF UPFRONT AUTOLOGOUS TRANSPLANT IN NODAL PERIPHERAL T-CELL LYMPHOMA.

Aggressive T and NK/T-cell lymphoma are known to have a high risk of relapse and poor long-term prognosis. Hematopoietic stem cell transplantation has been performed as part of consolidation or salvage treatment. We retrospectively studied the outcomes of autologous (A) and allogeneic (allo) hematopoietic stem cell transplantation (SCT) in aggressive T and NK/T-cell lymphoma at our center between 2010 to 2020. Patients with nodal peripheral T-cell lymphoma (PTCL) that were younger than 65 years old who did not receive upfront autologous SCT (ASCT) at first complete remission were selected from our registry data for further comparison. Thirty-six patients underwent ASCT, and 16 patients underwent alloSCT. In the ASCT cohort, 18 patients with nodal PTCL who underwent upfront ASCT at first complete remission (upfront ASCT) were compared with 15 patients with nodal PTCL who were in first complete remission after single-line induction but did not receive ASCT. The two-year progression-free survival (PFS) and overall survival (OS) rates for the ASCT cohort were 58% and 73%, respectively. The two-year PFS and OS for the alloSCT cohort were 47% (P=0.35, P=0.02, respectively). Twenty-four patients who received SCT at first remission (21 ASCT and three alloSCT) had a two-year PFS and OS of 75% and 89%, respectively. In comparison, 28 patients who received SCT at relapse/refractory (15 ASCT and 13 alloSCT) had a two-year PFS and OS of 40% and 50%, respectively (P=0.047, P=0.024, respectively). Patients in complete remission prior to transplantation (n=42) had a two-year PFS and OS of 59% and 73%, respectively. In contrast, patients in partial remission prior to transplantation (n=10) had a two-year PFS and OS of 40% and 48%, respectively (p>0.05). Non-relapse mortality occurred in 6% and 43% of ASCT and AlloSCT, respectively. Multivariate analysis revealed that EBV-positivity at diagnosis indicated poorer PFS. EBV-positivity at diagnosis and more than two prior lines of treatment at transplant were associated with poorer OS. For nodal PTCL, the two-year PFS and OS were 79% and 100% for the upfront ASCT cohort and 78% and 92% for the non-upfront ASCT cohort, respectively (p>0.05). Hematopoietic SCT is a feasible treatment option for aggressive T and NK/T-cell lymphoma. Patients who underwent SCT at first remission had better survival rates than those who underwent SCT at relapse/refractory. Nevertheless, due to the limited sample size of the current study, the role of upfront ASCT in patients with nodal PTCL who achieved first complete remission remains unclear.

Quality of life and changes in the social dimension of hematopoietic stem cell transplants recipients.

to assess/correlate health-related quality of life with the social dimension of hematopoietic, autologous and allogeneic stem cell transplant patients in the three years post-transplant. longitudinal, observational study with 55 patients, in a reference hospital in Latin America, from September 2013 to February 2019, using the Quality of Life Questionnaire-Core and Functional Assessment Cancer Therapy Bone Marrow Transplantation. A total of 71% underwent allogeneic transplantation. The social dimension had low averages since the baseline stage (55, 21) and low scores (56) for quality of life in pancytopenia. There was a significant positive correlation between social dimension, quality of life in pancytopenia (p<0.01) and follow-up after hospital discharge (p<0.00). There is a significant difference (p<0.00) throughout the stages, however, not in terms of the type of transplant (p>0.36/0.86). patients with better assessments in the social dimension have a better quality of life. Interventions focusing on the multidimensionality of the quality of life construct are necessary.

Infections in hematopoietic stem cell transplant patients admitted to Hematology intensive care unit: a single-center study

ABSTRACT Objective The aim of this study was to investigate the data of HSCT patients who were admitted to our Hematology ICU due to infections or infectious complications. Materials and Methods HSCT patients who were admitted to our Hematology ICU between 01 January 2014 and 01 September 2017 were analyzed retrospectively. Results 62 HSCT patients were included in this study. The median age was 55.5 years and 58% of the patients were allogeneic HSCT patients. Major underlying hematologic disorders were multiple myeloma (29%) and lymphoma (27.4%). The most common reasons for ICU admission were sepsis/septic shock (61.3%) and acute respiratory failure (54.8%). Overall ICU mortality rate was 45.2%. However, a lot of factors were related with ICU mortality of HSCT patients in univariate analysis, only APACHE II score was found to be an independent risk factor for ICU mortality. While there was infection in 58 patients at ICU admission, new infections developed in 38 patients during ICU stay. The most common new infection was pneumonia/VAP, while the most frequently isolated bacteria were Acinetobacter baumannii. Length of ICU stay, sepsis/septic shock as a reason for ICU admission and the presence of urinary catheter at ICU admission were determined factors for ICU-acquired infections. There was no difference between autologous and allogeneic stem cell transplant patients in terms of ICU morbidities and mortality. However, pneumonia/VAP developed in the ICU was higher in autologous HSCT patients, while bloodstream/catheter-related bloodstream infection was higher in allogeneic HSCT patients. Conclusion It was concluded that early or late post-HSCT infections and related complications (sepsis, organ failure, etc.) constituted a major part of the reasons for ICU admission, ICU mortality and ICU morbidities.