tbuckley/cabot-search huggingface dataset:
Influence of polymorphisms discovered in cell-based model of cytarabine sensitivity on outcome in pediatric AML: A Children's Oncology Group Study.
Authors: Christine L. Phillips, Adam Lane, Gretchen Radloff, Robert B Gerbing, Todd Allen Alonzo, Beverly Lange, Alan S. Gamis, Christine M. Hartford, M. Eileen Dolan, Stella Davies
Journal: Journal of Clinical Oncology (2014)

10040 Background: Genetic variability of patients with AML contributes to the success and tolerability of cytarabine-based therapy. Methods: We investigated 120 genetic polymorphisms (SNPs) associated with cytarabine sensitivity (p<0.0001) that were discovered in a previous cell-based genome wide association study using Hap Map lymphoblastoid cell lines. We tested these variants for impact on outcome in 412 children with de novo AML treated on Children’s Oncology Group protocols, CCG 2941 and 2961. Therapy consisted of intensive cytarabine based induction and a randomization to consolidation with different cumulative doses of cytarabine; IDA-DCTER (3200 mg/m2) or IDA-FLAG (9190 mg/m2) in 2961. Results: The homozygous variant genotypes of rs 2025501 and rs 6661575 had increased in vitro cytarabine sensitivity and were also associated with increased treatment related mortality (TRM). TRM was most markedly increased in children randomized to the high dose cytarabine arm IDA-FLAG (rs 2025501: TRM 29 ± 7 % AA vs. 8 ± 3% GA, 17 ± 6% GG, p= 0.007 and rs 6661575: TRM 60 ± 20% T/T vs. 14 ± 5% C/T, 14 ± 4% CC, p=0.011) compared to the IDA-DCTER arm where no significant differences were observed. Improvement in three-year cumulative incidence of relapse was not statistically significant for either variant genotype. These SNPs are intragenic, but search in relevant databases indicate they are eQTLs with influence on expression of other genes. Conclusions: These findings warrant further exploration and validation in an independent dataset, but suggest cytarabine sensitivity genotypes may predict treatment related mortality and could be used to stratify to standard vs. high dose cytarabine regimens. rs 2025501 1-year cumulative incidence of TRM TRM randomized to IDA-FLAG arm 3-year relapse rate (RR) % deaths ± 1 SE % deaths ± 1 SE RR ± 1 SE =G/G 21 ± 5 % 17 ± 6 % 43 ± 5 % G/A 11 ± 3 % 8 ± 3 % 39 ± 4 % A/A 23 ± 5 % 29 ± 7 % 28 ± 5 % p value 0.048 0.007 0.184 rs 6661575 1-year cumulative incidence of TRM TRM randomized to IDA-FLAG arm 3-year (RR) % deaths ± 1 SE % deaths ± 1 SE RR ± 1 SE C/C 15 ± 3 % 14 ± 4 % 38 ± 3 % C/T 19 ± 4 % 14 ± 5 % 38 ± 6 % T/T 50 ± 20 % 60 ± 26 % 12 ± 13 % p value 0.011 0.011 0.482
Multicenter phase II trial of neoadjuvant carboplatin, weekly nab-paclitaxel, and trastuzumab in stage II-III HER2+ breast cancer: A BrUOG study.
Authors: Natalie Faye Sinclair, Bachir Joseph Sakr, Maysa M. Abu-Khalaf, George Somlo, Robert C Black, Gina G. Chung, Tina Rizack, Rochelle Strenger, Mary Anne Fenton, Michael DiGiovanna, Maria Constantinou, Donald R. Lannin, Robert Duffy Legare, Anees B. Chagpar, Sundaresan T. Sambandam, Veerle Bossuyt, Kayla Rosati, Lyndsay Harris, William M. Sikov
Journal: Journal of Clinical Oncology (2013)

619 Background: Patients (pts) with human epidermal growth factor receptor-2 amplified (HER2+) breast cancers (BrCa) who achieve a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) + trastuzumab (T) have an excellent prognosis (Cortazar, SABCS 2012). We tested a novel NAC + T regimen, designed to avoid potential cardiac and other toxicities associated with anthracyclines (A) and eliminate steroid premedication by replacing standard paclitaxel with nab-paclitaxel (nP). Methods: Clinical stage IIA-IIIC HER2+ BrCa pts received single agent either nP or T, with research biopsies and MRIs obtained before and after, then carboplatin (Cb) AUC 6 q3wks, nP 100 mg/m 2 and T 2 mg/kg weekly x 18 wks. If present, residual tumor was collected at surgery. Post-op pts complete a year of T; other adjuvant treatment is at MD discretion. Endpoints include clinical + pathologic response (pCR is defined as no invasive BrCa in breast + axillary nodes), residual cancer burden (RCB), treatment delivery and toxicities. Results: 53 pts (of 60 planned) are evaluable for response, median age 51 (34-72). Median delivered dose intensity for nP was 89 mg/m 2 /week; nP doses were omitted or reduced for neutropenia (ANC) (in 20% of pts) and neurotoxicity (Nt) (5%). Cb was reduced for thrombocytopenia (tcp) in 15%. Grade 3-4 toxicities: ANC 65%, tcp 22%, anemia 37%, Nt 7%. Serious adverse events: febrile neutropenia (5 pts), infections w/o neutropenia (4), vomiting, diarrhea or dehydration (7), thrombosis (2). LVEF fell by &gt;10% in 3 pts with no clinical CHF. Response data are tabulated below: 28 pts (53%) achieved pCR or RCB class I; 15/21 who did not received A-based adjuvant chemotherapy. Of 38 clinically node-positive pts, 26 (68%) were node-negative at surgery. Conclusions: The Cb/nP/T regimen was well tolerated, with pCR rates comparable to those reported with A-containing regimens. Final treatment and response data will be presented; correlative studies will be reported separately. Clinical trial information: NCT00617942. [Table: see text]
Contents, Vol. 27, 1976/77
Authors: Harold L. Levitan, Finn Askevold, Carl Fellner, Charles D. Kaplan, Michael Wogan, F. Berger, R. Rauskolb, M. Schütz, S. Stephanos, W.W. van der Schaar, Hoyle Leigh, James Ungerer, Adrian Ostfeld, Robert Drake, Morton F. Reiser, D. Beckmann, F. Berger, G. Leister, S. Stephanos, Harley C. Shands, Miguel A. Leibovich, Murray Cox, Caroline Cox, Rolf Adler, Jürg M. Herrmann, Nikolaus Schäfer, Thomas Schmidt, Othmar W. Schonecke, Thure v. von Uexküll, Stephen H. Armstrong, Mitchell Hendrix, C. Maggini, M. Guazzelli, P. Castrogiovanni, M. Mauri, G.F. de Lisio, S. Chierchia, G.B. Cassano
Journal: Psychotherapy and Psychosomatics (1976)
Three patients lose vision after unregulated stem cell treatment
Authors: Susan Mayor
Journal: BMJ (2017)

Three patients have developed severe vision loss in both eyes after undergoing intravitrial stem cell injections for age related macular degeneration (AMD) at a US clinic, a paper reviewing the cases has reported.1 The review authors have called for greater oversight of procedures using stem cells and the clinics providing these treatments and highlighted the need to increase public awareness of the “possibility of devastating outcomes” with unregulated treatment.

Several clinical trials are currently investigating the delivery of human retinal cells obtained from pluripotent stem cells to replace damaged cells. These trials are all …
Phase 1 study of ATR-101 in adrenocortical carcinoma (ACC): ATR-101-001.
Authors: Aung Naing, Mouhammed Amir Habra, Siqing Fu, Sarina Anne Piha-Paul, Marian Ijzerman, Joshua P Hein, Martin Phillips, David C. Smith
Journal: Journal of Clinical Oncology (2014)

TPS4607 Background: ATR-101 (Atterocor, Inc., Ann Arbor, MI, USA) is in clinical development for the treatment of adrenocortical carcinoma (ACC). ATR-101 is a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase). ACAT1 catalyzes cholesterol ester formation and, in the adrenals, is particularly important in creating a reservoir of substrate for steroid biosynthesis. ATR-101 is uniquely distributed to adrenal tissues and inhibition of adrenal ACAT1 by ATR-101 disrupts steroidogenesis and leads to selective apoptosis of steroid producing adrenocortical-derived cells. Similar effects have been seen in the human ACC cell line, H295R. ATR-101 has shown pre-clinical efficacy in H295R xenograft mouse models. ACC is an ultra-rare malignancy, occurring in about 2 per million population annually. ACC is frequently discovered in Stage 4 and the overall disease survival is approximately 17 months. Tumors often overproduce steroids normally produced in the adrenal cortex. Current therapies are toxic, difficult to administer, and poorly effective. Methods: ATR-101-001 is a phase 1, dose escalation “3+3” design study of ATR-101 in advanced ACC patients who have failed or declined standard therapy. The primary objectives are the safety and tolerability of once a day, orally administered ATR-101. Secondary objectives include the determination of MTD and pharmacokinetics, anti-tumor efficacy by RECIST, and evaluation of pharmacodynamic biomarkers, including steroid hormones and steroid intermediate production rates. Initial safety evaluation is after 28 days of therapy; subjects who appear to be deriving benefit may continue on ATR-101 indefinitely. The study is open at two centers in the United States to patients age 18 and over with advanced ACC. Patient’s mitotane level must be 5 ng/ml or less; the QTcF 470 ms or less; and if present, CNS metastases must be treated and inactive. Clinical trial information: NCT01898715.
Impact of immune checkpoint protein expression in tumor cells and tumor infiltrating CD8<sup>+</sup> T cells on clinical benefit from PD-1 blockade in metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Jean-Christophe Pignon, Opeyemi Jegede, Kathleen M. Mahoney, Raphael Brandao Moreira, Jesse Novak, Hilla Conen, Craig Norton, Lauren Christine Harshman, Eliezer Mendel Van Allen, Catherine J. Wu, Michael B. Atkins, Gordon J. Freeman, Paul J. Catalano, Toni K. Choueiri, David F. McDermott, Sabina Signoretti
Journal: Journal of Clinical Oncology (2017)

477 Background: PD-1 blockade with nivolumab has demonstrated efficacy in mccRCC patients who have failed prior therapy; however, durable benefit is observed only in a subset of patients. Correlative studies have demonstrated that tumor PD-L1 expression alone fails to reliably identify patients likely to benefit. Therefore, the development of more robust predictive markers is warranted. Methods: We studied 20 mccRCC patients treated with nivolumab (n=17) or atezolizumab (n=3) with distinct clinical outcomes: 8 pts who experienced durable clinical benefit (DCB) for ≥ 12 months and 12 pts with limited clinical benefit (LCB) for ≤ 6 months from start of therapy. Expression of PD-L1 and PD-L2 on tumor cells and density of tumor infiltrating CD8 + T cells and Foxp3 + cells were evaluated by immunohistochemistry. Percentages of tumor infiltrating CD8 + T cells expressing the immune-inhibitory molecules PD-1, TIM-3, or LAG-3 either alone or in combination were determined by multiplex immunofluorescence, using the Inform algorithm (Perkin Elmer). The association between clinical benefit (CB) and biomarker expression was assessed using Fisher exact test. Results: Baseline patient characteristics were similar in the DCB and LCB groups. When analyzed separately, tumor cell expression of PD-L1 or PD-L2 showed no association with CB. However, when positivity was defined as expression of either or both PD-L1(≥ 1% cutoff) and PD-L2 (≥ 5% cutoff), a significant association with CB was found (7/8 DCB vs 4/11 LCB, p = 0.04). A low percentage of tumor infiltrating CD8 + PD-1 + T cells co-expressing either or both TIM-3 and LAG-3 (75 th percentile cutoff) was also significantly associated with CB (8/8 DCB vs 7/12 LCB, p = 0.05). Conclusions: Our results suggest that expression of a PD-1 ligand on tumor cells (PD-L1 and/or PD-L2), and a low percentage of severely exhausted T cells, i.e. CD8 + PD-1 + T-cells co-expressing the immune-inhibitory receptors TIM-3 and/or LAG-3, might represent valuable predictive biomarkers for response to PD-1 blockade in mccRCC. Independent validation in a larger patient cohort is ongoing.
Clinical outcome of vertebral compression fracture after single fraction spine radiosurgery for spinal metastases.
Authors: Isabelle M. Germano, Andrea Carai, Seth Blacksburg, Puneet Pawha, yeh-Chi Lo, Sheryl Green
Journal: Journal of Clinical Oncology (2015)

e13017 Background: Vertebral compression fracture (VCF) may occur after stereotactic body radiation therapy (SBRT) for spine metastases. Recently, single fraction radiosurgery (sfSRS) is used more frequently. The aim of this study is to determine the clinical outcome of VCF after sfSRS. Methods: Spinal Instability Neoplastic Score (SINS) criteria were used to score 143 consecutive vertebral segments treated with sfSRS; mean delivery dose 17.6Gy. Follow-up MRI, pain, and neurologic assessments were obtained every 3-6 months. Pain was also scored at 7,14, and 30 days after SRS. Results: Follow up was 16+18 months, range 3-78. Long-term radiographic control occurred in 94% of cases. Pain improvement resulted within 7 days in 100% of cases with severe pain and sustained long-term in 95%. VCF occurred in 21% of segments: 30% were de novo VCF. The overall 1 year Fracture Free Probability (1yFFP) was 76%. Pre-existing VCF resulted in higher probability to progress: 1yFFP 90% vs 60%. Symptoms presented in 6% of cases with de novo VCF and 39% with progressive. The former were treated with vertebral augmentation (VA), the latter with open surgery. Surgery/VA prior to SRS did not change risk of progressive VCF. Univariate but not multivariate analysis identified histology (colorectal), pre-existing VCF, and pain (severe) as significant predictors of VCF. Conclusions: sfSRS compares favourably to SBRT for radiographic and pain control with similar VCF risk. Patients with pre-existing VCF have a higher probability to progress, become symptomatic, and require surgery. These results may help discussing risk and benefits with patients undergoing sfSRS for spinal metastasis and developing new treatment algorithms.
Baseline demographic characteristics and treatment patterns by cancer site of care: Physician office versus hospital outpatient.
Authors: Andrew M Howe, Stephen Stemkowski, Yong Li, Sari Hopson, Joseph Dye, Jeffrey Patton, Anthony Masaquel, Art Small
Journal: Journal of Clinical Oncology (2014)

e17536 Background: Chemotherapy infusion costs among different oncology sites of care may be due to patient demographic and utilization differences. We compared baseline demographic, clinical and healthcare (HC) costs between patients receiving chemotherapy or biologic infusions at independent physician office (PO) and hospital outpatient (HO) cancer treatment centers in the US. Methods: Claims data from Humana’s Commercial and Medicare health plan during 2007-2013 were used to identify continuously enrolled patients who received infusion therapy within 120 days post diagnosis for early stage breast (esBC), metastatic breast (mBC), metastatic colorectal (mCRC), metastatic lung (mLC) cancers, non-Hodgkin’s Lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Site of care codes were used to categorize patients by infusion therapy location. Patient demographic, cancer clinical characteristics and HC costs at baseline (6 month pre-index infusion) were summarized in each cohort. Results: A total of 19,589 patients were identified. The mean age between HO and PO cohorts was 66.1 (SD±11.4) vs. 66.9 (SD±11.6) (p<0.01). No difference in gender was observed (p=0.54). Mean Deyo-Charlson comorbidity index scores were statistically different (p<0.01) 6.0 (SD± 3.5) and 5.5 (SD±3.5) among patients in HO and PO settings. Overall, pre-index hospitalization was generally higher for HO, but pre-index HC costs and ER visits were not significantly different between the two cohorts. Conclusions: Overall, patient characteristics show relatively small differences between the populations. The direction and size of differences vary by disease type. Future research will examine differences in infusion utilization, HC costs, and quality of care among patients in PO and HO settings. N=19,589 Pre-index ER visit (p=0.31) Pre-index hospitalization (p=0.008) Pre-index mean total costs ($) (p=0.24) Cancer HO PO HO PO HO PO All 33.2% 32.4% 49.1% 46.9% 25,247 24,720 esBC 31.6% 18.8% 19.0% 36.2% 38.5% 18,977 20,006 mBC 14.2% 27.7% 28.7% 46.0% 42.7% 27,460 25,947 mCRC 11.8% 37.7% 40.4% 66.6% 64.4% 35,539 36,091 mLC 18.6% 46.4% 49.8% 62.3% 62.2% 27,351 29,633 NHL/CLL 24% 42.0% 36.5% 49.1% 41.8% 25,850 21,912
Blood-based genomic profiling of circulating cell-free tumor DNA (ctDNA) in 1397 patients (pts) with colorectal cancer (CRC).
Authors: John H. Strickler, Kimberly C. Banks, Rebecca J Nagy, Richard B. Lanman, AmirAli Talasaz, Ryan Bruce Corcoran, Scott Kopetz
Journal: Journal of Clinical Oncology (2017)

584 Background: ctDNA is shed into the bloodstream by tumor cells throughout the body, offering a non-invasive means of genomic testing, and a way to detect heterogeneous, subclonal genomic alterations present in distinct tumor lesions within an individual pt. However, a broad comparison of mutation prevalence in CRC ctDNA versus CRC tumor tissue has not yet been performed. Methods: ctDNA from 1397 CRC pts was analyzed using a CLIA-certified digital sequencing assay (Guardant360, Guardant Health) capable of detecting single nucleotide variants (SNV) in up to 70 genes, as well as selected insertions/deletions, amplifications, and fusions. Subclonal mutations were defined as mutations with mutant allele fractions (MAF) ≤ 50% of the greatest somatic MAF in the sample. Frequencies of mutations detected were compared to two large tissue-based sequencing databases (TCGA and NHS/HPS). Results: 1500/1772 (85%) tests had at least one genomic alteration (1397 unique pts). The most common SNV mutations included TP53 (62%), APC (47%), KRAS (39%), PIK3CA (17%), EGFR (11%), SMAD4 (11%), and BRAF (11%); these frequencies were comparable to rates in TCGA and NHS/HPS. In contrast, EGFR extracellular domain (ECD) mutations (42 pts) and JAK2 V617F mutations (16 pts) detected in ctDNA were not seen in tissue sequencing, reflecting acquired resistance to EGFR antibodies and clonal hematopoiesis of indeterminate clinical potential, respectively. 88% of pts with ECD mutations had at least one additional non-ECD resistance alteration detected in ctDNA (range 1-9, median 2.6), including KRAS, NRAS, BRAF, MAP2K1, MET and ERBB2. EGFR mutations were most likely to be detected as subclonal (86%), while mutations most likely to be clonal included KRAS (71%), TP53 (65%), BRAF (65%), and APC(63%). In 84 pts with serial monitoring, 87% had either gain (61%) or loss (63%) of clones over time. Conclusions: Blood-based genomic profiling can effectively detect common genomic alterations in CRC at comparable frequencies as observed in tissue and provide novel insights into tumor clonality and clonal dynamics. Clinical trials to target EGFR ECD mutations may be limited by the multiplicity of resistance mechanisms in each pt.
Randomized phase II study of weekly paclitaxel with or without carboplatin followed by cyclophosphamide/epirubicin/5-fluorouracil as neoadjuvant chemotherapy for stage II/IIIA HER2-negative breast cancer.
Authors: Kenji Tamura, Jun Hashimoto, Hitoshi Tsuda, Masayuki Yoshida, Hideko Yamauchi, Kenjiro Aogi, Satoru Shimizu, Hiroji Iwata, Norikazu Masuda, Naohito Yamamoto, Kenichi Inoue, Shinji Ohno, Katsumasa Kuroi, Tamie Sukigara, Yasuhiro Fujiwara, Masashi Andoh
Journal: Journal of Clinical Oncology (2014)

1017 Background: Platinum based neoadjuvant chemotherapy (NAC) in HER2-negative breast cancer (HNBC) has a potential to improve pathological complete response (pCR). We evaluated the efficacy and safety of carboplatin (CBDCA) and weekly paclitaxel (wPTX) followed by cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as NAC for HNBC. Methods: Patients with stage II-IIIA HNBC were randomly assigned to preoperatively CP-CEF arm (4 cycles of CBDCA [area under the curve 5 mg/mL. min, day 1, every 3 weeks] and wPTX [80 mg/m2, day 1, 8, 15, every 3 weeks] followed by 4 cycles of CEF [500/100/500 mg/m2, day 1, every 3 weeks], or P-CEF arm (4 cycles of wPTX followed by 4 cycles of CEF). The primary endpoint was pCR rate. Breast tumor tissues by preoperative biopsy were tested for Ki-67, EGFR, Cytokeratin (CK) 5/6, BRCA1, vimentin, ERCC1 and ZEB1 by immunohistochemistry (IHC). Results: Of 181 eligible patients, 89 were randomly assigned to the CP-CEF arm and 92 to the P-CEF arm. Two patients in each arm refused to receive NAC. Overall 88 patients in the CP-CEF arm and 91 patients in the P-CEF arm were assessable for efficacy and safety. The primary endpoint; pCR rate in the CP-CEF arm was significantly higher than that in the P-CEF arm (31.8 vs. 17.6%, p = 0.01). Among patients with triple-negative breast cancer (TNBC), the pCR rate in the CP-CEF arm was significantly higher than that in the P-CEF arm (61.2% vs. 26.3%, p = 0.003). Grade 3-4 neutropenia was observed in the CP-CEF arm more frequently than in the P-CEF arm (65.9% vs. 38.5%). We gained 46 tumor samples from the registered patients (26%). EGFR, CK5/6 and BRCA1 expressions were significantly frequent in TNBC. EGFR expression was significantly associated with pCR rate in the 46 patients (45.0% vs. 11.5%, P=0.010), and in patients in CP-CEF arm (63.8% vs. 18.2%, P=0.040), but not in patients in P-CEF arm. Conclusions: Adding CBDCA to neoadjuvant wPTX followed by CEF for HNBC statistical significantly improved pCR rate with a favorable safety profile. EGFR expression by IHC is a potent predictive biomarker of response to the CP-CEF regimen as NAC. Clinical trial information: 000003355.
Mild microwave activated, chemo-thermal combinational tumor therapy based on a targeted, thermal-sensitive and magnetic micelle
Authors: Wei-Shuo Li, Xiao-Juan Wang, Shuo Zhang, Jing-Bo Hu, Yang-Long Du, Xu-Qi Kang, Xiao-Ling Xu, Xiao-Ying Ying, Jian You, Yong-Zhong Du
Journal: Biomaterials (2017)
Epidemiologic model estimating number of Hodgkin lymphoma patients who relapsed after autologous stem cell transplant in the United States.
Authors: Andrew Lee, Adeline Abbe, Alaa Hamed, Frank Neumann, Robert Olivares, Anas Younes
Journal: Journal of Clinical Oncology (2013)

e12554 Background: Hodgkin Lymphoma (HL) is an uncommon lymphoid malignancy with an estimated 9,060 new cases and 1,170 patients dying of disease each year in the US. High dose chemotherapy followed by autologous stem cell transplant (ASCT) is standard treatment for relapsed or refractory HL. Patients who do not respond to or relapse after ASCT have a short survival and are candidates for investigational agents. In the absence of published studies, the primary objective of this study was to estimate the percent and number of patients with HL who relapsed after ASCT. Methods: Number of ASCT performed for HL patients and relapse rate reported in the literature was used to estimate number of HL patients who relapsed after ASCT. Number of ASCT in US with HL was extracted from 2008-2010 CIBMTR (Center for International Blood and Marrow Transplant Research) data assuming a stable number for 2010-2012. A literature review (1993-2012) using EMBASE identified relapse rate after ASCT in HL. A model was built using relapse rates at 12, 24, 36, 48 and 60 months. If there was no relapse rate at a time point, it was estimated by dividing nearest data point following relapse rate by period length. Rate differences at 12 and 24 months were used to estimate relapse rate for 2 nd year. Same methods were used to calculate other year rates. Results: An estimated 791 patients underwent ASCT for HL in 2012 based on prior years data. Three clinical trials and 9 epidemiological studies providing post-ASCT relapse rate were identified from the literature review. Relapse rates over 5 years and number of patients with relapsed HL after ASCT were estimated to be 44.7% and 352 patients, respectively, in 2012. Conclusions: : In the absence of published literature, a model was built to estimate the number of HL patients who relapsed after ASCT suggesting a high rate at 44.7% over 5 years. Because not all US centers participate in the CIBMTR registry, these numbers are likely to be conservative and actual rate may be higher. Clinical trials targeting this relatively small patient population with clear unmet medical need require collaborative efforts to enroll patients and more research to understand factors for patients relapsing post-ASCT.