Time Of Autologous Stem Cell Transplantation Research Articles

PS1534 EFFICACY AND SAFETY OF STEM CELL MOBILISATION FOLLOWING GDP SALVAGE IN PATIENTS WITH RELAPSED OR REFRACTORY LYMPHOMA

Background:High‐dose chemotherapy and autologous stem cell transplant (ASCT) remains a key treatment strategy in patients with relapsed/refractory (R/R) aggressive lymphoma. CCTG study LY.12 established gemcitabine, dexamethasone and cisplatin (GDP) as a standard salvage chemotherapy regimen for R/R lymphoma across Canada. Peripheral blood stem cell (PBSC) mobilisation on this salvage regimen can be achieved using granulocyte colony‐stimulating factor (GCSF) during salvage (GDP) or following an additional course of cyclophosphamide and etoposide (CE) at completion of salvage GDP; however these strategies have yet to be compared.Aims:To compare the efficacy and safety of PBSC mobilisation with GDP to our previous standard of CE since GDP was adopted as standard salvage therapy for R/R lymphoma.Methods:All patients undergoing PBSC mobilisation following salvage GDP for R/R lymphoma from January 2012 to August 2018 were included in this analysis. CE comprised C 2 g/m2 d1, E 200 mg/m2 d 1–3, and GCSF 10 μg/kg d4–12, with apheresis planned d13. For collection following GDP, GCSF was added 10 μg/kg d9–14, apheresis starting d15. Apheresis started when the blood CD34 count was ≥10 cells/μl, with target collection of ≥5 x 106 CD34+ cells/kg. From May 2014 plerixafor 24 μg/kg was added to GCSF in the event of slow or inadequate mobilisation. Primary outcomes were PB CD34+ count on planned day of apheresis and total CD34+ yield. Secondary outcomes included number of apheresis days, febrile neutropenia after mobilisation, time to engraftment, days admitted for transplant, blood product usage, PFS and OS.Results:A total of 339 patients underwent PBSC mobilisation, 210 following GDP and 129 after CE. Patients in the GDP group had more delays from planned to actual day of collection (mean 0.7 vs 0.4 days, p = 0.006) and required more total days of apheresis (median 2 vs 1 day; p = 0.001). The percentage of GDP patients collected on planned day of harvest and who required only one day of apheresis were 71% and 50% respectively, versus 84% and 69% respectively after CE. ROC curves (Figure 1) for platelets, neutrophils and PB CD34+ measured on planned day of collection confirm PB CD34+ as the best predictor for successful attainment of target CD34+ yield. In multivariable analysis, CE led to both higher PB CD34+ count on planned day of harvest and higher total CD34+ yield (both p < 0.001), despite a higher rate of plerixafor use in the GDP group (37/210 vs 6/129). However, when considering a target total CD34+ yield ≥5x106/kg there was no difference between mobilisation regimens (p = 0.66). Similarly, on multivariable analysis, days to engraftment, ASCT admission duration and platelet transfusions required showed no statistical difference between the two mobilisation strategies; patients mobilised with CE required more RBC transfusion during ASCT (p = 0.04). Of interest, prior bone marrow involvement and use of plerixafor were both predictors for longer engraftment time (p = 0.013 and p = 0.007 respectively), after adjustment for mobilisation and CD34+ yield. Although total CD34+ yield was not associated with days to engraftment on multivariable analysis, it was independently associated with blood product usage and day 100 blood count recovery. In multivariable Cox analyses, disease status at time of ASCT was the main predictor of PFS and OS.Summary/Conclusion:While CE/GCSF appears to be a more efficient method of mobilisation in patients undergoing GDP salvage for R/R lymphoma, this did not translate to significant differences in clinical outcomes such as engraftment or duration of hospital admission.image

PS1373 A TWENTY‐FOUR YEAR EXPERIENCE OF AUTOLOGOUS STEM CELL TRANSPLANTATION FOR LIGHT CHAIN AMYLOIDOSIS PATIENTS IN THE UNITED KINGDOM

Background:Autologous stem cell transplantation (ASCT) is considered to be the best method to improve long term survival outcomes in light chain amyloidosis (AL) patients, with a median survival of over 10 years. Crucially, the mortality has decreased over the decades mainly due to refinement of patient selection criteria.Aims:Our aim was to report the changing outcomes of a cohort of UK AL amyloidosis patients treated with ASCT.Methods:All patients with a proven histological diagnosis of amyloidosis and treated with an ASCT from 1994–2018 were identified from our database. Patient baseline characteristics were recorded including biomarker assessment and organ involvement, defined according to international criteria. Haematological response was assessed at six months and organ responses at 12 months, both calculated from the date of the ASCT and defined according to the international amyloidosis consensus criteria. The primary outcome was overall survival (OS), defined as time from ASCT to death. Secondary outcomes included: time to next treatment (TTNT), defined from date of ASCT to the start of next treatment, and transplant related mortality (all‐cause mortality before day +100 from return of stem cells). Survival outcomes were analysed using the Kaplan‐Meier method, with comparisons done using the log rank test. The Cox proportion hazards model was used to assess predictors of OS. All p‐values were two sided and any variable with a P value <0.10 on univariate analysis was included in the multivariate model.Results:Two hundred and sixty four patients were identified. The median age at time of ASCT was 57 years (30–70 years) and the median time from diagnosis to ASCT was 12 (0–263 months). The majority of patients were performance status 0 or 1 (84%). The median number of organs involved was two (range 1–4). The dominant organ involved was kidney (N = 180, 68.2%) with cardiac involvement in 32% (N = 85). The Mayo stage was 1: 44% (N = 63), 2: 39% (N = 56) and 3: 16% (N = 2). Eighty patients (30%) had an up‐front ASCT and 45% (N = 118) after first line treatment. Organ response was as follows: cardiac (N = 28, 60.9%), renal (N = 101, 76%) and liver (N = 7, 13.5%). The overall survival post ASCT (OS) was 87 months, (95% CI: 77–106 months) and overall treatment related mortality (TRM) was 8.7%, with a significant reduction over time: 1994–2000: 18.8%; 2001–2006: 13.6%; 2007–2012:6.2%; 2013–2018: 1.1%. A haematological response was achieved in 94.8% of patients and was a strong predictor of both survival (complete response (CR)/very good partial response (VGPR)‐139 (95% CI: 82–139 months) vs partial response (PR)/stable disease (SD)/progressive disease (PD)‐64 (95% CI: 50–92 months), P = 0.007), see figure, and TTNT (CR/ VGPR: 49 (95% CI: 24–48 months) vs. PR/SD/PD: 35 (95% CI: 9–20 months), P = <0.0001). Mayo stage (P = 0.037) and an abnormal ALP (P = <0.001) were independent predictors of OS on multivariate analysis.Summary/Conclusion:In conclusion this analysis of 264 patients with AL amyloidosis, treated with an ASCT over a 24 year period, confirms excellent long term outcomes and a marked improvement in TRM from 19% to 1% in the latest patient cohort. The median survival in patients achieving a CR response was 11.5 years. Outcomes are now comparable to large transplant centres in the United States. Given this improvement in TRM and long term survival, we confirm that ASCT still remains an important treatment modality for patients with systemic AL amyloidosis.image

Prognostic Significance of the Dynamic Change of Programmed Death-ligand 1 Expression in Patients with Multiple Myeloma.

BackgroundThe inhibition of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway has been shown to be an effective targeted therapy in fighting both solid organ cancers and hematological malignancies. PD-L1 expression also serves as a prognostic marker in various cancers. However, the expression of PD-L1 and its prognostic significance in multiple myeloma remains largely unknown.MethodsImmunohistochemistry staining of PD-L1 was performed in bone marrow biopsy samples (total of 85 samples) in 32 myeloma patients receiving autologous stem cell transplant (ASCT) at various time points: before ASCT, post-ASCT, and/or at relapse after ASCT. More than 1% of myeloma cells with PD-L1 staining was considered a positive expression of PD-L1. A correlation analysis was performed between post-ASCT overall survival (OS) and the status of PD-L1 expression.ResultsIn this pilot study, a total of 11 patients (34%) out of our cohort (32 patients) were positive for PD-L1 expression at least once during the course of the disease. A dynamic change of PD-L1 expression was noted in three patients converting from negative (before ASCT) to positive (post-ASCT) and two patients converting from positive (before ASCT) to negative (post-ASCT). Patients with positive PD-L1 expression persisting or occurring post-ASCT had shorter post-ASCT overall survival than those with negative PD-L1 expression post-ASCT (median survival: 13 vs 23 months, p<0.05). No significant differences were detected in the known prognostic factors between these two groups at the time of ASCT. Pre-transplant PD-L1 expression status, however, showed no significant impact on post-ASCT overall survival. Furthermore, a few patients switching from positive PD-L1 expression before ASCT to negative PD-L1 expression post-ASCT had a relatively good post-ASCT overall survival (n=2, overall survival of 29 and 56 months, respectively).ConclusionImmunohistochemistry can be reliably used for measuring PD-L1 expression in decalcified marrow core biopsy materials. Our results suggest that positive PD-L1 expression persisting/occurring post-ASCT could be an adverse prognostic marker for post-ASCT OS. Additionally, PD-L1 expression appears to be dynamic and is subjected to change after ASCT. Our findings suggest that periodically monitoring PD-L1 expression in patients with multiple myeloma post-ASCT is warranted. Further studies are needed to confirm our initial observation and to evaluate if timely intervention with PD-L1 blockade can improve post-ASCT outcomes in myeloma patients.

Autologous Stem Cell Transplantation in Central Nervous System Lymphoma: A Multicenter Retrospective Series and a Review of the Literature

BackgroundCentral nervous system (CNS) lymphoma is associated with poor outcomes. Autologous stem cell transplantation (ASCT) has been reported to improve outcomes when used as a consolidation strategy in primary CNS lymphoma (PCNSL) and as a salvage strategy in patients with disease relapse limited to the CNS. Herein, we describe our experience of using ASCT in PCNSL and secondary CNS lymphoma (SCNSL). Patients and MethodsWe evaluated clinical outcomes of 18 patients from 2 major academic centers with a median age of 55 (range, 46-72) years. Thirteen patients had PCNSL and 5 patients had SCNSL. Most of the cases were in the first (CR1) or second (CR2) complete remission (CR1 = 7, CR2 = 7) at the time of ASCT. Carmustine with thiotepa (n = 12, 67%) was the most commonly prescribed preparative regimen. ResultsThe median follow-up from ASCT for surviving patients was 12 (range, 0.9-115) months. The 2-year progression-free survival (PFS) and overall survival (OS) were 74% (95% confidence interval [CI], 48%-99%) and 80% (95% CI, 55%-100%), respectively. Two-year non-relapse mortality was 0%. The 2-year cumulative incidence of relapse/progression was 27% (95% CI, 10%-72%). In subgroup analysis of PCNSL patients, 2-year PFS, OS, and relapse were 71% (95% CI, 38%-100%), 71% (95% CI, 38%-100%), and 29% (95% CI, 9%-92%), respectively. ConclusionIn this retrospective study of patients with CNS lymphoma, consolidation with ASCT after high-dose methotrexate-based chemotherapy is safe and effective in reducing disease relapse.

Patterns of Relapse After Salvage Autologous Stem Cell Transplant for Hodgkin's Lymphoma: Should Sites of Relapse Relative to Initially Involved Sites Be Used to Guide Indications for Peri-Transplant Radiation Therapy

PurposeWe aimed to assess patterns of relapse in patients undergoing salvage autologous stem cell transplant (ASCT) for relapsed Hodgkin lymphoma in the modern era with the hypothesis that patients who suffer a relapse at initially involved sites are at increased risks of relapse post-ASCT that may help guide the application of peri-transplant radiation therapy. Methods and MaterialsA retrospective review was conducted of 38 patients undergoing ASCT between 2002 and 2017 for relapsed or refractory Hodgkin lymphoma. The site of relapse at the time of ASCT and subsequent relapses were compared with sites of the initial involvement at the time of diagnosis using follow-up imaging (most commonly positron emission computed tomography). Relapse and overall survival rates were calculated from the date of ASCT using the Kaplan-Meier method with a multivariate analysis, completed using a Cox multivariate analysis. ResultsThe median follow-up time was 38 months (interquartile range, 18-66 months). Twenty-two patients (58%) suffered a relapse after ASCT at a median time to relapse of 9.1 months (interquartile range, 2.9-12.3 months) with a 5-year risk of relapse of 58% (95% confidence interval [CI], 41%-75%). On univariate analysis, relapse at an initially involved site was significant for higher rates of relapse at 71% at 5-years (95% CI, 52%-90%) compared with relapse at initially uninvolved sites at 30% (95% CI, 2%-58%; P = .05). The relapse rate was also significantly higher in patients age <30 years at the time of diagnosis at 80% (95% CI, 59%-100%) compared with 40% (95% CI, 18%-62%) at 5 years in patients aged >30 years (P < .01). On multivariate analysis, relapse at initially involved sites was significant for higher rates of relapse (hazard ratio: 8.3; 95% CI, 1.2-57.4; P = .03). ConclusionsRelapses at initially involved sites may potentially increase the risk of relapse after ASCT. Additional studies are needed to clarify whether this should be used as an additional factor to guide recommendations for peri-transplant radiation therapy.

The Role of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in Multiple Myeloma: Immunomodulator Maintenance Post Autologous Stem Cell Transplant (ASCT) Predicts Better Outcome

▪Introduction: Multiple Myeloma (MM) is a clonal plasma cell malignancy, accounting for 10% of all hematological malignancies. Genetic analyses of large populations revealed that blood-specific somatic mutations in hematopoietic stem cells (HSCs) are commonly acquired during aging, a new entity labeled: clonal hematopoiesis of indeterminate potential (CHIP). We sought to determine the role of CHIP on survival of MM patients, specifically those receiving immunomodulator (IMiD) maintenance (Lenalidomide or Thalidomide) post autologous stem cell transplant (ASCT).Methods: We collected the cryopreserved, growth factor mobilized peripheral blood of 629 MM patients who underwent ASCT between 2003 and 2011 at the Dana-Farber Cancer Institute (DFCI). Then, we performed targeted next-generation sequencing using a 224-gene panel at a mean depth of coverage of 978X and ultra-low pass whole-genome sequencing at 0.1X to account for tumor contamination. We downloaded (dbGAP # phs000748.v6.p4) the whole-exome sequencing (WES) data of a cohort of 1144 newly diagnosed, untreated MM patients from the Multiple Myeloma Research Foundation (MMRF) Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass, NCT0145429) study (MMRC) and the WES data of a cohort of 205 newly diagnosed, untreated MM patients from the Broad Institute dataset. We analyzed their peripheral blood (average coverage of 108X) and tumor (average coverage of 107X) data separately, looking for the same CHIP genes included in our target bait panel.Results: The DFCI cohort had a median age of 58 years [range, 24-83] at time of ASCT and median follow up post ASCT of 8 years [range, 0.1-14.5]. 204 patients (32%) in the DFCI cohort had CHIP at time of ASCT. The most commonly detected mutated genes were DNMT3A, TET2, TP53, ASXL1 and PPM1D. 24 patients (3.8%) developed a second hematological malignancy at a median of 4 years [range, 1-10] post ASCT, half of whom had CHIP. Around 48% of the DFCI cohort received IMiDs as part of induction therapy. Different induction regimens had no effect on CHIP prevalence at time of ASCT. Around 56% of the DFCI cohort received IMiD maintenance, 22% of which received maintenance for at least 3 years [range, 0.06-12.8]. Among those who did not receive IMiD maintenance, patients with CHIP had worse progression free survival (PFS) (p-value < 0.001) and overall survival (OS) (p-value = 0.005). In patients receiving IMiD maintenance, having CHIP had no effect on PFS or OS. On the other hand, the MMRF cohort had a median age of 63 years [range, 27-93] and median follow up of 3.03 years [range, 0-5.9] from time of diagnosis. Around 52% of that cohort underwent ASCT and around 76% of those received IMiD maintenance with a median follow up of 2.7 years [range, 0-5.5] from time of ASCT. Furthermore, 200 patients of the MMRF cohort have follow-up samples of both tumor and peripheral blood that had targeted sequencing done by a 562-gene panel that included our genes of interest. Similarly, when studying the genomic results of 139 out of 1144 MMRF patients, as well as the 205 patients from the Broad Institute dataset, we detected CHIP in 25.6% of them and the top 5 most commonly mutated genes were similar to those of our cohort.Conclusion: CHIP is a common entity among MM patients, reaching a prevalence of up to 32%, that predicts a worse PFS and OS in those who do not receive IMiD maintenance therapy post ASCT. As expected, IMiD maintenance improves outcome in MM patients, with and without CHIP. In patients with CHIP, the use of IMiDs abrogated the deleterious effect imposed by CHIP to a point that outcome is identical to that of patients without CHIP. DisclosuresBustoros:Dava Oncology: Honoraria. Munshi:OncoPep: Other: Board of director. Anderson:Gilead: Membership on an entity's Board of Directors or advisory committees; OncoPep: Equity Ownership, Other: Scientific founder; Celgene: Consultancy; C4 Therapeutics: Equity Ownership, Other: Scientific founder; Bristol Myers Squibb: Consultancy; Millennium Takeda: Consultancy. Richardson:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Soiffer:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Ghobrial:Celgene: Consultancy; Janssen: Consultancy; BMS: Consultancy; Takeda: Consultancy.

Autologous Stem Cell Transplantation Is Effective in Chemosensitive HIV-Associated Lymphoma Irrespective of Previous Therapy and Histological Subtype

Introduction: Autologous stem cell transplantation (ASCT) is considered safe and effective in patients with HIV-associated lymphoma (HIV-Ly). The reported studies usually analyze togheter different histological subtypes, including classical Hodgkin lymphoma (HL) and a variety of aggressive non Hodgkin lymphoma (NHL), and different indications for ASCT, and report composite outcomes.Aim: We report our single center experience on a large single institution series of patients (pts) with HIV-Ly undergoing ASCT and analyse efficacy according to histology subtypes, indications for ASCT, previous therapy and lymphoma status at transplant, to understand the settings where this treatment approach is most effective and useful.Methods: Retrospective analysis of clinical characteristics and outcome of all consecutive pts with HIV-Ly transplanted at our Institution from March 2001 to February 2018.Results: 62 pts with HIV-Ly underwent ASCT during the study period. Ninety-four % were male; median age was 46 years (range, 29-62). Lymphoma histology was HL in 11 (18%), diffuse large B-cell lymphoma in 22 (35%), Burkitt or Burkitt-like in 13 (21%) , plasmablastic in 10 (16%), T-cell aggressive NHL (3 anaplastic large cell lymphoma, ALK negative, and 1 extranodal NK/T-cell lymphoma, nasal type) in 4 (6%), and indolent B-cell lymphoma (1 follicular lymphoma, and 1 extranodal marginal zone lymphoma) in 2 (3%) pts, respectively. Median CD4+ cells count at ASCT was 208/mL (range, 55-720); 8 pts (13%) had detectable HIV viral load. Eighteen pts (29%) had concomitant hepatitis C and 2 (3%) hepatitis B infection. Indications for ASCT were primary refractory disease (26%), first or subsequent relapse (37%), and consolidation after first line therapy for partial remission (PR) or high risk complete remission (CR) (37%). At the time of ASCT, 10 pts (16%) were in first CR, 45 (73%) had chemosensitive disease (i.e. first PR, chemosensitive relapse/refractory disease), and 7 (11%) had disease refractory to the last chemotherapy (CT) received. Twenty-three patients (37%) had received only 1 line of CT before ASCT, 29 (47%) 2 lines, and 10 (16%) 3 or more lines. Conditioning regimen was BEAM in 47 patients (76%), FEAM in 13 (21%), and 1 each Mitoxantrone-Melphalan and BiCNU-Thiotepa. All pts were receiving cART throughout ASCT except 3 who suspended cART for at least 1 week, due to toxicity and/or oral mucositis. Neutrophil engraftment (neutrophils > 500/mcl) occurred in all pts at a median of 10 days (range, 8-12), and platelet engraftment (platelet count > 20.000/mcl) occurred in all pts at a median of 13 days (range, 9-46), except in one with refractory disease who died of sepsis early after ASCT (treatment-related mortality 1.6%). Twenty-three pts (70%) experienced grade 3-4 toxicity, including oral mucositis (17 patients), gastrointestinal toxicity (8), hepatic toxicity (1), and seizures (1). Twenty-five pts (41%) had an episode of fever of unknown origin. Before engraftment, 22 documented bacterial infections, 1 fungal infection, 2 herpes zoster infections and 5 CMV reactivations were recorded. After a median follow-up of 59 months (range, 1-177) from ASCT, the 5 years-progression free survival (5y-PFS) and OS (5y-OS) were 66.6% and 69.7% respectively, with no significant differences according to different histologies (figure 1). The outcome was satisfactory regardless of the indication for transplant (primary refractory disease, 5y-PFS 50% and 5y-OS 49% , relapse, 5y-PFS 62.6% and 5y-OS 70.7%, and first line consolidation, 5y-PFS 80.3% and 5y-OS 80.1%, P=NS), and number of CT lines before ASCT (1 line, 5y-PFS 80.3% and 5y-OS 80.1%, 2 lines, 5y-PFS 61.3% and 5y- 63.4%, and 3 or more lines, 5y-PFS 53.3% and 5y-OS 66.7%, P=NS). According to the status of lymphoma at the time of ASCT, pts in first CR had a 5y-PFS of 77.8% and 5y-OS of 77.8% and pts with chemosensitive disease 73.7% and 80.3%, while all chemorefractory pts died within 5 months from ASCT, with median PFS and OS of 2 and 3 months respectively (P< 0.001) (figure 2).Conclusion: This is the largest single institution series of HIV-Ly receiving ASCT. We confirm the feasibility and long-term efficacy of this treatment approach in different histological subtypes. ASCT was beneficial also in primary refractory disease and heavily pre-treated pts, provided that lymphoma proved chemosensitive to the last CT received before ASCT. [Display omitted] DisclosuresRossi:ABBVIE: Other: ADVISORY BOARD; PFIZER: Other: ADVISORY BOARD; SANDOZ: Honoraria; GILEAD: Other: ADVISORY BOARD; AMGEN: Other: ADVISORY BOARD; SANOFI: Other: ADVISORY BOARD; JANNSEN: Other; JAZZ: Other: ADVISORY BOARD; TEVA: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD; ROCHE: Other: Advisory Board; NOVARTIS: Honoraria; MUNDIPHARMA: Honoraria; BMS: Honoraria.

Full Dose or Reduced Dose Melphalan (MEL) for Autologous Stem Cell Transplantation (ASCT) in Multiple Myeloma (MM): A Single Center Analysis on 187 Consecutive Patients

IntroductionMEL at the dose of 200 mg/m2 (MEL200) is considered the standard conditioning regimen before ASCT in MM patients (pts). Lower doses of 140 mg/m2 (MEL140) or 100 mg/m2 (MEL100) are used when toxicity is a concern. Whether these lower doses are equally effective is still a matter of debate and available data are conflicting.Aims and MethodsTo compare full dose with reduced dose MEL, we performed a retrospective analysis on MM pts in all disease stages treated at Jena University Hospital between 2003 and 2017. Statistical analysis included descriptive statistics and Cox regression. Progression free survival (PFS) and overall survival (OS) were calculated from the time of ASCT. Here, preliminary data on 187 pts are presented. For pts receiving more than one ASCT (n=69), only data on the first ASCT were included in the analysis. Pts treated with MEL140 and MEL100 were pooled (MELRed group).ResultsOf 187 ASCTs, 163 were performed as first-line and 24 as salvage therapies. Median follow up of the entire population was 77 months (range 3-172). Induction treatment included at least 1 novel agent (immunomodulatory drugs, IMiDs or proteasome inhibitors, PI) in 119 pts, whilst 68 pts received conventional chemotherapy. Median number of induction cycles before ASCT was 3 (range 1-10). Prior to ASCT 31 pts (17%) had achieved at least a very good partial remission (VGPR). MEL200 was used in 112 (60%) and MELRed in 75 pts (40%, 72 MEL140 and 3 MEL100). There was no difference in the two groups in the number of transplant performed as first line or as salvage therapy (p=0.54), as well as in the rate of pts achieving at least a VGPR before ASCT (17% vs. 16%, for MEL200 and MELRed respectively, p=0.84). More pts treated with MEL200 received induction treatment containing novel agents (70% vs. 55% for MEL200 and MELRed respectively, p=0.037). High quality responses (≥VGPR) after ASCT were higher in the MEL200 group: 89% of pts treated with MEL200 vs. 73% of those receiving MELRed, p=0.005. The main reasons for MEL dose reduction were older age (40%) and renal insufficiency (29%). Median age (range) and creatinine values (range) were 55 (35-68) vs. 63 (47-70) years (p<0.001) and 73 (51-186) vs. 90.5 (51-1022) μmol/l (p<0.001) for MEL200 and MELRed, respectively. More pts in the MELRed group had a Charlson Comorbidity Index (CCI) >2 (83% vs. 99% for MEL200 and MELRed respectively, p=0.001). Toxicities and duration of hospitalization of the two groups are depicted in Table 1. The higher response rate seen in pts treated with MEL200 translated in a longer median PFS (43 vs. 27 months for MEL200 and MELRed respectively, p=0.023) and OS (66% vs. 51% at 5 years for MEL200 and MELRed respectively, p=0.046). Multivariate analysis included CCI >2, response before and after ASCT ≥VGPR, disease stage at ASCT, age >65 years, treatment with new drugs, glomerular filtration rate ≥60 ml/min at the time of ASCT and treatment with MEL200. Disease stage (HR 0.57, 95% CI 0.331-0.978, p=0.041) and MEL200 (HR 0.49, 95% CI 0.295-0.802, p=0.005) were associated with an improved PFS, whilst none of the above mentioned variables had an impact on OS.ConclusionIn comparison with MELRed, MEL200 provides favorable responses and improves PFS and OS with only moderate increase of toxicity in this retrospective pts cohort. At least in pts treated with standard-induction therapy, MEL200 should be considered the standard conditioning regimen for ASCT eligible MM pts. DisclosuresBrioli:Janssen: Honoraria; Celgene: Honoraria, Other: Travel support, Research Funding. Mügge:Amgen: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria, Research Funding. Scholl:Abbivie: Other: Travel support; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Travel support; Deutsche Krebshilfe: Research Funding; Alexion: Other: Travel support; MDS: Other: Travel support; Carreras Foundation: Research Funding. Hilgendorf:Novartis: Other: Travel support, Research Funding; Medac: Other: Travel support, Research Funding. Sayer:RIEMSER Pharma GmbH: Honoraria. Ernst:Novartis: Research Funding. Hochhaus:Incyte: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding. von Lilienfeld-Toal:Takeda: Honoraria, Other: Travel support, Research Funding; Novartis: Honoraria, Other: Travel support, Research Funding; Celgene: Honoraria, Other: Travel support, Research Funding; Janssen: Honoraria, Other: Travel support, Research Funding.

Therapy-Related Myeloid Neoplasms Following Autologous Stem Cell Transplantation: The Prevalence of Chip Mutations at Time of Transplantation — a Single Center Experience

Introduction: Therapy-related myeloid neoplasms (tMN) are high-risk conditions evolved after exposure to a number of agents, including cytotoxic therapy, and include myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN). As such cytoreduction as part of autologous stem cell transplantation (ASCT) increases the risk of developing tMN. Importantly, both the use of ASCT and the incidence of tMN are rising. The recent characterization of clonal hematopoiesis of indeterminate potential (CHIP) has, in preliminary reports, been shown to increase the risk of developing de novo hematological disease as well as tMN. We hypothesized that patients with non-myeloid primary disease who develop tMN after ASCT, had detectable myeloid mutations at time of transplantation, and that these may represent a risk factor in the development of tMN. This study characterizes tMN patients previously subjected to ASCT and investigates whether CHIP mutations are present in hematopoietic stem cells at time of ASCT.Methods: The cohort of this observational study consists of patients treated with ASCT at the Department of Hematology, Aarhus University Hospital (Denmark) from 1989 to 2016. Cases were identified via the Danish Pathology Registry and all tMN diagnoses were verified by the same experienced hemopathologist (GBK). Only cases from patients with non-myeloid primary disease, who were diagnosed with tMN after being treated with ASCT (minimum latency being 90 days) were included. 36 cases with available leukapheresis products were identified out of a cohort of 1130 patients.Samples collected from leukapheresis prior to ASCT were subjected to targeted next-generation sequencing (NGS), using the commercially available panel “Myeloid Solution” (Sophia Genetics, Saint Sulpice, Switzerland), covering 30 genes relevant for myeloid neoplasms, joined with a bioinformatics pipeline from Sophia Genetics. Samples from 31 patients have been subjected to NGS. Variants residing in or within ± 25 nucleotides of coding exons and with coverage >5000 at the variant site were reported. Indels present in polynucleotide stretches were excluded.Data for continuous variables age, latency to tMN and survival were analyzed as one sample from a normal distribution based on the Students t-test. Normality was assessed via Q-Q plot. Estimates are reported with a 95% confidence intervals (Stata, version 15.1, StataCorp LLC, TX, USA).Results: The cohort consisted of 25 males (80.7%) and 6 females (19.3%), with an estimated median age at ASCT of 58 years (CI 95% 54;63). Estimated median time to tMN was 3.7 years (CI 95% 2.5;5.4) and estimated median survival after tMN diagnosis was 132 days (CI 95% 71;246). At time of tMN diagnosis, 14 patients had a poor risk karyotype and 9 patients had intermediate risk karyotype (hereof 4 normal karyotype). Karyotype was not evaluated in 8 patients.CHIP mutations were detected in stem cell enriched leukapheresis products from 21 patients (67.7%). Of these, we found multiple mutations in 14 patients (66%) and in one patient as many as 6 CHIP mutations. Point mutations were frequently found in the DNMT3A gene and was present in 16 out of 21 patients (76%). Six patients had more than one DNMT3A mutation, one of which had 5 separate DNMT3A mutations. Other mutations detected were TP53 (6/21), TET2 (5/21), ASXL1 (4/21), EZH2 (1/21), WT1 (1/21), JAK2 (1/21), NRAS (1/21), HRAS (1/21), BRAF (1/21), CSF3R (1/21), SF3B1 (1/21), ZRSR2 (1/21), CALR (1/21), SRSF2 (1/21).Conclusion: We found that CHIP mutations can be detected at time of ASCT in patients being treated for non-myeloid diseases. We hypothesize that presence of CHIP mutations at ASCT may predict the development of tMN and as such serve as a biomarker in this setting. We speculate that high-dose cytotoxic therapy may provide an evolutionary advantage for hematopoietic clones containing CHIP mutations. On the other hand, we cannot rule out that the cytoreduction administered prior at ASCT may be a main contributor to the tMN development. To address this as well as the development of tMN in the post-ASCT phase, a nested case-control study will be necessary. DisclosuresNo relevant conflicts of interest to declare.

Safety of Autologous Stem Cell Transplantation in Patients with Known HTLV-1 Infection: A Case Series of 4 Patients

Human T-cell lymphotrophic virus types 1 and 2 (HTLV-1/2) are delta retroviruses endemic to the Caribbean and Japan (Gessain et al., 2013). They are known to cause adult T-cell lymphoma-leukemia (ATLL) and tropical spastic paraparesis/HTLV-1 associated myelopathy (HAM) (Mahieux et al., 2003). Given the link between immunosuppressive states and development of lymphoproliferative disorders, there is hesitation on the behalf of clinicians to offer stem cell transplantation to patients who test positive for HTLV-1/2 antibody. We reviewed four cases of patients who underwent autologous stem cell transplantation (ASCT) at our institution after having tested positive for HTLV-1/2 antibody (Table 1). The median patient age at the time of ASCT was 58 years (range, 51-60). Two patients tested positive for HTLV-1 antibody and two tested positive for HTLV-2 antibody. Two patients underwent ASCT for treatment of multiple myeloma, one for diffuse large B-cell lymphoma (DLBCL), and one for light chain amyloidosis (AL). The myeloma patients received standard induction therapy with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) or lenalidomide, bortezomib, and dexamethasone (RVD). The DLBCL patient received rituximab, ifosfamide, carboplatin, and etoposide (R-ICE), while the AL patient underwent ASCT without induction. Three patients underwent conditioning with high-dose melphalan (200 mg/m2; HDM) and the lymphoma patient received carmustine, cyclophosphamide, and etoposide (BCV). Median stem cell collection was 8.35 x 106 CD34+ cells per kg (range, 4.8 -30.7). The median follow-up for these patients from date of transplantation was 22.4 months (range, 7.3-38.6). Median time to neutrophil and platelet engraftment was 9.5 days (range, 8-10) and 10 days (range, 9-14) respectively. Among these four patients, none developed complications related to HTLV-1/2 infection during the follow-up period. Two patients had a post-transplant course complicated by febrile neutropenia, and one patient developed typhlitis. One patient died on day + 221 due to a recurrence of cholangiocarcinoma leading to liver failure, and the other three remained alive at the time of last follow-up. Our data provides support that testing positive for HTLV-1/2 does not preclude eligibility for ASCT. DisclosuresSloan:Stemline Therapeutics: Consultancy.

Safety and Efficacy Data for Combined Checkpoint Inhibition with Ipilimumab (Ipi) and Nivolumab (Nivo) As Consolidation Following Autologous Stem Cell Transplantation (ASCT) for High-Risk Hematological Malignancies — CPIT-001 Trial

Safety and Efficacy Data for Combined Checkpoint Inhibition with Ipilimumab (Ipi) and Nivolumab (Nivo) As Consolidation Following Autologous Stem Cell Transplantation (ASCT) for High-Risk Hematological Malignancies — CPIT-001 Trial

Clinical Outcomes in Multiple Myeloma Post-Autologous Transplantation-A Single Centre Experience.

There is paucity of data from developing countries on the clinical outcomes in myeloma post-autologous transplantation. In this retrospective study, we used hospital records to retrieve data of patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) from January 1995 to December 2014 at our centre. During the study period, 245 patients underwent ASCT for myeloma. Of these, 19%, 37% and 37% were in complete response, very good partial response and partial response respectively at the time of ASCT. Only in 14 (5.7%) patients, the stem cells were cryopreserved. The transplant related mortality was 2.86%. The median follow up was 40.7 months (range 0-237.4 months). The 5-year overall survival (OS) and progression-free survival (PFS) for the entire cohort was 61.6% ± 3.8% and 37.2% ± 3.9% respectively. Independent predictors of OS included mononuclear cell dose infused, pre- and post-transplant response; and the use of maintenance therapy. Independent predictors of PFS included age at diagnosis, pre- and post-transplant response; and the use of maintenance therapy. In a resource limited setting, ASCT for myeloma is associated with low transplant related mortality. Pre- and post-transplant response and maintenance therapy are predictors of survival.

Abstract 2954: Immunomodulator maintenance post autologous stem cell transplant predicts better outcome in multiple myeloma patients with clonal hematopoiesis of indeterminate potential

Abstract Introduction: Multiple Myeloma (MM) is a clonal plasma cell malignancy, accounting for 10% of all hematological malignancies. Genetic analyses of large populations revealed that blood-specific somatic mutations in hematopoietic stem cells (HSCs) are commonly acquired during aging, a new entity labeled: clonal hematopoiesis of indeterminate potential (CHIP). We sought to determine the role of CHIP on survival of MM patients, specifically those receiving immunomodulators (IMiDs) maintenance (Lenalidomide or Thalidomide) post autologous stem cell transplant (ASCT). Methods: We tested cryopreserved HSCs of 629 MM patients who underwent ASCT between 2003 and 2011 at the Dana-Farber Cancer Institute. We used a target bait panel of 224 genes and performed deep-targeted sequencing at 978x coverage and ultra-low pass whole-genome sequencing at 0.1x to account for tumor contamination. Sequencing data was analyzed using ichorCNA, MuTect, and Strelka and mutation annotations were based on reported mutations in the literature and databases (ClinVar, COSMIC, cBioPortal, TCGA, and ExAC). Results: Our cohort had a median age of 58 years [24-83] at time of ASCT and median follow up post ASCT of 8 years [0.1-14.5]. 24% of patients had CHIP at time of ASCT, which is statistically similar to the 30% reported in non-Hodgkin's lymphoma (NHL), (Gibson et. al, JCO, 2017). The most commonly detected mutated genes were DNMT3A, TET2, TP53 and ASXL1. Acquiring mutations positively correlated with age (p=0.004). In contrast to NHL, PPM1D was not significantly mutated in MM (40% vs. 3.3%). 27 patients (4.3%) developed a second hematological malignancy at median of 4 years [1-10] post ASCT, of which 10 had CHIP. 22% received at least 3 years [0.06-12.8] of IMiD maintenance. Among those who did not receive IMiD maintenance, CHIP was associated with worse progression free survival (PFS) (p=0.047) where PFS at 3 years post ASCT was 31% (95%CI: 25-38) for those without CHIP vs. 15% with CHIP (95%CI: 7-25). In patients with IMiD maintenance, CHIP had no effect on PFS or overall survival (OS) (p=0.9). In patients with CHIP, receiving IMiD was associated with a better OS and PFS below the age of 58 and better PFS only in those above 58. In the overall cohort, CHIP was not associated with more adverse outcomes, which could be attributed to low OS and PFS in MM or the use of IMiD in 56% of this cohort. IMiD maintenance was associated with better OS (p&amp;lt;0.001) and PFS (p&amp;lt;0.001), consistent with prior studies, even in the presence of CHIP mutations. Conclusion: CHIP is a common entity among MM patients that predicts a worse PFS in those who do not receive IMiD maintenance therapy post ASCT. The use of IMiDs abrogated the deleterious effect imposed by CHIP in this cohort. Larger cohorts with longer follow up are needed, especially in the era of novel agents and long-term use of Lenalidomide maintenance. Citation Format: Tarek H. Mouhieddine, Jihye Park, Robert Redd, Christopher J. Gibson, Salomon Manier, Amin Nassar, Kalvis Hornburg, Marzia Capelletti, Daisy Huynh, Romanos Sklavenitits Pistofidis, Mark W. Bustoros, Saud H. AlDubayan, Brendan Reardon, Cody J. Boehner, Henry Dumke, Chia-Jen Lui, Darlys Schott, Eliezer M. Van Allen, Robert L. Schlossman, Nikhil C. Munshi, Kenneth C. Anderson, David P. Steensma, Jacob P. Laubach, Paul G. Richardson, Jerome Ritz, Benjamin L. Ebert, Robert J. Soiffer, Donna Neuberg, Irene M. Ghobrial. Immunomodulator maintenance post autologous stem cell transplant predicts better outcome in multiple myeloma patients with clonal hematopoiesis of indeterminate potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2954.

The evolution of stem-cell transplantation in multiple myeloma.

Autologous stem-cell transplantation (ASCT) remains an integral part of treatment for previously untreated, and may have value in the treatment of relapsed patients with, multiple myeloma (MM). The addition of novel agents like immunomodulators and proteasome inhibitors as induction therapy before and as consolidation/maintenance therapy after ASCT has led to an improvement in complete response (CR) rates, progression-free survival (PFS) and overall survival (OS). With advances in supportive care, older patients and patients with renal insufficiency are now able to safely undergo the procedure. The data concerning the timing of ASCT (early in the disease course or at first relapse), single versus tandem (double) ASCT and the role and duration of consolidation and maintenance therapy post ASCT remain conflicting. This review aims to discuss the evolution of stem-cell transplant over the past 3 decades and its current role in the context of newer, safer and more effective therapeutic agents.

170 - Characteristics, Time Trend and Outcomes of Patients Undergoing Autologous Stem Cell Transplant for Multiple Myeloma

Autologous stem cell transplant (ASCT) is an integral part of multiple myeloma (MM) treatment and recommended after induction therapy for responding eligible patients. Studies show equivalent outcomes of ASCT performed later than first response (delayed transplant), but the timing of ASCT in these analyses has been heterogeneous. Modern therapies of MM lead to excellent responses and many patients and physicians choose a delayed transplant approach. The difference in outcomes of ASCT specifically after first or second line anti-MM therapy has not been established. To address this question, we retrospectively reviewed the experience at our center. Patients undergoing ASCT for MM between 2004 and 2016 were studied. Information regarding patient and disease characteristics, pre-ASCT treatments, and outcomes was extracted by chart review. Patients were analyzed in two groups—those receiving 1 line (L1) versus 2 lines (L2) of therapy before ASCT. Data were summarized and variables compared between the 2 groups using appropriate statistics. Kaplan-Meier method was used to estimate survival probabilities. Between 2004 and 2016, 260 patients received ASCT for MM. Median age 61 yrs (range: 28-76), 55.8% were males. ISS stage was 1, 2 and 3 in 40%, 26% and 34%, respectively. MM risk category was high, intermediate and standard (mSMART criteria) in 9.2%, 19.7% and 71%, respectively. L1 group had 187 (72%) patients while L2 had 73 (28%). Patient age, sex, MM type (IgG, IgA or light-chain), ISS stage, risk category and transplant conditioning regimen were similar in the two groups (data not shown). Median time form diagnosis to ASCT was 210 days (range: 80-1064) for L1 and 392 days (range: 121-2321) for L2. Reasons for L2 therapy included progression after initial response to L1 (57%), refractory to L1 (19%), intolerable side effects (17.5%) and inadequate response (5.5%). L2 patients were more likely to have received an immunomodulatory drug (IMiD) and a proteasome inhibitor prior to ASCT than L1 patients (72% vs 28%, P < .001). Patients transplanted after 2010 were more likely to have received both IMiD and PI versus those transplanted earlier (49% vs 27%, P = .001). Median survival of L1 and L2 was 9.4 yr vs. 7.6 yr (P = .83) (Figure 1). Treatment with IMiDs and/or PI pre-transplant was associated with better survival versus no prior exposure to these agents but this was not statistically significant (P = .11) (Figure 2).Figure 2Survival after ASCT of patients who received IMiD and/or PI versus neither as pre-transplant therapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In this analysis, we show that a significant number of patients undergo delayed ASCT for MM. Outcomes of ASCT after L1 and L2 were similar. This being a retrospective study, we cannot asses the number of patients who intended to but were not able to undergo delayed ASCT. Exposure to one or both highly active anti-myeloma agents (IMids and PI) before ASCT was associated with better post transplant outcomes.

HBsAg-Negative, Anti-HBc-Negative Patients Still Have a Risk of Hepatitis B Virus-Related Hepatitis after Autologous Stem Cell Transplantation for Multiple Myeloma or Malignant Lymphoma.

PurposeAlthough hepatitis B surface antigen (HBsAg)–negative, hepatitis B core antibody (anti-HBc)–negative patients are not considered to be at risk for hepatitis B virus (HBV)–related hepatitis, the actual risk remains to be elucidated. This study aimed to evaluate the risk of HBV-related hepatitis in HBsAg-negative, anti-HBc–negative patients receiving autologous stem cell transplantation (ASCT) for multiple myeloma (MM) or malignant lymphoma.Materials and MethodsWe retrospectively reviewed data from 271 HBsAg-negative patients (161 anti-HBc–negative and 110 anti-HBc–positive at the time of ASCT) who received ASCT for MM or lymphoma. The risk of HBV-related hepatitis was analyzed according to the presence of anti-HBc. HBV serology results at the time of ASCT were compared with those at the time of diagnosis of MM or lymphoma.ResultsThree patients (two anti-HBc–negative MMs and one anti-HBc–positive MM) developed HBV-related hepatitis after ASCT. The rate of HBV-related hepatitis did not differ among patients with or without anti-HBc status (p=0.843). HBV-related hepatitis more frequently occurred in MM patients than in lymphoma patients (p=0.041). Overall, 9.1% of patients (16.7% with MM and 5.4% with lymphoma) who were HBsAg–negative and anti-HBc–positive at the time of diagnosis had lost anti-HBc positivity during chemotherapy prior to ASCT.ConclusionOur data suggest that HBsAg-negative, anti-HBc–negative patients at the time of ASCT for MM or lymphoma still might be at a risk for HBV-related hepatitis.

Stem Cell Transplantation in Multiple Myeloma.

High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains the standard of care for patients younger than 65 years of age with multiple myeloma (MM). However, this therapeutic approach has undergone substantial advances in this last decade, mainly due to the introduction of new drugs such as thalidomide, lenalidomide and bortezomib. These new drugs, in different combinations, have shown to significantly increase response rates after induction therapy and ASCT. Moreover, the positive results obtained with these agents in consolidation and maintenance strategies after ASCT strongly support the concept of continuous therapy, whose ultimate goal is the long-term control of the disease and the improvement of outcome. Preliminary data from studies investigating next generation proteasome inhibitors, such as carfilzomib and ixazomib, used upfront as well as at subsequent therapeutic lines, demonstrate the possibility of achieving molecular remission in most of the patients. The deeper responses obtained with new drugcombinations questioned the role of ASCT, and large, ongoing, phase 3 trials will shed light on the role and the timing of ASCT.

The role of stem cell transplant for lymphoma in 2017.

The role of stem cell transplant for lymphoma in 2017.

Outcome after autologous transplantation in the terms of comorbidity for patients with lymphoproliferative diseases: Single center experience.

e19502 Background: Autologous stem cell transplantation (ASCT) improves survival in patients with myeloma and lymphoma but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and overall survival (OS) in patients undergoing ASCT. Methods: We analyzed outcomes of 220 patients after high-dose melphalan and high –dose anti lymphoma chemotherapy during year 2000 to 2015. Individual comorbidities were prospectively collected at the time of ASCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. Results: HCT-CI score was 0, 1, 2, 3, and &gt;3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score &gt; 2 (26%). Higher HCT-CI was associated with lower KPS &lt; 90 (33% of subject’s score of 0 versus 50% in HCT-CI score &gt; 2). HCT-CI score &gt; 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohorts). One-year NRM was low at 2% (95% confidence interval, 1% to 4%). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score &gt; 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Factors that affect OS in the autologous recipients among lymphoma and myeloma patients were: HCT-CI, Karnofsky score, number of CD34+ cells/kg and time from diagnosis until transplant (p&lt;0.05). Factors that affect TRM/NRM were HCT-CI, ECOG, Karnofsky score and number of hospital days and body weight.(p&lt;0.05). Conclusions: ASCT for MM and lymphoma is associated with low NRM, and death is predominantly related to disease progression. Comorbidity evaluation during autologous transplantation for lymphoproliferative diseases can be a useful tool in predicting transplant outcome.

Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for Lymphoma.

Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition characterized by somatic mutations in the blood of otherwise healthy adults. We hypothesized that in patients undergoing autologous stem-cell transplantation (ASCT) for lymphoma, CHIP at the time of ASCT would be associated with an increased risk of myelodysplastic syndrome and acute myeloid leukemia, collectively termed therapy-related myeloid neoplasm (TMN), and other adverse outcomes. Methods We performed whole-exome sequencing on pre- and post-ASCT samples from 12 patients who developed TMN after autologous transplantation for Hodgkin lymphoma or non-Hodgkin lymphoma and targeted sequencing on cryopreserved aliquots of autologous stem-cell products from 401 patients who underwent ASCT for non-Hodgkin lymphoma between 2003 and 2010. We assessed the effect of CHIP at the time of ASCT on subsequent outcomes, including TMN, cause-specific mortality, and overall survival. Results For six of 12 patients in the exome sequencing cohort, mutations found in the TMN specimen were also detectable in the pre-ASCT specimen. In the targeted sequencing cohort, 120 patients (29.9%) had CHIP at the time of ASCT, which was associated with an increased rate of TMN (10-year cumulative incidence, 14.1% v 4.3% for those with and without CHIP, respectively; P = .002). Patients with CHIP had significantly inferior overall survival compared with those without CHIP (10-year overall survival, 30.4% v 60.9%, respectively; P < .001), including increased risk of death from TMN and cardiovascular disease. Conclusion In patients undergoing ASCT for lymphoma, CHIP at the time of transplantation is associated with inferior survival and increased risk of TMN.