bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allogenic stem cell transplant (ASCT) as initial salvage for patients (pts) with acute myeloid leukemia (AML) refractory to high-dose cytarabine-based induction chemotherapy.
Authors: Daver Naval Guastad , De Lima Marcos J.G. , Kantarjian Hagop , Ravandi Farhad , Bilen Mehmet Asim , Pierce Sherry , Khouri Issa F. , Dorkhom Stephan Joseph , Giralt Sergio , Garcia-Manero Guillermo , Nazha Aziz , Mathisen Michael , Pemmaraju Naveen , Cortes Jorge E. , Faderl Stefan , Jabbour Elias 
Published: March 2020

6544 Background: Outcomes of pts with AML who are refractory to High-dose Cytarabine (HiDAC) based induction are dismal. ASCT as initial salvage may be effective and potentially superior to repeat induction with combination chemotherapies in such pts. Methods: 1597 AML pts were treated with HiDAC-based induction at MD Anderson Cancer Center between 1995 and 2009. 285 primary refractory pts were identified. 28 (10%) of these underwent ASCT as initial salvage and were reviewed. Results: Median age was 56 years (36 to 77) and 50% were males. Median ECOG PS was 1 (0-2). Antecedent hematological disorders were present in 14 pts (50%). Median white cell count, hemoglobin, platelet count and bone marrow (BM) blast percentage at diagnosis were 3.5 x 109/l (0.6 to 73.6), 7.8 g/l (6.5 to 11.4), 44 x 109/l (9 to 615), and 43% (6-82), respectively. 9 pts (32%) had complex cytogenetics. FLT3 mutations were identified in 2 (15%) of 13 evaluated pts. All pts were refractory to HiDAC-based induction. HiDAC was combined with an anthracycline in 16 pts (57%) and non-anthracycline in 12 pts (43%). Median time from induction to ASCT was 76 days (28 to 184). Median BM blast and peripheral blast at ASCT were 28% (3 to 82) and 4% (0 to 41). 21 pts (75%) had matched related donors (18 sibling and 3 haploidentical) and 7 (25%) had matched unrelated donors. Conditioning regimens were melphalan-based, busulfan-based, fludarabine-based or others in 7 (25%), 10 (36%), 8 (29%) and 3 pts (10%); respectively. Complete remission (CR) was achieved in 23 of 28 pts undergoing ASCT (CR = 82%) with median time to CR of 31 days (26 to 134). 12 pts relapsed with median time to relapse of 5 months (2 to 19). 8 pts remain alive with median follow up of 80 months (28 to 118). Median overall survival (OS) for the entire group is 20 months (5 to 118). In historical series of pts with AML refractory to HiDAC-based induction, salvage chemotherapies induced CR rates of 22% with median OS of 4 months. Conclusions: Initial salvage with allogenic SCT is feasible and yields superior outcomes to salvage chemotherapy in primary HiDAC refractory AML pts. Randomized studies are warranted to further explore this treatment option.
Neurotoxicity after high-dose melphalan.
Authors: Najera Jose Eugenio , Sudhakar Tummala , Bashir Qaiser , Shah Nina , Champlin Richard E. , Qazilbash Muzaffar H. , Giralt Sergio , Hosing Chitra , Popat Uday R. , Ciurea Stefan O. 
Published: March 2020

6546 Background: High dose melphalan (HDM) at 200 mg/m2 is the standard preparative regimen for patients with multiple myeloma (MM) and light-chain amyloidosis (AL) undergoing autologous hematopoietic stem cell transplantation (auto-HCT). Neurotoxicity has been seen with HDM. In this report we describe the incidence, clinical manifestations and outcome of HDM- associated neurotoxicity. Methods: We performed a chart review of all patients who received HDM and auto-HCT for MM or AL between January 2007 to December 2009 at the University of Texas MD Anderson Cancer Center (MDACC). HDM- associated encephalopathy was defined as altered mental status, seizure or unexplained loss of consciousness within 30 days of auto-HCT. Patients with documented hemorrhagic or embolic stroke, or metabolic abnormalities were excluded. Results: 451 patients were included. Median age at auto-HCT was 59 years (range: 35-80). Thirty patients (6.6%) had AL and 61 patients (13.5%) had a pre-transplant serum creatinine of > 1.5 mg/dl. Nine patients (2.0%) developed HDM-associated encephalopathy with a median of 13 days (range 4-22) from auto-HCT. Among patients with encephalopathy, 8 (89%) developed changes in mental status ranging from drowsiness and confusion to loss of consciousness, while one patient had tonic-clonic seizures (11%). Of the affected patients there were 6 (66%) females, 8 patients (89%) > 59 years of age and only 2 patients (22%) had a creatinine clearance of < 60 ml/min. One patient was dialysis-dependent. A CT scan or MRI was obtained in all 9 patients. Only one patient had imaging abnormalities reported as posterior reversible encephalopathy syndrome (PRES). Electroencephalogram (EEG) was performed on 6 patients. Epileptiform activity was seen in one patient with clinical seizures. Mild generalized slowing was noted in 2 other patients with mental status changes. Cerebrospinal fluid was obtained in 2 patients and did not show any abnormalities. Complete resolution of neurologic symptoms was seen in all patients prior to hospital discharge, and there were no deaths. Conclusions: HDM-induced encephalopathy was seen in only 2% patients, and it is associated with complete neurologic recovery without any increase in transplant-related mortality.
Dose-intensive cyclophosphamide, etoposide, cisplatin reinduction for relapsed/refractory aggressive non-Hodgkin lymphoma (r/r-aNHL).
Authors: Henning Jan-Willem , Duan Qiuli , Bahlis Nizar J. , Daly Andrew , Duggan Peter , Shafey Mona , Stewart Douglas Allan 
Published: March 2020

6548 Background: Approximately 2/3 r/r-aNHL patients (pts) respond to salvage R-ICE or R-DHAP, 1/2 proceed to autologous stem cell transplantation (ASCT), and 1/3 achieve 3 year (yr) progression-free survival (PFS); however, PFS is only 20% if prior Rituximab, time to progression (TTP)<1yr, or age-adjusted International Prognostic Index (aaIPI)=2-3 [JCO 2010;28: 4184-90]. Since 1995, we re-induced poor prognosis r/r-aNHL with dose-intensive Cyclophosphamide 5.25g/m2, Etoposide 1.05g/m2 and Cisplatin 105mg/m2 (DICEP), G-CSF days (d) 14-19, and apheresis d19,20, or 21. Rituximab was added d0,7 after 2006. Methods: We retrospectively analyzed 113 consecutive transplant eligible r/r-aNHL pts [diffuse large B-cell=95, transformed=9, peripheral T-cell=6, other=3] who received one cycle of DICEP (n=93) or R-DICEP (n=20) from 1995-2009. Patient characteristics included: median age=49yr (22-69); primary refractory=68; TTP<1yr=85; elevated LDH=60; ECOG 2-4=42; aaIPI 2-3=59; bulk>10cm=26. Results: Of 113 pts, 77% responded to DICEP and 90% (102) proceeded to ASCT. The median CD34+ cells collected was 19x106/kg (0.3-142). Early treatment-related mortality (TRM) occurred in 3 pts (2.7%), and 4 others developed late second cancers (MDS/AML=2). With 94 months median follow-up (26-194), 5 and 10yr OS rates for all 113pts are 48% and 41%, and PFS rates are 42% and 37%, respectively. 5 year PFS rates for ASCT vs no-ASCT are 46% vs 9%, for relapse aaIPI=0-1 vs aaIPI=2-3 are 53.3% vs 32.1% (p=0.01), and for TTP>1yr vs <1yr are 63.9% vs 35.2% (p=0.009). Other predictors of inferior PFS in univariate analysis were elevated LDH, ECOG 2-4, no response to DICEP; however, PFS for 27 pts who failed prior Rituximab-chemotherapy (56%) was similar to other 86 pts (38%) (logrank p=0.09). Predictors of PFS and OS in multivariate analysis include: TTP<1yr, elevated LDH, bulk, no response to DICEP. Conclusions: (R)DICEP is an effective re-induction regimen for r/r-aNHL, leading to excellent stem cell mobilization and a high chance of proceeding to ASCT. Long-term PFS and OS rates compare favourably to reports of other re-induction regimens, and a prospective multicentre trial is warranted.
The comparison of up-front autologous peripheral stem cell transplantation in first remission and long-lasting intensive chemotherapy protocols in highly aggressive non-Hodgkin’s lymphomas: Results of a retrospective analysis.
Authors: Ozturk Mustafa , Ozaydin Sukru , Oyan Basak , Ozbalak Murat , Arpaci Fikret , Paydas Semra , Ataergin Selmin , Ferhanoglu Burhan , Kocak Necmettin , Gurkan Emel , Ozet Ahmet , Barista Ibrahim 
Published: March 2020

6550 Background: Optimal therapy in adult patients with Burkitt’s and lymphoblastic lymphoma are still unknown. Despite long–lasting and intensive chemotherapy protocols, post-transplant relapse is common and the chemotherapy period is time consuming. Methods: In this retrospective study, the results of induction and consolidation chemotherapies followed-by high dose therapy (HDT) and autologous peripheral stem cell transplantation (APSCT) (n=21), which was given in a time period of 3 months were compared to long–lasting and intensive chemotherapy protocols (LICP) (n=39) in patients with Burkitt’s and Lymphoblastic lymphoma, without bone marrow or central nervous system involvement at presentation. Cyclophosphamide, vincristine, prednisolone, doxorubicin (Adriamycin) with or without L–asparaginase were given as induction chemotherapy, followed-by a consolidation chemotherapy with DHAP and up-front HDT. Results: More than 60% of patients in both groups were in the intermediate and high risk group according to International Prognostic Index. There was no significantly difference according to age, gender, bulky disease, stage, Burkitt’s and Lymphoblastic lymphoma ratio in both groups (p>0,05). Median follow up was 32,3 months (min-max: 0-229 months). When HDT and LICP groups were compared: CR achieved in 76,3% and 82,1% of patients (p>0,05); Median PFS was 10,4 months (min-max: 6,1-20,3) and 10,1 months (min-max: 6,3- 69,0) (p>0,05); One year overall survival rate was 64,7% and 74,4% and five year overall survival rate was 50,1% and 56,7% (p>0,05) respectively. Conclusions: The current study suggests that induction and consolidation chemotherapies followed by HDT and APSCT have similar CR, PFS and OS rates when compared to more time consuming LICP therapies. This provides a short period of treatment with a high rate of survival in adult patients with highly aggressive lymphomas in first remission.
Validation of the M. D. Anderson Symptom Inventory multiple myeloma module.
Authors: Shah Nina , Jones Desiree , Mendoza Tito R. , Williams Loretta A. , Wang Xin Shelley , Vichaya Elisabeth G. , Sailors Mary H , Champlin Richard E. , Cleeland Charles S. 
Published: March 2020

6551 Background: Validated scales exist for quality of life assessment in patients with multiple myeloma (MM); however, no existing tool comprehensively assesses disease- and treatment-related symptoms in these patients. The aim of this study was to validate a module of the M. D. Anderson Symptom Inventory developed for patients with MM (MDASI-MM). The MDASI-MM includes 13 core symptoms, 6 interference items, and 7 MM-specific items: constipation, muscle weakness, diarrhea, sore mouth/throat, rash, difficulty concentrating, and bone aches. Methods: The MDASI-MM was administered to 2 cohorts of patients with MM. The first cohort (N=86) consisted of cross-sectional symptom data from patients at the beginning of induction chemotherapy or autologous hematopoietic stem cell transplant (HSCT). This cohort was used to demonstrate i) known-group validity, by detecting differences in groups by performance status; ii) concurrent validity, by correlating selected items and subscales from the MDASI-MM with those from the Short Form Health Survey (SF-12) and the EORTC-QLQC30; and iii) reliability, by computing Cronbach alpha values. The second cohort (N=53) consisted of symptom data collected at 2 points: prior to transplant and 7 days post-HSCT. This cohort was used to demonstrate the sensitivity of the MDASI-MM to detect acute worsening of patients’ symptoms post-HSCT. Results: The MDASI-MM detected significant differences in symptoms and interference levels according to patients’ performance status (P < .001). MDASI-MM scores correlated with those from SF-12 subscales for physical, emotional, cognitive, and social functioning (all P <.001) and with comparable items from the EORTC-QLQC30 (such as pain, fatigue, difficulty concentrating, constipation, and diarrhea, all P < .001). Cronbach alphas were 0.85 for symptom severity and 0.87 for interference. The MDASI-MM’s overall mean scores worsened between pre- and post-HSCT (1.32 vs. 2.55 (range = 0-10), P < .001). Conclusions: The MDASI-MM is a valid, reliable, and concise tool that can be used to quantitatively assess symptom severity and interference in clinical trials and care of MM patients.
Maintenance therapy with arsenic after induction in an alternative and long-term case for the prevention of recurrence of acute promyelocytic leukemia during the period between November 2005 and December 2011.
Authors: Aznab Mozaffar , Salimi Ghobad , Navabi Jafar , Jouybari Touraj , Rezaei Mansour , Ataee Mari , Kavianimoghadam Kaveh , Totoonchian Farhoud , Alimoghaddam Kamran 
Published: March 2020

6556 Background: Arsenic trioxide has been used in the first line treatment of acute promyelocytic leukemia and also for recurrence after ATRA and chemotherapy. In this study, it we used it in induction of remission and maintenance therapy Methods: Between November 2005 to December 2011, 42 patients admitted in our department with APL diagnosis. There were 27 male and 15 women with a median age of 28 years. Arsenic trioxide started at 0.15 mg/kg intravenous infusion till patient’s bone marrows achieve to complete remission. Then, after 28 days rest, we did consolidation with Arsenic trioxide with the same dosage for 28 more days. We continued treatment with 14 days courses of Arsenic trioxide every 3-4 months for 2 years, as maintenance therapy Results: Four patients died during the first 20 days of treatment. Thirty-eight patients achieved to remission. Two patients refused to continue treatment after achieving to remission and excluded from this study. Thirty-six patients finished whole treatment. After a median follow-up of 54 months, 4 patients died due to disease relapse and one patient relapsed and initiated treatment with Arsenic and ATRA. Five patients faced leukocytosis over 100,000/ml. In these cases we were obligated to discontinue Arsenic for 3-4 days and did chemotherapy by Danourobicin for 2 days. Totally 8 patients died during remission induction and long-term follow up. One year, 3 and 5 years RFS were 97%, 87.1% and 79.4 respectively and we didn’t observe any relapse for patients who remained in remission after 5 years. Finally, 31 patients are alive and free of disease. The overall survival was 79.5% for our cohort. Conclusions: Arsenic trioxide is an effective treatment as the first line therapy for new cases of APL and long term therapy with will reduce the risk of diseases recurrence without any major toxicity in long time.
Bendamustine retreatment of CLL in the outpatient setting.
Authors: Guenther Georg , Wilhelm Stefan , Tessen Hans Werner , Goettel Rainer , Sauer Annette ,   Project Team of Internal Oncology (p.i.o.)
Published: March 2020

6566 Background: Several studies have proven that bendamustine is a highly active drug in the therapy of CLL (Knauf et al. J Clin Oncol. 2009;27:4378-84; Fischer et al. J Clin Oncol. 2011;29:3559-3556). Nevertheless, only few data exist about the real-life use and efficacy of bendamustine-therapies in the non-trial setting. The project group of internal oncology (p.i.o.) therefore implemented a registry for patients in the routine use of bendamustine in the therapy of CLL (Sauer et al. Onkologie 2010;33(suppl 6):12). Since 2008 a total of 616 patients have been registered, out of which 473 have been thoroughly documented. To evaluate whether a retreatment with bendamustine in relapsed CLL is still active and well tolerable we present comparative data on therapies in patients with (group A) or without (group B) bendamustine pretreatment. Methods: 228 documented patients in relapsed situation were retrospectively appointed to one of two groups (see table below). Results: In Group A the ORR was 80 % and the median PFS lasted 15.6 month. In the patients without prior bendamustine treatment the ORR was 84% and the median PFS lasted 21.2 month. In both groups the median OS has not been reached yet. The grade 3/4 toxicities were mostly hematologic and comparable in both groups. Similar grade 3/4 toxicities were observed for neutropenia (about 25% of the patients), thrombocytopenia (16%) and infections (5%). Conclusions: Bendamustine is broadly used in the routine treatment of CLL. Bendamustine-therapies show impressionable high activity and tolerability, even in an advanced-line context with prior exposition to bendamustine. The treatment results are comparable to results of clinical trials and underline the quality and feasibility of bendamustine in the outpatient treatment. Nevertheless, it is to note that this is a registry and that both groups therefore are not composed of randomized patient-populations (cf. ECOG, patients in lines and ratio of rituximab combinations). [Table: see text]
AML patients with IDH1 or IDH2 mutations treated with hypomethylating agents: A case series.
Authors: Benton Christopher Brent , Ravandi Farhad , Andreeff Michael , Kantarjian Hagop , Konopleva Marina 
Published: March 2020

6576 Background: Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations play a significant role in acute myeloid leukemia (AML), yet optimal treatment for AML patients with IDH mutations remains unclear. IDH mutations have been associated with a globally hypermethylated genomic state, as the result of increased levels of 2-HG, a regulator of histone methylation. We sought to retrospectively determine responses of patients with IDH-mutated AML to treatment with hypomethylating agents. Methods: We reviewed clinical data for AML patients treated at The University of Texas M. D. Anderson Cancer Center from June 2001 to December 2011 whose stored leukemia samples from bone marrow aspirateshad been tested retrospectively for IDH1 and IDH2 mutations. We searched three databases that contained records for 407 AML patients. We selected patients who had been treated with the hypomethylating agents 5-azacitidine or decitabine, alone or in conjunction with other therapeutics. We retrospectively reviewed the patients’ medical records to obtain demographic, laboratory, treatment, and clinical data. We evaluated response measured by remission status, reduction in bone marrow blasts and peripheral blood blasts, and time to relapse. Results: We identified 104 patients (25.6%) who had either an IDH1 or IDH2 mutation, and of these, 8 patients had also been treated with hypomethylating agents. A ninth AML patient, who is IDH2-mutant, is currently undergoing treatment with decitabine alone. Of these 9 patients, three had a durable complete remission without recovery of blood counts (CRp), three had a partial response (PR), with or without blood count recovery, and three had no response. All 9 patients did have an initial decrease in the percentage of bone marrow blasts, peripheral blood blasts, or both. Conclusions: This series of patients demonstrates the possibility that AML patients with IDH1 or IDH2 mutations benefit from the use of hypomethylating agents, and suggests it is worthwhile to prospectively investigate treatment of patients with IDH-mutated AML using hypomethylating agents.
Real-world response monitoring and tolerability of imatinib-treated chronic myeloid leukemia patients captured in a retrospective research registry.
Authors: Stenehjem David D. , Albright Frederick S. , Guo Min Amy , Chen Lei , Raimundo Karina , Bauer Hillevi , Brixner Diana I. 
Published: March 2020

6583 Background: Monitoring tolerability and response to imatinib (IM) is an important aspect of chronic myeloid leukemia (CML) management. The objective of this study is to assess real-world tolerability and response monitoring in IM treated CML patients (pts). Methods: A comprehensive retrospective outcomes research registry of CML pts was created from the University of Utah electronic health record system. Study inclusion was limited to pts diagnosed with CML in chronic phase in 2001 to 2010 and treated with IM as a first-line therapy. Utilization and outcome of cytogenetic and molecular testing within 18 months of IM initiation, rates of adverse drug events (ADEs), and therapy modifications were evaluated by chart review. Results: A total of 92 pts were treated with IM as first-line therapy. Within the first 18 months of treatment, cytogenetic testing was recorded in 45 pts (49%) and of these 33 pts (73%) achieved a complete cytogenetic response (CCyR) in a median of 241 days (range: 110-542); molecular testing was completed in 48 pts (52%) and of these 24 pts (50%) achieved at least a major molecular response (MMR) in a median of 254 days (range: 99-546). Imatinib associated ADEs of any grade (n = 60) occurred in 42 (46%) pts resulting in dose reductions in 15 pts (36%) in a median of 77 days and discontinuation of IM occurred in 9 (21%) pts in a median of 130 days. The IM dose was increased to >400 mg in 21 (23%) pts in a median of 457 days (range: 21-2112). Of pts diagnosed between 2006 to 2010 (n = 34; 37%), 8 (25%) pts transitioned to dasatinib or nilotinib in a median of 397 days (range: 147 to 1057). Reasons for therapy change included physician documented suboptimal response or treatment failure (n = 5) and ADEs to IM (n = 3). Conclusions: Utilization of cytogenetic and molecular testing within 18 months of IM initiation was lower than the National Comprehensive Cancer Network or European LeukemiaNet CML guidelines would suggest. Further research is warranted to understand limited response monitoring and outcomes in non-monitored pts. The ADE rate was similar to clinical trial data. The impact of ADEs on subsequent treatment and outcomes in CML pts deserves further study.
Ofatumumab retreatment and maintenance in patients with fludarabine-refractory CLL.
Authors: Österborg Anders , Dyer Martin J. S. , Mayer Jiri , Hess Georg , Hillmen Peter , Schetelig Johannes , Schuh Anna , Smolej Lukas , Beck Christian , Dreyfus Brigitte , Hellman Andrzej , Kozlowski Piotr , Pfreundschuh Michael , Rizzi Rita , Spacek Martin , Chan Geoffrey , Gupta Ira , Phillips Jennifer , Lisby Steen , Wierda William G. 
Published: March 2020

6584 Background: In Study 406, the anti-CD20 monoclonal antibody ofatumumab (ofa), given as monotherapy over 6 months, showed 47% overall response rate (ORR) in patients (pts) with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab (FA-ref), or to fludarabine with bulky (>5cm) lymphadenopathy (BF-ref). The effects of ofa retreatment (retx) and maintenance (mt) are unknown. Methods: Pts who responded to ofa and then progressed or had stable disease (SD) in Study 406, were offered retx in Study 416 (NCT00802737; GSK/Genmab) with ofa 1 x 300 mg + 7 x 2000 mg weekly followed by mt with ofa 2000 mg monthly for up to 2 years (if SD or better). Primary endpoint was ORR (1996 NCI-WG). Safety and time to event outcomes were also assessed. Results: Of 29 pts enrolled, 7 had SD and 22 had partial response (PR) and progressed in Study 406. Pts were defined per Study 406: 17 FA-ref, 11 BF-ref, 1 “other”. Pretreatment characteristics were similar between groups. Pts received a median of 12 doses (range 3-32); 86% had 8 doses, 3% received all 32 doses. 72% of pts had infusion-related adverse events (AEs), 41% at 1st infusion, mostly grade 1-2. The most common grade >3 AE occurring up to 60 days after last tx was infection (38%); the most common was pneumonia (17%). 3 pts (10%) had fatal infections, all bronchopneumonia. Clinical efficacy is shown in Table. Comparative analysis to Study 406 is ongoing. Conclusions: The response to ofatumumab (ofa) as induction retreatment and progression-free survival in this limited number of pts was similar to 1st treatment (Study 406). Ofa maintenance had some clinical benefit for pts with advanced CLL. Ofa was well-tolerated with no unexpected toxicities. [Table: see text]