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PURPOSE Standard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy. PATIENTS AND METHODS One hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital. RESULTS Mean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed. CONCLUSION Subjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.

In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (

Background: Disparities driven by socioeconomic factors have been shown to impact outcomes for cancer patients. We sought to explore this relationship among patients with multiple myeloma (MM) who were not considered for hematopoietic stem cell transplant in the first-line setting and how it varied over time. Methods: We queried the National Cancer Database for patients diagnosed with MM between 2004 and 2016 and included only those who received systemic therapy as the first-line treatment. Enrollment rates for therapy were calculated as receipt of systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator) and used to calculate incident rate ratios that were further analyzed using Poisson regression analysis. A multivariate Cox proportional hazards model was constructed for survival analysis, and differences were reported as hazard ratios (HRs). Results: We identified 56,102 patients for enrollment analysis and 50,543 patients for survival analysis. Therapy enrollment in a multivariate model was significantly impacted by race and sex (p 1), whereas female sex, non-Hispanic black race, higher income, and treatment at an academic center were associated with improved survival (HR

Mantle cell lymphoma is an aggressive and incurable subtype of non‐Hodgkin B cell lymphoma. Patients typically present with advanced disease, and most patients succumb within a decade of diagnosis. There is a clear and urgent need for novel therapeutic approaches that will affect mantle cell lymphoma through a unique mechanism compared to current therapies. This study examined the use of RNA interference (RNAi) therapy to attack mantle cell lymphoma at the mRNA level, silencing genes associated with cancer cell proliferation. We identified a lipid nanoparticle formulated with the lipidoid 306O13 that delivered siRNA to JeKo‐1 and MAVER‐1 mantle cell lymphoma cell lines. Three therapeutic gene targets were examined for their effect on lymphoma growth. These included Cyclin D1, which is a cell cycle regulator, as well as Bcl‐2 and Mcl‐1, which prevent apoptosis. Gene knockdown with siRNA doses as low at 10 nM increased lymphoma cell apoptosis without carrier‐mediated toxicity. Silencing of Cyclin D1 induced apoptosis despite a twofold “compensation” upregulation of Cyclin D2. Upon simultaneous silencing of all three genes, nearly 75% of JeKo‐1 cells were apoptosing 3 days post‐transfection. Furthermore, cells proliferated at only 15% of their pretreatment rate. These data suggest that lipid nanoparticles‐formulated, multiplexed siRNA “cocktails” may serve as a beneficial addition to the treatment regimens for mantle cell lymphoma and other aggressive cancers.

Introduction Determining eligibility for autologous hematopoietic stem cell transplantation (Auto-HCT) is considered standard of care for patients with newly diagnosed multiple myeloma (MM). In addition to comorbidity score, age >65 years is still a commonly used criterion to deem patients ineligible for transplant. Here we report the outcomes of patients ³ 65 years with MM who underwent Auto-HCT following risk stratification using HCT-CI along with other eligibility criteria. Methods We performed a retrospective analysis of 102 patients, who underwent Auto-HCT between 1/1/1999 and 12/31/2018 at Allegheny Health Network Cancer Institute. Ninety two patients (90%) received conditioning with Melphalan 200 mg/m2. Median overall survival (OS) was estimated at day+100, day+180, 1, 2, 3 and 5 years post Auto-HCT. Non-relapse mortality (NRM) was assessed at day 100 post Auto-HCT. Results For a cohort of 102 patients, a total of 119 Auto-HCT were performed. Median age at transplantation for the entire cohort was 69.2 years (65.1 - 79.4 years). Thirty five (34.3%) patients were aged ³70 years. Median HCT-CI score was 3 (range: 0-8). Median time to Auto-HCT following diagnosis was 9.1 months (range: 4.7- 176.7 months). Median time to ANC500 and PLT20 was 13 days (range: 10-15) and 18.4 days (range:8-42) respectively. Median OS by Kaplan-Meier analysis for the entire cohort vs patients ³ 70 years at day+100, day+180, 1, 2, 3, and 5 years post Auto-HCT was 97.1%, 95.1%, 91.2%, 83.3%, 78.4%, and 63.7% respectively vs 100%, 100%, 97.1%, 82.9%, 77.1% and 68.6% respectively. Median OS in months for patients Conclusion Auto-HCT in patients with MM aged ³65 years is safe, effective and should be offered to all patients with a reasonably good performance status. A fully integrated approach is required to accomplish the needs of elderly patients including consideration for quality of life.

Hospitalized patients with hematological malignancy (HM) suffer an increased incidence of venous thromboembolism (VTE). We sought to identify risk factors and rate of VTE in hospitalized patients with HM using National Inpatient Sample (NIS) for the years 2011 to 2015. We used ICD-9 codes to identify patients with HM as the primary diagnosis and VTE as a secondary diagnosis for hospitalization. The rate of VTE was highest in patients with acute myeloid leukemia (6.6%) followed by acute lymphocytic leukemia (6.1%) and non-Hodgkin's lymphoma (6.0%). The highest risk of VTE occurred among patients with HM receiving chemotherapy (OR 1.68; 95% CI 1.567-1.809) followed by infection such as pneumonia (OR 1.31; 95% CI 1.201-1.436) and sepsis (OR = 1.66; 95% CI = 1.524-1.621). Chemotherapy had the highest risk of developing VTE during hospitalization followed by sepsis and pneumonia. The identification of patients with HM most at risk for VTE could be used to design and test prophylactic strategy.

Background The treatment options in Multiple Myeloma (MM) are variable and may involve combinations of chemotherapy, immunomodulatory therapy, monoclonal antibodies and stem cell transplant. In the present study, we hypothesized that socioeconomic factors impact the treatment and survival of patients with MM who receive systemic therapy as firstline treatment. Methods We queried the National Cancer Database (NCDB) for patients with MM (ICD-0-3 code 9732) diagnosed from 2004-2016. We included only that received systemic therapy as first line treatment. Active MM patients were defined as those treated within 120 days of diagnosis. Enrollment rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy or TTI (denominator) and used to calculate incident-rate ratios that was further analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, 1, p-value Citation Format: Thejus Jayakrishnan, Veli Bakalov, Zena Chahine, John Lister, Rodney Wegner, Santhosh Sadashiv. Disparities in the enrollment to systemic therapy and survival for patients with multiple myeloma [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-212.

Our group has demonstrated that combinations of epigenetic modifiers produce potent synergy in pre-clinical models of PTCL, and has confirmed this data in early phase clinical studies. We showed that the combination of romidepsin and hypomethylating agents, decitabine or azacytidine, uniquely induces the expression of genes, including cancer testis antigens, gamma interferon and endogenous retrovirus. We are conducting a phase 1 study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma. In addition, we are conducting a Phase 1/2A study of durvalumab combined with oral 5-azacitidine + romidepsin (Arm A), pralatrexate + romidepsin (Arm B), romidepsin (Arm C), or oral 5-azacitidine (Arm D) in patients with PTCL. Patient characteristics are listed in Table 1. We have treated a total of 12 patients across the 2 trials and 4 different Arms including pralatrexate plus pembrolizumab (3 patients), pralatrexate, decitabine and pembrolizumab (3 patients), decitabine and pembrolizumab (3 patients) and azacytidine, romidepsin and durvalumab (3 patients). Twelve patients out of 12 received at least one dose of drug and were evaluable for toxicity. There was a dose limiting toxicity (DLT) for each arm including prolonged grade 3 thrombocytopenia, febrile neutropenia, grade 3 hyponatremia and rash, and cytokine release syndrome, respectively. There were no treatment-related deaths. Eight patients out of 12 are evaluable for response at the time of this analysis. Three out of 8 patients achieved a complete remission, 3 out of 8 patients had a partial remission, and 2 out of 8 patients experienced progression of disease. Interestingly, all of the responses were seen in the triple combination of pralatrexate, decitabine, pembrolizumab and azacytidine, romidepsin and durvalumab. These preliminary clinical data suggest that the addition of immune-checkpoint inhibitors on an epigenetic backbone is safe and demonstrates encouraging responses in patient with PTCL and CTCL. These trials are registered at www.clinicaltrials.gov (NCT03240211, NCT03161223). Patient characteristics (n=12)Median age (range)68 (26-77)Sex, n (%) Male Female6 (50) 6 (50)Race, n (%)White/Non-Hispanic White/Hispanic Black Asian Unknown5 (42) 1 (8) 3 (25) 1 (8) 2 (17)Histology, n (%) PTCL, NOS AITL Mycosis Fungoides PTCL, NOS TFH ATLL Sezary Syndrome ALCL, ALK+2 (17) 2 (17) 2 (17) 1 (8) 1 (8) 1 (8) 1 (8)Stage at diagnosis IB II III IV Unknown1 (8) 2 (17) 3 (25) 4 (33) 2 (17)Median number of prior therapies (range) **2 unknown3 (0-5) Citation Format: Enrica Marchi, Helen Ma, Francesca Montanari, Ahmed Sawas, Jennifer K. Lue, Changchun Deng, Kareema T. Whitfield, Sandra Klein, Matthew V. Matthew, Freedy J. Loffredo, Luigi Scotto, Hyejung Lee, Hye A. Kim, Alice T. Jacobs, Aishling M. Rada, Karen A. Khan, Salvia Salvia, John Lister, Nora N. Benanni, Mark A. Francescone, Pier Luigi Zinzani, Wonseog Kim, Owen A. O'Connor. The integration of PD1 blockade with epigenetic therapy is highly active and safe in heavily treated patients with T-cell lymphoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT160.

8049 Background: Our group has demonstrated that combinations of epigenetic modifiers produce potent synergy in pre-clinical models of PTCL and induce the expression of cancer testis antigen, suggesting a role in the addition of the immune-checkpoint inhibitor, pembrolizumab. Methods: This is a phase 1b study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with relapsed and refractory PTCL and CTCL. A standard 3+3 dose-escalation is applied in the triplet Arm (Arm B) while in the doublet Arms (A and C) de-escalation is applied in case of toxicity. Pharmacokinetic and pharmacodynamic studies are ongoing. Results: We treated a total of 12 patients with 4 patients in each Arm. All patients that received at least one dose of drug were evaluable for toxicity. There was a dose limiting toxicity (DLT) in each arm including prolonged grade 3 thrombocytopenia (Arm A), febrile neutropenia (Arm B), grade 3 hyponatremia, and rash (Arm C). There were no treatment-related deaths. Six patients out of 12 were evaluable for response at the time of this analysis. One patient achieved a complete remission, 2 had partial remission, 1 had stable disease, and 2 experienced progression of disease. Interestingly, all of the responses were seen in the triple combination of pralatrexate, decitabine, and pembrolizumab. Table summarizes the patient characteristics, toxicities, and response rates. Conclusions: These preliminary clinical data suggest that the integration of pembrolizumab on an epigenetic backbone is safe and demonstrates encouraging responses in patient with PTCL and CTCL. Clinical trial information: 03240211 . [Table: see text]

Treatment of diffuse large B cell lymphoma (DLBCL) remains challenging in elderly population and systematic reviews are lacking in this area. Medline and Cochrane Register of Controlled Trials in addition to conference proceedings were searched for therapeutic clinical trials on frontline treatment of DLBCL in adults ≥60 in post-rituximab era. Forty-one out of 713 reviewed papers met our inclusion criteria. Six cycles of rituximab, cyclophosphamide, vincristine, prednisone (R-CHOP) administered every 21 d remain the standard treatment for fit elderly, with no role for maintenance rituximab. For individuals ≥80, the strongest evidence favors rituximab/ofatumumab-miniCHOP. Numerous alternative approaches including the use of liposomal anthracyclines, dose and regimen adjustment to frailty/comorbidity score, brief duration regimens, and consolidative radioimmunotherapy have produced promising outcomes and could be considered for R-CHOP inappropriate elderly. Phase III randomized trials studying the efficacy of liposomal vincristine, extended-exposure rituximab, and lenalidomide plus R-CHOP are ongoing.

Introduction BK virus hemorrhagic cystitis is a well-recognized complication in patients undergoing allogeneic HSCT and is associated with significant morbidity. PTCY has been used for GVHD prophylaxis in patients undergoing haploidentical or mismatched unrelated donor HSCT. We hypothesized that PTCY is associated with increased incidence of HC associated with BK virus. Objectives • To identify the risk factors for developing BKHC in allogeneic HSCT • To assess the effect of PTCY in development of BKHC in patients with myeloablative (MA) regimen containing total body irradiation (TBI) • To evaluate the risk of concurrent CMV infection and BKHC in allogeneic HSCT with MA conditioning regimen Methods We identified 116 consecutive patients who underwent allogeneic HSCT at our institution between January 2015 and July 2018. The MA regimen (n=42) consisted of fludarabine 50 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 4 days with or without TBI of 200 cGy/day for 2 days (FBT or FB4). The reduced intensity conditioning (RIC) regimen (n=74) consisted of fludarabine 30 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 2 days (FB2). In terms of GVHD prophylaxis all recipients except those undergoing haploidentical and mismatched unrelated transplant received Thymoglobulin 2 mg/kg/daily IV days -2, -1 and 0 (n=80). Recipients of haplo- related and mismatched unrelated donor transplantation received cyclophosphamide 50 mg/kg IV on day +3 and +4 along with Mesna (n=36). All patients received post-transplant immunosuppression with Tacrolimus and Mycophenolate Mofetil. Patients with urinary symptoms were tested for BKV in urine by PCR. Results The median age of patients was 56 years (range 20–76). A total of 31% of patients (n=13) received PTCY in FBT group which was similar to 31% of patients (n=23) in FB4-FB2 (p=0.98). Overall 21.5% patients were diagnosed with BKHC. The patients who received ATG, the incidence of BKHC was 27.5% in FBT group and 11.7 % in FB4-FB2 (p=0.073). The patients who received PTCY, the incidence of BKHC was significantly increased to 69.2% in FBT vs 9% in FB4-FB2 (p=0.0001). The risk of developing concurrent CMV viremia and BKHC was increased to 10.3% in FBT compared to 5.8% in FB2-FB4 (p=0.662). The patients who received PTCY following FBT, the incidence of concurrent CMV viremia and BKHC was increased to 23.1%. as compared to 0% with FB2-FB4. Conclusion Our result shows the addition of PTCY to TBI containing regimen significantly increased the incidence of BKHC. We did not observe increase in the incidence of BKHC in patients receiving PTCY with FB2 or FB4 regimens. Our study revealed an increased incidence of concurrent BKHC and CMV viremia in patients receiving PTCY with FBT which could be due to increased immunosuppression. Our findings suggest that using PTCY as GVHD prophylaxis in patients undergoing MA conditioning regimen including TBI is a risk factor for BKHC.

Objective We compared the quality of care in admitted febrile neutropenic cancer patients presenting through the emergency department (ED) vs those directly admitted (DA) from the clinic or infusion center. We hypothesized that the quality of care would be comparable between these 2 pathways. Methods We conducted a retrospective, observational cohort study of all adult cancer patients hospitalized with subjective or objective fever (≥100.4°F) and documented neutropenia (absolute neutrophil count ≤1000/mm 3 ) from January 1, 2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including patient age, sex, race, tumor type, blood culture growth, temperature (actual or reported), pathway to admission (ED or DA), time to antibiotic administration, length of stay, and the Multinational Association for Supportive Care in Cancer (MASCC) risk score. The primary outcome measures were time to antibiotic administration, appropriateness of antibiotic(s) administered based on published guidelines, length of stay, and MASCC score–based risk assessment. We used the t test for the difference between 2 means with unequal population variances to compare these outcome measures between ED and DA patients. Results One hundred twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA visits). Mean time to antibiotic administration, mean length of stay, appropriateness of antibiotics, and MASCC score–based risk assessment were comparable between ED and DA visits ( P >.05 for all comparisons). Conclusion The quality of care for febrile neutropenia in patients presenting through the ED was comparable to those directly admitted to the hospital in this 2-center study.

Extramedullary relapse (EMR) of acute promyelocytic leukemia (APL) is a rare entity, with predilection to involve the central nervous system (CNS). Risk factors include leukocytosis of > 10 × 10 9 /L, bcr3 isoform, microgranular variant, age > 45 years and development of subarachnoid hemorrhage (SAH) during induction therapy. We report a case of APL who completed induction and consolidation therapy but subsequently relapsed with leptomeningeal involvement. Retrospectively, we identified several risk factors for EMR in our patient. Interestingly, the use of all-trans retinoic acid has recently been associated with higher risk of EMR possibly due to up-regulation of adhesion molecules on the surface of the leukemic cell, resulting in their passage through the endothelium to extramedullary tissues. However, data remain conflicting in that regard. Although universal CNS prophylaxis has been suggested, the low incidence of EMR among APL patients renders this strategy less attractive. Nonetheless, active surveillance and CNS prophylaxis may be considered in patients at high risk for EMR, particularly in those of SAH during induction therapy. Further research is needed to evaluate the effectiveness and safety of this strategy. World J Oncol. 2014;5(2):77-80 doi: http://dx.doi.o rg/10.14740/wjon761 w

Summary The multicentre, open-label, two-stage, single-arm, phase 2, PILLAR (PIvotaL Lymphoma triAls of RAD001)-1 study (NCT00702052) assessed the efficacy and safety of everolimus 10 mg/d in adults with confirmed mantle cell lymphoma (MCL) refractory to or intolerant of bortezomib who received ≥1 other antineoplastic agent, either separately or in combination with bortezomib. Primary endpoint was overall response rate (ORR) per investigator review according to the response criteria for malignant lymphoma. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Fifty-eight patients were enrolled from August 2008–January 2011. Five partial responses were observed (ORR 8·6%; 90% confidence interval [CI] 3·5–17·3%); the study did not meet the prespecified objective of ≥8 objective responses among 57 patients. Median PFS and OS were 4·4 months (95% CI 3·5–6·1) and 16·9 months (95% CI 14·4–29·9), respectively. Grade 3/4 non-haematological toxicities occurred in 70·7% of patients. Based on laboratory values, grade 3/4 thrombocytopenia, neutropenia and anaemia occurred in 13·8%, 13·8% and 8·6% of patients, respectively. Everolimus demonstrated modest activity and acceptable tolerability in heavily pretreated patients with MCL refractory to or intolerant of bortezomib. Future studies evaluating everolimus in a less refractory population or in combination with other targeted therapies in refractory MCL are warranted.

Background: ASTX660 is an oral, novel nonpeptidomimetic, small-molecule antagonist of cellular/X-linked inhibitors of apoptosis proteins (cIAP1/2 and XIAP). ASTX660 is currently being evaluated in a first-in-human phase 1–2 study in patients (pts) with advanced solid tumors or lymphoma (ClinicalTrials.gov NCT02503423). In the ongoing phase 2, ASTX660 has demonstrated preliminary evidence of clinical activity in the relapsed/refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) cohorts (Mehta et al, presented at the EHA Conference 2019, abs PS1073). Here, we report overall efficacy and safety data from the solid tumors (head and neck squamous cell carcinoma [HNSCC]; cervical carcinoma and other solid tumors) and lymphoma (diffuse large B-cell lymphoma [DLBCL], PTCL, CTCL,) phase 2 cohorts. Methods: Pts received treatment with ASTX660 orally at the RP2D 180mg/day on days 1 to 7, and 15 to 22 in a 28-day cycle. In the first stage 14 evaluable pts were enrolled in each of the 6 phase 2 cohorts with the option to expand the cohort if activity was observed. The primary endpoint was response rate as assessed by the investigator according to the Lugano criteria (DLBCL and PTCL), Global Assessment (CTCL), or RECIST 1.1 (solid tumors). Adverse events (AEs) were assessed per CTCAE V4.03. Results: As of June 4, 2019, a total of 107 pts have received ASTX660 in the solid tumors and lymphoma phase 2 cohorts (HNSCC n=14; DLBCL n=16; PTCL n=26; CTCL n=23; cervical carcinoma n=14; other solid tumors n= 14). Median age (range) was 61 (23-84) years and median number (range) of prior anticancer regimens was 3 (0-12). Among all pts, the most common related AEs of any grade (≥ 10%) were rash (35%), lipase elevation (34%), amylase elevation (29%), diarrhea (14%), fatigue (14%), AST elevation (13%), nausea (13%), and anemia (11%). Related AEs ≥ Grade 3 occurring in ≥ 5% of pts were rash (18%), lipase elevation (16%) and amylase elevation (9%). As of 4 June 2019, 86 pts (80%) discontinued study treatment: 64 (60%) due to progressive disease, 13 (12%) due to AE, 4 (4%) due to death, 4 (4%) due to withdrawal by participant and 1 (1%) for investigator’s decision. At the time of analysis, the ORR was 36% in the PTCL cohort and 15% in the CTCL cohort. One PR was reported in a pt with metastatic melanoma after 12 cycles of treatment. No objective responses were reported in the HNSCC, DLBCL or cervical cohorts. Accrual in the PTCL and CTCL continues; updated efficacy and safety data will be presented at the meeting. Conclusion: In the phase 2 part of the study ASTX660 monotherapy has demonstrated a manageable safety profile and encouraging activity in PTCL and CTCL warranting cohort expansion. Future plans include evaluation of ASXT660 both as mono- or combination therapy in selected malignancies. Citation Format: Antoine Hollebecque, Sarit Assouline, Felipe Samaniego, Benoit You, Francine Foss, Anca Prica, Sarah W. Gordon, Marc Webster, Martin JS. Dyer, Dima El-Sharkawi, Geoffrey I. Shapiro, Lisa Nabell, Sarah P. Blagden, John Lister, Susanna V. Ulahannan, Yijun Sun, Danna Chan, Roberta Ferraldeschi, Monica Mita. Preliminary results of ASTX660, a novel non-peptidomimetic cIAP1/2 and XIAP antagonist, in 107 patients with solid tumors or lymphoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A072. doi:10.1158/1535-7163.TARG-19-A072

Introduction. The diagnosis of multiple myeloma (MM) is often made in elderly individuals (median age at diagnosis 69 years) with over a third of patients exceeding 75 years of age. Many elderly patients are frequently excluded from clinical trials because of predefined upper age limit of 65 years limiting accessibility to autologous stem cell transplant (ASCT) for a large proportion of MM patients. Based on limited multicenter studies and randomized clinical trials in this population, we used the National Cancer Database (NCDB) to assess the outcomes of ASCT in MM patients older than 65 years of age. Methods. We queried the NCDB for patients with MM diagnosed between 2004 -2015 treated with ASCT as frontline therapy, yielding a final cohort of 9,383 patients. Multivariable logistic regression was used to determine the likelihood of receiving ASCT. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier methodology. Adjusted hazard ratios (HR) and 95% confidence interval (CI) are reported, with α=0.05 used to indicate statistical significance. Results. The median age was 67.0 (range: 19-90). The majority of patients were older than 65 (58.5%), male (54.7%), Caucasian (75.6%), had government insurance (88%)and had a Charlson-Deyo Comorbidity score (CDCS) of 0 (75.5%). In addition to older age, insurance status, low annual income higher CDCS were associated with lower chances of receiving ASCT (Table 1). Patients in Urban areas (OR 1.377, CI 95% 1.286-1.475), and patients in Academic/Research Centers (OR 4.379 were CI 95%, 3.852-4.978) were more likely to receive ASCT. In patients younger than 65-years of age rate of ASCT was 7.0% in 2004 and increased to 16.7% in 2015. The annual rate of ASCT in patients older than 65-years of age was 1.1% in 2004 and increased to 4.7% in 2015. The multivariable cox proportional hazards of death in patients receiving ASCT was associated with improved survival (HR 0.492, CI 95% 0.473-0.512). Age (>65 years old HR 1.184, 95% CI 1.053-1.331), insurance status (uninsured HR 1.361, CI 95% 1.302-1.422, Medicaid HR 1.365, 95% CI 1.318-1.414, Medicare HR 1.271, 95% CI 1.244-1.299) and higher comorbidity score were associated with worse survival (Table 2). Median survival in patients younger than 65-years old receiving ASCT was 102.6 month versus 66.6 months in patients not receiving ASCT (HR 0.596, 95% CI 0.568-0.624) (Figure 1). Median survival in patients older than 65 years old and not receiving ASCT was 86.3 months versus 28.4 months in patients not receiving ASCT (HR 0.344, 95% CI 0.0320-0.371). Conclusions. The findings of the present study demonstrate decreased utilization of ASCT in older patients with MM, despite significant survival benefit of such therapy. Other factors associated with decreased likelihood of ASCT are such as insurance status and annual income unfold existing disparities in patients with MM receiving ASCT. Disclosures No relevant conflicts of interest to declare.

Background. Use of Autologous Stem Cell Transplantation (ASCT) continues to increase in elderly patients with multiple myeloma. The main goal of our study was to describe in-hospital complications and outcomes after ASCT in patients younger and older than 65-years old utilizing the Nationwide Inpatient Sample (NIS) database. Methods. Cohort selection. The NIS database for the years 2011 to 2015 was queried for the analysis. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) in order to identify patients with MM as a primary diagnosis for the hospitalization, and ASCT as a primary diagnosis of the hospitalization. In order to determine comorbidities in selected population we used Clinical Classifications Software (CCS) in conjunction with ICD-9-CM codes. Statistical Analysis.Complex weights were used throughout all calculations, enabling appropriate national projections. Chi-squared and independent t-tests were used for univariate analysis where appropriate. In our study p-value Results.A total of 3,664 patients with MM receiving ASCT were identified in our cohort. Males represented 57.1% of the population, majority of the patients were white, with private insurance, located at the urban teaching hospitals (Table 1). Main insurance in patients older than 65 years old was Medicare. Main comorbidities during hospitalization were anemia, hypertension, electrolyte abnormalities, acute kidney injury, cardiac dysrhythmias, sepsis and pneumonia (Table 2). Overall in-hospital mortality was low, 0.7%, and was significantly higher in patients older than 65 years old (1.3% vs 0.4%, p-value 0.002), however when adjusted for the baseline characteristics with multivariate logistic regression analysis in-hospital mortality was no longer statistically significant (Table 3). Conclusions. We found that patients older than 65 years with MM receiving ASCT are more susceptible to in-hospital complications. However we found that in-hospital outcomes are not statistically significant when adjusted to baseline characteristics, suggesting that the procedure is safe even in the elderly population. Findings of our study can be used to design future randomized controlled trials. Disclosures No relevant conflicts of interest to declare.

11589 Background: Opioid medications are the mainstay for treating cancer pain. Goal of this study was to identify risk factors for opioid abuse/dependence in patients hospitalized with cancer, explore whether risk of opioid abuse/dependence varies by cancer type and to assess whether opioid abuse/dependence in cancer patients effects the outcomes of hospitalization. Methods: The Nationwide Inpatient Sample for the years of 2011-2015 was queried for the analysis. We used ICD-9-CM codes of solid tumors as a primary diagnosis for hospitalization, and opioid abuse/dependence as a secondary diagnosis of the hospitalization. We performed univariate and multivariate logistic regression analyses to examine the association between risk factors and opioid abuse/dependence. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC). Results: Total of 524,624 patients were included in our cohort. Rate of opioid abuse/dependence was highest in patients with liver cancer (1.77%). Opioid abuse/dependence was less associated with age (>65 years old: OR 0.29, 95% CI 0.21-0.39). Patients with Medicaid insurance associated with increased risk of opioid abuse/dependence comparing to other insurances (OR 5.29, 95% CI 4.78-5.86). Strongest association with opioid abuse/dependence were in patients with liver cancer (OR 6.07, 95% CI 5.11-7.20) followed by head and neck cancer (OR 3.20, 95% CI 2.67-3.84). Substance abuse (OR 9.9, 95% CI 9.04-10.84), mental disease (OR-2.87, 95% CI 2.64-3.13) and nutrition deficiency (OR-2.09, 95% CI 1.90-2.31) were highly associated with opioid abuse dependence. Inhospital mortality rate, total cost of hospitalization, and length of stay were significantly higher in patients with opioid abuse/dependence (Table). Conclusions: We identified risk factors for opioid abuse/dependence in hospitalized patients with cancer and demonstrated that risk of opioid abuse varies by cancer type, and opioid abuse/dependence affects the outcomes of hospitalization. Findings of our study can be used for development of the screening tools with higher sensitivity and specificity for predicting the risk of opioid abuse/dependence in cancer patients.[Table: see text]

Introduction and Objectives Multiple myeloma (MM) is a disease of the elderly with the median age of diagnosis being 66 years and rare in the population younger than 50 years. Younger patients generally undergo autologous HCT as part of their treatment once they achieve an adequate response. Overall survival in patients with MM has dramatically improved over the last 2 decades with the advent of novel agents. The purpose of this retrospective analysis was to evaluate the disease behavior and transplant outcomes in patients younger than 50 years. Methods We retrospectively reviewed the charts of 29 patients aged ≤50 who underwent autologous HCT between May 2003 and Dec 2017 at our institution. All patients received Melphalan as their conditioning regimen. 28% (n=8) of the patients had renal insufficiency at the time of diagnosis (serum Creatinine ≥ 2.0 mg/dl). Results 38 auto-HCTs were performed in this group of patients. 7 patients underwent salvage transplant and 2 patients underwent planned tandem auto-HCT. Nearly 80% (n=23) patients had Salmon Durie stage 3 disease at the time of auto-HCT. Overall survival for the entire cohort was 109 months and PFS was 51 months. Median age at diagnosis was 46 years. The median age of the first transplant is 47 years. Median time to relapse/progression was 31 months after auto-HCT for the entire cohort. For patients with high-risk cytogenetics (28%, n=8) median time to relapse was 13 months compared to 72 months in standard risk patients. There was total of 12 deaths in the entire cohort with the majority of deaths (10/12) due to disease progression/relapse and 1 died from a secondary malignancy. Median time to relapse/progression after salvage HCT was 16 months. Of the 7 patients who underwent salvage HCT, 3 died secondary to disease progression with a median time to death is 12.6 months. Conclusion Despite recent advances in the treatment of multiple myeloma, younger patients with high-risk disease status continue to have poor outcomes. Aggressive induction regimens and possible planned tandem Auto-PBSCT may be a reasonable approach to improve outcomes in younger patients with high-risk disease status. Further studies with a larger cohort are warranted to corroborate our findings and also find ways to improve survival in this high-risk group.

Mantle cell lymphoma (MCL) is a B-cell lymphoma that accounts for 3% to 10% of the non-Hodgkin forms of lymphoma. MCL almost universally expresses CD 20, the target of the monoclonal antibody rituximab. Therapy frequently combines rituximab with other chemotherapeutic agents. Administration of rituximab intravenously is well tolerated but frequently causes infusion reactions. Hematologic toxicity is seen less commonly but is well defined. Neutropenia, anemia, and thrombocytopenia have been described and often occur in the 10to 14-day window after rituximab infusion, similar to that seen with conventional chemotherapeutic agents. Isolated cases of acute severe thrombocytopenia after rituximab infusion for treatment of MCL have been reported, but this toxic event is uncommon. We identified 5 cases of acute severe thrombocytopenia occurring within 3 days of the administration of rituximab, suggesting that this toxic event might occur more frequently than previously recognized. Our series shows that acute severe thrombocytopenia is not always associated with infusion reactions, suggesting that the pathogenesis of these two toxic events might be different. Acute severe thrombocytopenia is reported more commonly in MCL than in other lymphomas treated with similar regimens. Four of the 5 patients received platelet transfusion. Subsequently, all the patients exhibited rapid recovery from thrombocytopenia without bleeding complications. Because acute severe thrombocytopenia appears to be transient, unpredictable, and not associated with bleeding complications, we would caution against the cessation or dose reduction of rituximab when treating MCL.

Pneumocystis jiroveci pneumonia (PJP) is associated with high morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Little is known about PJP infections after HSCT because of the rarity of disease given routine prophylaxis. We report the results of a Center for International Blood and Marrow Transplant Research study evaluating the incidence, timing, prophylaxis agents, risk factors and mortality of PJP after autologous (auto) and allogeneic (allo) HSCT. Between 1995 and 2005, 0.63% allo recipients and 0.28% auto recipients of first HSCT developed PJP. Cases occurred as early as 30 days to beyond a year after allo HSCT. A nested case cohort analysis with supplemental data (n=68 allo cases, n=111 allo controls) revealed that risk factors for PJP infection included lymphopenia and mismatch after HSCT. After allo or auto HSCT, overall survival was significantly poorer among cases vs controls (P=0.0004). After controlling for significant variables, the proportional hazards model revealed that PJP cases were 6.87 times more likely to die vs matched controls (P

BACKGROUND: The treatment for prostate cancer patients with biochemical failure after local therapy remains controversial. Peripheral androgen blockade using a combination of a 5-alpha reductase inhibitor and an antiandrogen may allow control of the prostate-specific antigen (PSA). Because testosterone levels are not suppressed, this approach may be associated with less morbidity than conventional gonadal androgen suppression. METHODS: All patients had undergone previous definitive local therapy and had evidence of a rising PSA >1ng/mL, with no evidence of recurrent disease. Patients received both finasteride, 5 mg orally per day, and flutamide, 250 mg orally 3× a day. Patients were followed for a PSA response and quality of life assessment. RESULTS: Ninety-nine of 101 accrued patients were eligible. A ≥80% PSA decline was seen in 96 (96%) patients. The median time to PSA progression was 85 months. With a median follow-up of 10 years, the median survival time had not been reached, and the 5-year overall survival rate was 87%. Toxicity was mild, with 18 patients stopping for toxicity; 15 had diarrhea, 4 had gynecomastia, and 3 had transaminase elevation. Baseline Functional Assessment of Cancer Therapy Prostate Module and Treatment Outcome Index scores decreased by 5 points each at 6 months after enrollment. CONCLUSIONS: The use of the finasteride/flutamide combination is feasible, and results in PSA declines of ≥80% in 96% of patients with serologic progression after definitive local therapy. There were no unexpected toxicities, and the change in quality of life was mild. Further evaluation of this or a similar regimen in a controlled clinical trial is warranted. Cancer 2012. © 2011 American Cancer Society.

We prospectively treated 80 patients with relapse of malignancy or secondary myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with allogeneic HCT (allo-HCT) using a reduced-intensity conditioning regimen of fludarabine 150 mg/m2 plus intravenous busulfan 6.4 mg/kg. Both matched sibling (MSD) and unrelated donors (MUD) were allowed. Patients transplanted from MUD donors received more intensive graft-versus-host disease (GVHD) prophylaxis, including rabbit antithymocyte globulin (ATG) 10 mg/kg, mycophenolate mofetil, and an extended schedule of tacrolimus. With a median follow-up of 3.1 years (0.9-5.8), treatment-related mortality (TRM) at 6 months and 2 years was 8% and 23%, respectively. Neither TRM nor the rates of acute GVHD (aGVHD) were different in those with sibling or MUD donors. Donor CD3 cell chimerism >90% at day +30 was achieved more often in patients with MUD than with matched sibling donors, 70% versus 23% (P < .0001). Median event-free suvival was higher in patients who achieved early full donor chimerism (14.2 versus 8 months, P = .0395). Allo-HCT using this reduced-intensity conditioning regimen can be performed with low TRM in patients who have received a prior AHCT. Efforts to improve early donor CD3 chimerism may improve event-free survival.

Untreated de novo (n=421) and secondary (n=189) acute myeloid leukemia (AML) patients≥60 years received intensified chemotherapy, including daunorubicin 60mg/m2 and etoposide 100mg/m2 during days 1, 2, 3 with cytarabine 100mg/m2 during days 1–7, with a second induction if needed and one consolidation course with these drugs and doses for 2, 2 and 5 days, respectively. In all, 287 (47%) achieved complete remission (CR), 136 (22%) died and 187 (31%) were non-responders. CR rates were 27, 44 and 52% for complex karyo-types, rare aberrations and neither (P

BACKGROUND: Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS included only a small number of patients with CMML. The objective of this study was to evaluate the efficacy and safety of azacitidine in the treatment of CMML. METHODS: The records of thirty-eight patients diagnosed with CMML and treated with azacitidine at our institution were reviewed. Azacitidine was administered at 75 mg/m2/day for 7 days or 100 mg/m2/day for 5 days every 4 weeks. Patients who received at least 1 cycle of the drug were considered evaluable for response. RESULTS: Response was assessed by the modified International Working Group (IWG) criteria. The overall response rate was 39% (14 of 36); complete response (CR) rate was 11% (4 of 36); partial response (PR) rate was 3% (1 of 36); hematologic improvement (HI) was 25% (9 of 36). The median overall survival was 12 months. There was a statistically significant overall survival advantage in responders compared with nonresponders: 15.5 months versus 9 months, respectively (P = .04). Treatment was generally well tolerated. One of 2 patients had complete resolution of a skin rash that was due to monocytic infiltration. CONCLUSIONS: Azacitidine is active in the treatment of CMML. The therapy-associated toxicity is acceptable. Our results support further investigation of azacitidine in CMML, particularly in combination with other agents. Cancer 2011;. © 2010 American Cancer Society.

Background. Hospital course of patients with hematologic malignancies associated with multiple complications, such as venous thromboembolism (VTE) which significantly affects morbidity and mortality. Compared to the general population patients with hematologic malignancies carry series of risk factors of VTE. Goals of this study were to describe demographic characteristics as well as define the risk factors of VTE in hospitalized patients with hematologic malignancies. Our study was focused on acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), Non-Hodgkin's lymphoma (NHL), Hodgkin's Disease (HD), multiple myeloma (MM). Methods. Cohort selection. The Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality (AHRQ) for the years 2011 to 2015 was queried for the analysis. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and corresponding ICD-10-CM codes (for the period of 0ctober 1 - December 31, 2015) in order to identify patients with hematologic malignancies as a primary diagnosis for the hospitalization, and VTE as secondary diagnosis of the hospitalization. In order to determine comorbidities in selected population we used Clinical Classifications Software (CCS) in conjunction with ICD-9-CM codes. Statistical Analysis. Complex weights were used throughout all calculations, enabling appropriate national projections. Percentages in all tables and figures reflect national estimates. Chi-squared and independent t-tests were used for univariate analysis where appropriate. We performed logistic regression analyses to examine the association between risk factor and VTE. In our study p-value Results. A total of 80,078 patients with hematologic malignancies were hospitalized from 2011 to 2015. Males represented 56.1% of the population, majority of the patients were white (69.5%), greater part of the patients were older than 35 years of age (35-65 42.6%, >65 48.8%) (Table 1). Main comorbidities during hospitalization were anemia (58.1%), followed by hypertension (49.1%), fluid disorders (40.1%) and coagulopathies (24.5%) (data not shown). Rate of VTE in all patients was 5.3% and was evenly distributed among genders and races. Rate of VTE was highest in patients with AML (6.6%) followed by ALL (6.1%), and NHL (6.0%), and lowest in patients with MM (3.49%) followed by CLL (3.31%), and CML (3.31%) (Table 2). The highest risk of VTE among patients with hematologic malignancies were in patients receiving chemotherapy (OR=1.684 95% CI=1.567-1.809) followed by infections such as pneumonia (OR 1.313 95% CI 1.201-1.436) and sepsis (OR=1.66 95% CI=1.524-1.621). Other comorbidities such as congestive heart failure, liver disease, coagulation disorders and acute renal failure were associated with significantly higher risk of VTE with OR varying from 1.1 to 1.2. (Table 3) Conclusions. In this retrospective large US inpatient database analysis, we found that average rates of VTE in patients with hematologic malignancies was 5.3% and was highest in patients with AML. Patients receiving chemotherapy had highest risk of developing VTE during hospitalization followed by patients with infections such as sepsis and pneumonia. Higher rates of VTE in patients receiving chemotherapy and patients with sepsis was previously described, however our findings indicate that rate of VTE remain high in these population. Findings of our study can be used for development of the appropriate antithrombotic prophylactic strategies in hospitalized patients with hematologic malignancies. Disclosures No relevant conflicts of interest to declare.

7043Background: Induction chemotherapy for AML results in prolonged neutropenia and a high risk of infection. CLT-008 is a human off-the-shelf allogeneic MPC preparation manufactured by ex vivo cul...

e19010Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APML). Anthracycline is added at induction for high ri...

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens for diffuse large B-cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, many patients develop refractory or recurrent DLBCL and then receive autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes following AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n=176, “+R” group) or was not (n=818, “ −R” group) administered with front-line or salvage therapy prior to AuHCT. The +R group had superior progression-free survival (50% versus 38%, p=0.008) and overall survival (57% versus 45%, p=0.006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Non-relapse mortality (NRM) did not differ significantly between the +R and −R groups. In multivariate analysis, the +R group had improved progression-free survival (relative risk of relapse/progression or death 0.64, p

Low-grade myofibroblastic sarcoma is a neoplasm of atypical myofibroblasts with fibromatoseslike features and a predilection for head and neck sites, including the oral cavity. These lesions have only been characterized in the last 2 decades, and controversies in the concept of neoplastic myofibroblasts still exist. Lack of obvious cytological atypia may result in their being mistaken for reactive fascitislike lesions or fibromatosis and architectural similarities to fibrosarcoma or leiomyosarcoma may complicate the diagnostic process. This paper describes a spindle cell neoplasm in a 40-year-old man that was diagnosed 9 years ago as an unclassifiable myofibroblastic proliferation. The recurrent tumor, which presented 6 years following excision of the original tumor, was subsequently classified as a low-grade myofibroblastic sarcoma. The morphological, immunohistochemical, and electron microscopic features of this unusual sarcoma and the most likely differential diagnoses are discussed.

There is no data on safety and efficacy of a second course of ibritumomab tiuxetan. In this work, data on patients with B-cell NHL who were treated with two courses of ibritumomab tiuxetan were analyzed. Eighteen such patients were analyzed (age: 58 years, 48 - 91), with a median of four prior regimens (1 - 7), stem cell transplantation (n = 5), and radiation therapy (n = 6). After the first course, G3/4 neutropenia and thrombocytopenia was 35% and 41%; overall response rate (ORR) was 89%; time between courses was 16.6 months (6.0 - 42.7). After the second course, the incidence of G3/4 neutropenia and thrombocytopenia was 28% and 44%; and ORR 77%. There were no infectious or bleeding complications, secondary myelodysplastic syndromes, or leukemias. Retreatment with the ibritumomab tiuxetan regimen was well tolerated, with a safety profile similar to that of the first course. To conclude, patients who benefited from the first course of ibritumomab tiuxetan can benefit from retreatment.

Patients older than 55 years of age with acute myelogenous leukemia (AML) are less likely to achieve complete remission and more likely to experience toxicity with conventional induction chemotherapy than younger patients. Azacitidine administered in the outpatient setting is well tolerated and can induce complete hematological remission in patients with myelodysplastic syndromes (MDS). At higher doses, azacitidine has activity in AML.Twenty patients were retrospectively identified who had been treated with azacitidine with bone marrow blast counts between 21 and 38%. Patients with blast counts up to 29% were initially treated as MDS, but by WHO now meet criteria for AML. Patients with blast counts over 29% were treated with azacitidine after being deemed poor candidates for induction chemotherapy. Azacitidine 75 mg/m2/day was administered subcutaneously for 7 days every 4 weeks, which was defined as 1 cycle.The overall response rate was 60% (12/20): complete response (CR; n = 4; 20%); partial response (PR; n = 5; 25%); hematologic improvement (HI; n = 3; 15%). The median survival of responders was 15+ months compared with 2.5 months for nonresponders (P = .009). During therapy, responders had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or 0. The most common toxic event was infection (n = 8). Four patients were hospitalized during the first cycle of treatment.Azacitidine administered in the outpatient setting can induce remission in AML. The therapy is well tolerated and might be an alternative for patients unlikely to tolerate standard induction chemotherapy.

This study examines whether malignant disease under treatment influences the incidence of cyclosporine or FK-506 neurotoxicity after myeloablative conditioning and allogeneic bone marrow transplantation (allo-BMT).Review of 290 patients who received myeloablative conditioning prior to allo-BMT and cyclosporine/FK-506 identified 21 (7.2%) patients with neurotoxicity confirmed by computed tomography or magnetic resonance. Underlying malignancy necessitating allo-BMT included leukemias (67%), lymphoma (10%), myelodysplastic syndrome (10%), and multiple myeloma (MM). Frequency of neurotoxicity by disease was compared.The highest incidence of neurotoxicity was present with MM (25%), whereas the lowest incidence was present with lymphoma (2.7%). Other diseases demonstrated intermediate incidence, including acute leukemias (10%), myelodysplastic syndrome (6.4%), and chronic myelogenous leukemia (4.9%).Cyclosporine/FK-506 neurotoxicity varied according to the underlying malignancy. The variable susceptibility to the development of neurotoxicity in this population may depend on the interaction of host vasculature with disease specific factors. Understanding the cause of neurotoxicity could improve survival after allo-BMT.

Purpose: Radioimmunotherapy (RIT) with yttrium-90 (90Y)-labeled anti-CD20 antibody (90Y ibritumomab tiuxetan; Zevalin, IDEC Pharmaceuticals Corporation, San Diego, CA) has a high rate of tumor response in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). This study presents the safety data from 349 patients in five studies of outpatient treatment with 90Y ibritumomab tiuxetan. Patients and Methods: Patients received rituximab 250 mg/m2 on days 1 and 8, and either 0.4 mCi/kg (15 MBq/kg) or 0.3 mCi/kg (11 MBq/kg) of 90Y ibritumomab tiuxetan on day 8 (maximum dose, 32 mCi). Patients were observed for up to 4 years after therapy or until progressive disease. Results: Infusion-related toxicities were typically grade 1 or 2 and were associated with rituximab. No significant organ toxicity was noted. Toxicity was primarily hematologic, with nadir counts occurring at 7 to 9 weeks and lasting approximately 1 to 4 weeks depending on the method of calculation. After the 0.4-mCi/kg dose, grade 4 neutropenia, thrombocytopenia, and anemia occurred in 30%, 10%, and 3% of patients, respectively, and after the 0.3-mCi/kg dose, these grade 4 toxicities occurred in 35%, 14%, and 8% of patients, respectively. The risk of hematologic toxicity increased with degree of baseline bone marrow involvement with NHL. Seven percent of patients were hospitalized with infection (3% with neutropenia) and 2% had grade 3 or 4 bleeding events. Myelodysplasia or acute myelogenous leukemia was reported in five patients (1%) 8 to 34 months after treatment. Conclusion: Single-dose 90Y ibritumomab tiuxetan RIT has an acceptable safety profile in relapsed NHL patients with less than 25% lymphoma marrow involvement, adequate marrow reserve, platelets greater than 100,000 cells/μL, and neutrophils greater than 1,500 cells/μL.

Patients with myelodysplastic syndromes (MDS) who were anemic and/or thrombocytopenic were treated with 5-azacytidine (5-AZA) at a dose of 75 mg/m(2) per day SQ x 7 days. This cycle was repeated every 28 days. Forty-eight patients who received at least one cycle of 5-AZA were evaluable for response. Hematological toxicity was mild and consisted of thrombocytopenia and leukopenia. Extramedullary toxicity was uncommon and consisted of pneumonia, arthralgia, diarrhea, and injection site irritation. Eighteen of the 46 transfusion dependent patients became transfusion independent (39%). Median duration of response was 7 months with three patients continuing beyond 2 years. French Anglo British (FAB) classification and the International Scoring System (ISS) did not predict response to 5-AZA. However, a decrease in the white blood cells (WBC) during the initial cycle of 5-AZA correlated with a higher response rate.

Acute myeloid leukemia (AML) patients aged ≥ 60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20-30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m(2)/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13-724 days). Grade 3-4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1-2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m(2)/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML.

Objectives : To provide information on the assessment and management of the nutritional needs of patients with severe neutropenia. Data Sources : Textbook chapters, research articles, and review articles. Conclusions : Malnutrition is a common result of high-dose chemotherapy treatment. Clinical outcomes are directly related to careful assessment, early intervention, and ongoing evaluation and monitoring in the severely neutropenic population. Implications for Nursing Practice : Early assessment, management, and psychological support are essential in meeting the needs of this patient population.

University of Kansas Medical Center, Kansas City, KansasOur objectives were to measure and compare plasminogen activator inhibitor levels(PAI-1) in primary adult thrombotic thrombocytopenic purpura (TTP) and in secondaryTTP associated with bone marrow transplantation (BMT)-TTP. PAI-1 antigen levels weremeasured by an enzyme linked immunosorbent assay on platelet poor plasma samplesobtained from patients at the time of diagnosis of the TTP disorder and from a group ofnormal volunteers. The samples were frozen at −70°C. Patients with TTP secondary tobone marrow transplantation had their grade determined by percentage fragmented cellsand lactate dehydrogenase levels. The primary TTP samples were contributed by inves-tigators in the multi-institutional North American TTP Group, and the bone marrow trans-plant samples were obtained from an adult bone marrow transplant program. Nineteenpatients with adult TTP, and 47 patients with bone marrow transplant-TTP were evaluated.Of the latter, 14 had Grade 2, 13 had Grade 3, and 20 had Grade 4 BMT-TTP. PAI-1 levelswere elevated compared to control volunteers in both primary adult TTP and BMT-TTP,P< 0.001. Levels did not differ from normal in Grade 2 BMT-TTP (median = 16 ng/ml;quartiles = 9–20). PAI-1 levels were similar in primary TTP (median = 32 ng/ml; quartiles= 25–51) and Grade 3 BMT-TTP (median = 35 ng/ml; quartiles = 19–48 ng/ml),P= 0.7.However, PAI-1 levels were significantly higher in Grade 4 BMT-TTP (median = 83 ng/ml;quartiles = 60–143) than Grade 3 BMT-TTP, and primary TTP,P< 0.001. PAI-1 levels arehigh in primary TTP and secondary bone marrow transplant-TTP (Grades 3–4). In con-trast, normal levels are seen in Grade 2 BMT-TTP, which is a self-limited disorder. There-fore, high PAI-1 levels may contribute to hypofibrinolysis in the pathogenesis of primaryTTP and of moderate to severe TTP (Grades 3–4) following bone marrow transplantation.Am. J. Hematol. 59:9–14, 1998.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon cutaneous lymphoma that has been proposed as a distinct clinicopathologic entity, but studies of SPTCL are limited. We studied the clinicopathologic, immunophenotypic, and genetic features of 11 SPTCLs. All cases had a variable admixture of pleomorphic small, medium, or large lymphocytes and histiocytes infiltrating the subcutis in a lobular panniculitis-like pattern. A granulomatous reaction was seen in three cases and erythrophagocytosis in four. Karyorrhexis and fat necrosis were present in all cases. Angioinvasion was seen in seven SPTCLs; four had areas of coagulation necrosis. All cases expressed T-cell-associated antigens (CD3epsilon, CD45RO, or CD43) and T-cell receptors (TCR); nine expressed alphabeta TCRs and two expressed gammadelta TCRs. T-cell receptor-gamma, TCRbeta, or TCRdelta genes were clonally rearranged in 8 of 10 cases studied. Both gammadelta SPTCLs expressed Vdelta2+ TCRs and were CD4-, CD8- and CD56+. CD56 was negative in seven of nine alphabeta SPTCLs and inconclusive in the other two. Six of nine alphabeta SPTCLs were CD8+; the CD4/CD8 phenotypes were indeterminate in the other three. Cytolytic granule-associated proteins were expressed by all SPTCLs (11 of 11 were TIA-1+, 4 of 4 were perforin+). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER-1) was negative in all cases. Most patients responded to systemic chemotherapy or local radiation therapy. Seven patients are alive: four without disease (19-73 months) and three with disease (32-72 months); four died: three of disease (3-25 months) and one without disease (42 months). We conclude that SPTCLs are clonal, EBV-, cytotoxic T-cell lymphomas derived from alphabeta T-cells or gammadelta T-cells. The gammadelta SPTCLs appear to be preferentially derived from the Vdelta2+ subset. Subcutaneous panniculitis-like T-cell lymphoma may be rapidly fatal or indolent; local therapy may be appropriate for some patients.

A multistep HDC regimen was designed as first-line chemotherapy for MBC. Twenty-four patients with MBC and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (5000 mg/m 2 ), and etoposide (1000 mg/m 2 ) (CyVP16), followed by granulocyte colony-stimulating factor (G-CSF). Peripheral blood stem cells (PBSCs) were collected. Subsequently patients received cyclophosphamide (6000 mg/m 2 ), thiotepa (500 mg/m 2 ) and carboplatin (800 mg/m 2 ) (CTCb) with hematopoietic rescue. Upon recovery from hematopoietic and gastrointestinal toxicity three cycles of doxorubicin (50 mg/m 2 ) and taxol (150 mg/m 2 ) were delivered. After CyVP16 42% of patients developed neutropenic fevers. There was one documented episode of bacteremia. Patients received CTCb 32 days after starting CyVP16. After CTCb the median number of days to ANC >5 × 10 9 /1 was 10 and to a platelet count >20 × 10 9 /1 was 14. Neutropenic fevers developed in 16 patients. There were no hemorrhagic episodes. A total of 69 cycles of doxorubicin and taxol were delivered (87% of planned). The median time from PBSC infusion to the first cycle was 38 days. The median time to the second cycle was 27 days and to the last cycle was 24 days. One patient developed congestive heart failure. Two episodes of neutropenic fevers were observed. No toxicity-related deaths were observed. Grafts are stable at 6 months post transplantation. This multistep regimen is feasible with acceptable toxicity.

The safety and antifungal efficacy of amphotericin B lipid complex (ABLC) were evaluated in 556 cases of invasive fungal infection treated through an open-label, single-patient, emergency-use study of patients who were refractory to or intolerant of conventional antifungal therapy. All 556 treatment episodes were evaluable for safety. During the course of ABLC therapy, serum creatinine levels significantly decreased from baseline (P or = 2.5 mg/dL at the start of ABLC therapy (baseline), the mean serum creatinine value decreased significantly from the first week through the sixth week (P < or = .0003). Among the 291 mycologically confirmed cases evaluable for therapeutic response, there was a complete or partial response to ABLC in 167 (57%), including 42% (55) of 130 cases of aspergillosis, 67% (28) of 42 cases of disseminated candidiasis, 71% (17) of 24 cases of zygomycosis, and 82% (9) of 11 cases of fusariosis. Response rates varied according to the pattern of invasive fungal infection, underlying condition, and reason for enrollment (intolerance versus progressive infection). These findings support the use of ABLC in the treatment of invasive fungal infections in patients who are intolerant of or refractory to conventional antifungal therapy.

The combination of busulfan and cyclophosphamide has seldom been employed as a conditioning regimen for patients with lymphoma. Twenty patients with relapsed or refractory lymphoma were treated with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BU/CY) followed by peripheral blood stem cell rescue in 19 patients or autologous bone marrow in one patient. There were 12 females and eight males, with a median age of 48 years (range 30-65). Four patients had Hodgkin's disease, and 16 patients had non-Hodgkin's lymphoma. Disease status at the time of BU/CY was: first relapse in 10 patients (four patients with chemosensitive disease and six patients with chemoresistant disease), primary refractory disease in six patients, and more advanced disease in four patients. Excessive treatment-related toxicity was not noted. There were no cases of interstitial pneumonitis, but three cases of veno-occlusive disease occurred. At 2 years, the estimated overall survival and event-free survival are 50% and 33%. We concluded that BU/CY seems to have sufficient antilymphoma activity, is devoid of excessive toxicity and warrants further investigation in this patient population.

Background This multicentre, single-arm, open-label phase 2 trial investigated the efficacy and safety of lenalidomide monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). Methods Patients received oral lenalidomide 25mg once daily on days 1–21 of each 28-day cycle for a maximum of 24months, until disease progression or development of unacceptable adverse events (AEs). The primary end-point was efficacy; safety was evaluated as a secondary end-point. This study was registered with ClinicalTrials.gov, number NCT00655668. Findings A total of 54 patients with PTCL were treated. The overall response rate was 22% (12 of 54), including complete response (CR) or unconfirmed CR (CRu) in 11% of patients; 31% of patients with angioimmunoblastic T-cell lymphoma (AITL) responded (CR/CRu in 15% of patients). The median progression-free survival and median response duration were 2.5 and 3.6months, respectively, in the intent-to-treat population, and 4.6 and 3.5months, respectively, in patients with AITL. Thrombocytopenia and neutropenia were the most common grade 3 or 4 haematological AEs, in 11 (20%) and 8 (15%) patients, respectively. Overall, 19 patients (35%) experienced at least 1AE leading to study dose interruption or reduction (commonly neutropenia or thrombocytopenia). Serious AEs were observed in 54% of patients and 12 patients died during the study; lymphoma progression ( n =6); and acute respiratory distress syndrome, dyspnea, lung infiltration, neutropenic sepsis, pneumonia and cerebral ischaemia ( n =1 each). Interpretation Lenalidomide exhibited single-agent activity in heavily pretreated patients with PTCL, particularly in patients with AITL. Future development is warranted in specific histologies, such as AITL, and in combination with chemotherapy or other agents considered active in PTCL. Funding Celgene Corporation.