bluuebunny/crossref_metadata_2025_split huggingface dataset:
The outcomes of allogeneic stem cell transplantation in AML patients with monosomal karyotypes.
Authors: Sohn Sang Kyun , Lee Soo Jung , Kim Jong Gwang , Chae Yee Soo , Kang Byung Woog , Moon Joon Ho , Baek Jin Ho 
Published: March 2020

6538 Background: The prognosis of acute myeloid leukemia (AML) with monosomal karyotype (MK) was reported extremely poor. We investigated the role of allogeneic stem cell transplantation (allo-SCT) for those with MK. Methods: A total of 114 patients who received allo-SCT for treatment of AML were retrospectively analyzed. All patients were treated with standard induction chemotherapy with anthracycline and cytarabine. Cytogenetic abnormalties were grouped according to recently published MRC criteria and MK was defined as at least two autosomal monosomies or one monosomy plus one or more structural abnormality. Results: Thirteen patients had favorable cytogenetic risk, 78 intermediate, 11 adverse without MK, and 12 adverse with MK at the time of diagnosis. Among 12 patients with MK, 5 (41.7%) achieved CR after induction therapy, 1 (8.3%) relapsed and 6 (50.0%) refractory at the time of allo-SCT. The 2-year overall survival (OS) was significantly lower for patients with MK (17.5%) compared to favorable (76.9%), intermediate (61.0%), and adverse without MK (36.4%, p=0.017). In the multivariate analysis, those with MK was related with extremely poor outcomes (HR 6.02, p=0.008), which was independent risk factor for OS. Survival benefit was observed in MK group with chronic GVHD compared to those without chronic GVHD. The median survival was 272 days with chronic GVHD (95% CI 204-339 days) compared to 159 days (95% CI 76-172 days) without chronic GVHD (p=0.010). Conclusions: The prognosis remained poor in patients with MK despite of allo-SCT. Innovative approaches to induce GLV effects are needed to improve SCT outcomes in patients with MK.
Effect of radioimmunotherapy-based conditioning for autologous stem cell transplantation on poor-risk molecular profiling in diffuse large B-cell lymphoma.
Authors: Siddiqi Tanya , Tsai Ni-Chun , Palmer Joycelynne , Forman Stephen J. , Krishnan Amrita Y. 
Published: March 2020

6547 Background: Gene expression profiling has improved risk stratification of diffuse large B-cell lymphoma (DLBCL) in the first line setting as shown by DNA microarray analysis and immunohistochemistry (IHC). 5-year overall survival (OS) for germinal center B-cell-like (GCB) DLBCL is significantly better than that for non-GCB DLBCL in newly diagnosed patients. However, in the relapsed/refractory setting, autologous stem cell transplant (ASCT) appeared to overcome the poor prognosis of cell of origin as defined by IHC using CD10, Bcl6 and MUM1 and there was no difference in survival between GCB and non-GCB groups. Ibritumomab tiuxetan (Z)-BEAM conditioning regimen for ASCT in DLBCL has produced promising response rates and progression free survival (PFS). The role of poor risk molecular markers in predicting outcome with the novel conditioning regimen Z-BEAM is unknown. Methods: We evaluated cell of origin (GCB, non-GCB) using IHC in 36 patients undergoing ASCT with Z-BEAM conditioning from 2002 to 2010. Median age of the patients was 54.5 years. There were 12 females and 24 males. 6 patients were in 1st CR/PR ( 17%), 12 had induction failure disease (33%), 9 were in 1st relapse (25%), 1 in 2nd relapse (3%) and 8 were in ≥2nd CR (22%). 27 patients had chemosensitive disease (75%) and all had prior rituximab exposure. Median number of prior treatments was 2. IPI at transplant was mainly low risk (78%). 22 patients had GCB (61%) and 14 (39%) had non-GCB DLBCL. Results: Median follow up is 25.6 months. 12 patients relapsed (33%) and 9 died (25%). The major cause of death is relapse/disease progression. At 2 years, median OS is 79% and median PFS is 64%. No significant difference in 2 year OS and PFS is noted between the GCB and non-GCB groups (p=0.07 and 0.06 respectively). Conclusions: Z-BEAM conditioning for ASCT may overcome the poor prognostic effect of non-GCB DLBCL in relapsed/refractory disease. Further evaluation of cell of origin using new markers like GCET1, LMO2 and FOXP1 could confirm these results as there seems to be better concordance of these markers with DNA microarray analysis.
Cost-effectiveness analysis of bendamustine plus rituximab versus CHOP-R in treatment-naive patients with mantle cell (MCL) and indolent lymphomas (IL).
Authors: Su Wayne , Quon Peter , Whalen John , Ranganathan Gayatri , Wronski Samantha , Mwamburi Mkaya , Knopf Kevin B. , Sterchele James A. , Salvador Christopher G. , Ozer Stillman Ipek , Kadambi Ananth 
Published: March 2020

6553 Background: To assess the cost-effectiveness of bendamustine plus rituximab (B-R) vs cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP‑R) for treatment-naive patients with MCL or IL from a US healthcare payer perspective. Methods: A discrete event simulation was developed for a mixed population of patients with MCL or IL. Two arms were simulated, each containing 1000 identical MCL or IL patients treated with B-R or CHOP-R. Input data for baseline characteristics, overall response, and risks for treatment-related adverse events (AEs) and infections were obtained from the NHL 1-2003 trial (n=549, primarily stage IV MCL and IL); gaps were filled by consultation with experts. Direct medical costs and utilities were estimated based on US databases and published literature. Costs and benefits were discounted at 3% per annum. Base case model predictions were performed by selecting regression models that had a best fit to progression free survival (PFS). Robustness of these models was evaluated by testing other models with reasonably good fit. Results: In the base case, model predicts longer PFS for B-R than for CHOP-R in MCL (average of 49.8 vs 28.6 months) and IL (67.9 vs 51.0). Quality-adjusted life-years (QALYs) per patient were higher for B-R than CHOP-R for MCL (3.51 vs 2.68) and IL (4.42 vs 3.58). For MCL, total per-patient costs were $115,191 for B-R and $100,261 for CHOP-R; for IL, respective costs were $134,814 and $110,065, resulting in incremental cost-effectiveness ratios (ICERs) for B-R vs CHOP-R of $18,161 per QALY for MCL and $29,549 for IL (ICER<$50,000 to be cost-effective). Higher complete and partial response rates for B-R than for CHOP-R impacted subsequent treatment costs, which were lower for B-R by $21,632 for MCL and $24,961 for IL, as well as AE costs, lower by $10,113 and $10,570, respectively. The model results were robust with respect to the use of alternative regression models for PFS estimation. Conclusions: In patients with MCL or IL, the model demonstrates that B-R is a cost-effective alternative to CHOP-R. Alternative regression models confirmed robustness of results. Support: Teva Pharmaceutical Industries Ltd.
An anthropometric study in children with chronic myeloid leukemia on imatinib.
Authors: Reddy Goteke Vamshi Krishna , Maddi Rahul Narayan , Thota Narender Kumar , Coca Pragnya , Nagalla Balakrishna , Linga Vijay Gandhi , Gundeti Sadashivudu , Digumarti Raghunadharao 
Published: March 2020

6554 Background: The long-term adverse effects, especially in children with chronic myeloid leukemia (CML) on imatinib are unknown. There is very little literature addressing the adverse effects on growth in children on imatinib. We analysed the effect of imatinib on anthropometry in children with CML. Methods: The records of children ≤ 18 years with CML diagnosed at our institute between 2003 and 2011 were retrospectively analysed. Children who received imatinib for at least one year and on regular follow up were eligible for growth assessment. The data was analysed using WHO AnthroPlus v1.0.4 and SPSS.v19 software and the Height for age and BMI for age/sex “z” scores were computed. Results: A total of 61 children were started on imatinib. But, only 37 children were eligible for assessment of growth. Of them 3 were further excluded as the WHO AnthroPlus software supported data only till 19 completed years. Median age was 12 years (range: 5 – 17). 17 children were in the prepubertal age (5-11years) at commencement of imatinib. The mean duration of imatinib therapy was 41.24 months (range: 12–91). The overall z- scores for height for age (HAZ) on follow up were significantly (p =0.029) lower, compared to baseline. However when analysed according to age groups, the HAZ was found significantly (p=0.005) lower among 5-11 year age group compared to age group of ≥12 years. No significant differences were observed in BMI for age/sex z scores by age groups, over the period. Conclusions: Imatinib appears to cause growth retardation in prepubertal children. Further follow up may shed more light on the degree of stunting and the deficit in the final adult height.
Treatment outcomes in patients older than age 60 with acute myeloid leukemia (AML) in the nonclinical trial setting.
Authors: Duffy Steven , Bains Puneet , Pavlovitz Brian , Vajpayee Neerja , Newman Nancy , Gajra Ajeet 
Published: March 2020

6572 Background: Optimal treatment of older adults with AML remains challenging. While AML tends to be a disease of older adults, this population experiences greater treatment-related toxicity and worse overall survival than younger patients. Only fit older adults enter clinical trials and thus the results may not apply to the entire population. Methods: We conducted a retrospective analysis of patients > 60 years with AML (APL excluded) diagnosed prior to 2008 with IRB approval. The association of clinical factors (age, sex, comorbidities, prior chemotherapy), leukemia (prior myelodysplastic syndrome or myeloproliferative neoplasm, cytogenetics, WBC count), and therapy (induction chemotherapy, palliative chemotherapy, and best supportive care) as they relate to overall survival was evaluated using bivariate and multivariate regression analyses. Results: Of 87 patients (median age 73), 45% were male, 58% had high risk cytogenetics, 38% had prior MDS/MPD, 92% were chemotherapy naive, and 21% were in the high/very high Charlson risk class. The majority (67%) received standard dose induction chemotherapy (IC), 9% received (palliative intent) low-dose chemotherapy (LDC), and 24% received best supportive care (BSC). The median overall survival (OS) of the entire cohort was 2.5 months. On bivariate analysis high WBC (>50,000 at presentation) was negatively associated (1.0 vs 2.7 months p <0.01) with survival. OS for IC, LDC, and BSC were 3.1, 2.8, and 0.7 months, respectively (p=0.001). On multivariable analysis, IC conferred longer survival when compared to LDC and BSC combined (OR 0.33 CI 0.2-0.6, p<0.001). High WBC was associated with a decreased survival time (OR 2.96 CI 1.6-5.5, p=0.02). Mortality during induction or consolidation chemotherapy was 38%. At 5-year follow-up, only 4 patients were alive. Conclusions: In a non-clinical trial setting, OS of older adults with AML remains dismal. While IC offers a chance of longer survival, mortality with IC is unacceptably high. Further studies are required to identify and validate tools for risk stratification in older adults with AML as well as to utilize therapies with an improved toxicity profile.
Outcome of acute myeloid leukemia in patients with a history of autoimmune disease.
Authors: Dinardo Courtney Denton , Ogdie Alexis R , Hexner Elizabeth O. , Frey Noelle V. , Loren Alison W. , Luger Selina M. 
Published: March 2020

6579 Background: Increased risks of solid and lymphoid malignancies are described in patients with autoimmune (AI) disease. The association between AI disease, AI treatment (particularly anti-TNF therapy), and AML is less established. Moreover, the pathologic characteristics of AML in this population have not been evaluated. Here we describe our AML experience in patients with prior AI disease. Methods: Patients with AML from 1992 to 2011 were identified from our database, and AI disorder was verified through chart review. Patients were included if they had an AI disorder that required systemic treatment, and diagnosed > 1 year prior to AML. Patients were excluded if details including the year of AI diagnosis or treatment(s) received were not documented. A total of 22 patients were included for analysis. Results: Median age at AML diagnosis was 59 years (range 32 – 78), 4 (18%) were men. 10 (48%) had received an anti-TNF agent, for a median duration of 30 months (range 2 – 120). Median latency from AI diagnosis to AML was 9.4 yrs. All FAB subtypes were represented except M0 and M6, 9 (41%) had M4 or M5 disease. 10/21 patients (45%) had normal cytogenetics, and 5 had favorable cytogenetics (2 with acute promyelocytic leukemia (APML)). Standard induction was given to 19 patients, and APML-directed therapy for those with APML. One patient received an autologous transplant in CR1, and 5 an allogeneic transplant (1 in CR1, 4 in CR2). 9 patients are alive in CR1. 13 relapsed, and 4 (31%) are alive in CR2 or CR3 (3 following allogeneic transplant in later CR). Median OS was 68.1 months. In univariate analysis, factors associated with OS were cytogenetics, FAB subtype, and gender. Anti-TNF therapy may be associated with poorer prognosis; this was not statistically significant. Median OS was 14.1 months for poor, 68.1 months for intermediate, and not reached for favorable risk cytogenetics. Conclusions: Median OS was higher (> 5 years) than expected. Younger age and an increased incidence of favorable risk AML may account for this finding: whether this is a meaningful biologic association or stochastic event can only be verified with larger studies. Our observations do not support a label of “secondary leukemia” or therapy-related neoplasm in this population.
A phase I/II trial of combination of PKC412 and 5-azacytidine (AZA) for the treatment of patients with refractory or relapsed (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
Authors: Nazha Aziz , Kantarjian Hagop , Borthakur Gautam , Kadia Tapan M. , Faderl Stefan , Ravandi Farhad , Estrov Zeev , Jabbour Elias , Quintas-Cardama Alfonso , Cortes Jorge E. 
Published: March 2020

6589 Background: Midostaurin (PKC412) is a FLT3 kinase inhibitor with activity in acute myeloid leukemia (AML). Hypomethylating agents play an important role in the treatment of AML and MDS. We investigated the safety (phase I) and clinical activity (phase II) of combination of 5-azacytidine (AZA) and PKC412 in pts with R/R AML and MDS. Method: Pts ≥18 years with MDS, CMML or AML, who failed prior therapies with performance status <2, adequate liver (bilirubin < 2x ULN, ALT ≤ 2.5x ULN) and renal (creatinine < 2x ULN) functions were eligible. Pts received AZA 75 mg/m2 subcutaneously or intravenously for 7 days of each cycle (Days 1-7) and PKC412 at 25 mg (cohort 1) and 50 mg (cohort 2; target dose) orally twice daily for 14 days (Days 8-21). Pts were to receive up to 12 cycles if benefit from treatment. Supportive care was standard. Results: 14 pts were included in phase I. 1 pt was inevaluable for DLT (withdrawal before completing cycle#1). 6 pts treated in cohort 1 and 7 in cohort 2. 1 pt in cohort 2 received PKC412 dose as per cohort 1 dose by pt error. Pt characteristics and responses are summarized in the Table. The overall response rate (ORR) was 3/13(21%) (2 with CRi, 1 pt dropped BM blasts form 27% to 7% after 2 cycles and went to transplant. 1/4 with FLT3-ITD achieved CRi, 2 of the non-responders received prior FLT3 inhibitors (1 had developed FLT3 D835). All toxicities were grade 1 (nausea 1 pt, vomiting 1 pt, dry skin 1 pt, and rash 1 pt) with no difference between the 2 groups. No DLT was identified. Conclusions: PKC412+AZA is safe and well tolerated at the intended doses with good ORR in high risk pts with R/R AML. Phase II study is enrolling pts with FLT3-ITD. Updated result will be presented. [Table: see text]
The large granular lymphocytic leukemia registry: A detailed analysis of 79 patients with LGL leukemia and rheumatoid arthritis.
Authors: Boughan Kirsten Marie , Loughran Thomas P. 
Published: March 2020

6590 Background: The purpose of this study is to analyze patients enrolled in the LGL leukemia registry to distinguish the similarities between LGL leukemia and rheumatoid arthritis in order to access overlapping immune mechanisms that may be responsible for neutrophil mediated destruction. Methods: A retrospective chart review was performed on 79 patients enrolled in the LGL registry at Penn State Cancer Institute. All patients enrolled in the study had a diagnosis of both rheumatoid arthritis and potentially LGL leukemia. Data was collected for age, sex, RF factor positivity, family history, autoimmune disease, T-cell receptor gene rearrangement, and bone marrow invasion. Results: Of 79 patients the mean age of onset for LGL leukemia was 60 years old with no discrepancy noted between sexes, 37 M, 42 F. 49 patients were positive for rheumatoid factor. 27 patients had rheumatoid arthritis in a first degree relative with no discrimination between maternal or paternal inheritance. 22 patients were positive for any other autoimmune process. 60 patients were positive for T-cell receptor gene rearrangement. Of the remaining 19 patients that were negative for T-cell receptor rearrangement, 12 had evidence of bone marrow invasion (CD3/CD8+ infiltrate in >20% bone marrow) and two showed bone marrow invasion of NK cell LGL (CD3/CD8-, CD57+) (Table). Conclusions: Patients with T cell LGL leukemia and rheumatoid arthritis appear to be clinically similar with regard to age, duration of disease, and other autoimmune disorders as patients with rheumatoid arthritis alone. Our patient population showed those with TLGL and RA also tends to have a positive family history of RA in up to 20% as opposed to 5-10% in RA patients. Given that RA and TLGL have a significantly higher expression of the HLA-DR4 haplotype than healthy patients, it is conceivable that with shared genetic alterations, and gene environment interactions that may promote posttranslational modification, there may be a loss of tolerance resulting in T cell activation, and eventual transformation into a T cell clone. [Table: see text]
Analysis of imatinib (IM)-related, low-grade (LG), non-hematologic (heme) adverse events (AEs) in patients (pts) with chronic myeloid leukemia (CML) switched to nilotinib (NIL): ENRICH study update.
Authors: Mauro Michael J. , Lipton Jeffrey Howard , Miller Carole Brennan , Ailawadhi Sikander , Busque Lambert , Akard Luke Paul , Pinilla-Ibarz Javier , Ericson Solveig , Lin Felice , Cortes Jorge E. 
Published: March 2020

6605 Background: This study update assesses change in chronic LG non-heme AEs in adult Ph+ CML-CP pts switched from IM to NIL. Methods: Pts were eligible if treated with IM 400 mg/d for ≥3 mo, and had IM-related grade (G) 1/2 non-heme AEs persisting ≥2 mo or recurring ≥3 times and persisting despite best supportive care. Pts received NIL 300 mg BID. Primary endpoint is change in IM-related LG non-heme AEs at 3 mo. Disease response was monitored by RQ-PCR and pt-reported outcomes measured by 2 quality-of-life (QoL) questions and MD Anderson Symptom Inventory (MDASI)-CML. Results: 47 pts were enrolled as of data cut-off (11/14/2011). There were 168 baseline IM-related non-heme AEs: 121 G1, 47 G2. 37 pts completed 3 mo NIL, by 3 mo 103 of 154 IM-related AEs (67%) improved (92 resolved, 11 improved from G2 to G1), 47 unchanged, 4 increased in severity. 13 pts were dose reduced for NIL-related AEs; 8 pts re-escalated after AEs recovered to G1 or resolved. 34 G3 AEs occurred in 15 pts; investigators reported 19 AEs as suspected NIL-related (increased bilirubin, lipase, or blood glucose; hypokalemia; hypophosphatemia; pruritus; bronchitis; dehydration; rash; arthralgia; pleural effusion). 8 pts discontinued NIL: 6 for AEs, 2 withdrew consent. No G4 AEs were reported. 32 pts had MMR (3-log reduction of Bcr-Abl; ≤0.1% IS) at entry; 16 additional pts achieved MMR on NIL. At entry, 18 pts had 4-log reduction and 10 pts 4.5-log reduction in Bcr-Abl. 16 and 13 additional pts achieved 4- and 4.5-log reduction, respectively, on NIL. At 3 mo (n=34) 62% and 53% pts reported QoL improvement from baseline in the previous 24 h and 7 d, respectively. Reduction in MDASI-CML severity/interference scores indicates symptom improvement. Mean reductions in MDASI-CML from baseline at 3 mo: severity, 1.21 (n=34); interference, 1.55 (n=33). Conclusions: 3 mo after switching to NIL, ~70% baseline chronic LG non-heme IM-related AEs improved and ≥53% of pts reported improvement in QoL. Molecular responses were maintained or improved in all patients. Switch from IM to NIL in majority of pts reduces IM-related toxicities and preserves/induces molecular response in CML-CP.
Correlation of TCR diversity with immune reconstitution after cord blood transplant.
Authors: Emerson Ryan , Milano Filippo , Guthrie Katherine , Sherwood Anna , Delaney Colleen , Robins Harlan 
Published: March 2020

6631 Background: Umbilical cord blood is an important source of hematopoietic stem cells for allogeneic transplants used to treat hematologic disorders and malignancies. Stem cells from cord blood has several advantages over other sources (peripheral blood or marrow) including reduced incidence of graft-versus-host disease (GvHD) which allows less strict donor-patient HLA-type matching requirements. However, hematopoietic recovery (both myeloid and platelet engraftment) and immune reconstitution is significantly delayed in CBT patients resulting in patients remaining at high risk of infection for an extended period of time. Though the high risk of infections to patients is well-documented and recognized, physicians lack an objective means to monitor each patient’s progress toward functional reconstitution of the adaptive immune system. Our project aims to test if our measure of TCR diversity is a better proxy of immune reconstitution in CBT patients. Methods: To do this, we compare our proposed measure of immune reconstitution, TCRB CDR3 sequence diversity and richness over time, against the observed clinical course of severe infection in patients who have received CBT. Previously, peripheral blood mononuclear cells (PBMC) were collected and cyropreserved from 35 CBT recipients at six time points, pre-transplant, and 28, 56, 100, 180, and 365 days post-transplant. Concordantly, clinical outcomes for these patients were collected for up to four years post-transplant. We use a t-test to test if size of TCR repertoire differs between CBT patients with non-relapse related mortality and all other CBT patients. Results: Our TCR sequencing method was successful at measuring immune reconstitution, and TCR diversity is predictive of subsequent mortality from severe infection by 56 days post-transplant. Conclusions: TCR repertoire sequencing is a viable method to monitor immune reconstitution.