bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trisomy 13 in patients with hematological malignancies
Authors: Santana-Davila R. , Ellliott M. , Hook C. , Kaufmann S. , Letendre L. , Pruthi R. , Tefferi A. , Van Dyke D. , Wiktor A. , Litzow M. R. 
Published: March 2020

7055 Introduction: Cytogenetic abnormalities have been shown to be the most important determinant of prognosis in patients with acute myeloid leukemia (AML). In AML, trisomy 13 has been placed in the intermediate prognostic category although recent reports associate it with a more dismal outcome. The number of cases reported in the literature are relatively few, we reviewed our experience with trisomy 13 in hematologic malignancies to determine its significance and prognosis. Methods: We conducted a clinicopathological review of cases seen in our institution from January of 1990 to October of 2006. Our cytogenetic records were searched for patients, who had a hematological disorder whose non-stimulated bone marrow karyotype was found to have trisomy 13 as a sole abnormality. In men the absence of the Y chromosome was not regarded as a separate abnormality. Results: A total of 27 patients were identified. The median age was 76 years (range 25–87), 22/27 were male. The number of cases and diseases identified were 15 with AML, 5 with a myelodysplastic syndrome, 4 with an uncategorized myelodysplastic/myeloproliferative disorder, 2 with acute lymphoblastic leukemia and 1 with a chronic myeloproliferative disorder. Of the AML group 7 were M0 according to the FAB classification, 2 patients were identified to have M4 and another two M2. A single case each of M1 and M6 was also identified. In these 15 patients, 9 underwent induction chemotherapy, which consisted of intermediate dose Ara-C in 3 cases, anthracycline plus Ara-C in 5 patients, and daunorubicin, vincristine and prednisone in 1. Another 3 patients were given palliative treatment. For the rest of the subjects the type of treatment was unknown. A CR was obtained in 6 patients, 1 patient underwent a myeloablative stem cell transplant. Death has occurred in 24 patients, the median survival of the entire group was 5.4 months. In the patients with AML the median survival was 4.7 months, of the patients who achieved a CR the median survival was 9.5 months. Conclusions: We describe one of the largest series reported to date of trisomy 13 in hematologic malignancies and found that trisomy 13 is associated with male gender and an older age at presentation, as well as a poor prognosis. In AML its presence is associated with an FAB-M0 phenotype and its occurrence should be regarded as a high-risk feature. No significant financial relationships to disclose.
A new prognostic score for patients with lower-risk myelodysplastic syndrome (MDS) allows the identification of a subset of patients with poor prognosis
Authors: Shan J. , Kantarjian H. , Pierce S. , Estey E. , Garcia-Manero G. 
Published: March 2020

7076 Background: Current prognostic models of MDS do not allow the identification of patients (pts) with lower risk disease and poor prognosis. Methods: We evaluated the characteristics of 898 pts with low or intermediate-1 disease by IPSS referred at MDACC from 1976 to 2005. Distributions of OS and progression-free-survival (PFS) were estimated by the method of Kaplan and Meier and compared between subgroups using the log rank test. Cox proportional hazards regression model was used to assess the ability of patient characteristics to predict OS and PFS, with goodness-of-fit assessed by Martingale residual plots, the Grambsch-Therneau test, Schoenfeld residual plots, and the likelihood ratio (LR) test. Multiple patient characteristics were evaluated including ferritin and β2- microglobulin, but these last two were not included in the multivariate model because their values were only known for a subset of patients.None of the patients had received chemotherapy prior to referral. Results: Median age was 66 years (range 16–94), and 65% had diploid cytogenetics. Only 88 pts (10%) transformed to AML and 388 (43%) had died. By multivariate analysis, characteristics associated with a worse OS were low platelets, anemia, older age, higher percent of marrow blasts and poor risk cytogenetics. Although not included in the model, higher ferritin (p=0.03) and β2-microglobulin (p=0.001) levels were associated with worse prognosis.These allowed the development of a scoring system in which patients could be grouped in 3 categories. Patients in category 1 (score less than 0.7) (n=22%) had a median survival of 69 months (95% CI 55-NA) and a 4-year OS of 67%, in category 2 (score 0.7–1.2) (n=40%) of 25 months (95% CI 18–31) and a 4-year survival of 28%, and in category 3 (score more than 1.2) (n=38%) of 17 months (95% CI 15–20), and a 4 -year survival of 12%. The model could segregate patients in each IPSS category (low and int-1). A subset of patients with intermediate-1 risk treated with decitabine could also be stratified by the model. Conclusions: This data indicates that it is possible to identify patients with lower-risk MDS and poor prognosis that may benefit from early therapeutic intervention. No significant financial relationships to disclose.
Tolerability and hematologic improvement assessed using three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes
Authors: Lyons R. M. , Cosgriff T. , Modi S. , McIntyre H. , Beach C. L. , Backstrom J. T. 
Published: March 2020

7083 Background: At a dosing schedule of 75 mg/m2/day SC for 7 days every 4 weeks, azacitidine is an effective and safe treatment (Tx) for patients (pts) with myelodysplastic syndromes (MDS) (JCO 2002; 20:2429). An alternative dosing schedule that eliminates the need for weekend dosing would be more convenient to pts and clinicians. Methods: In this phase II, multicenter, open-label trial, pts with MDS were randomized to 1 of 3 regimens that were repeated every 4 weeks: AZA 5–2-2 (75 mg/m2/day × 5 days, followed by 2 days no Tx, followed by 75 mg/m2/day × 2 days), AZA 5–2-5 (50 mg/m2/day × 5 days, followed by 2 days no Tx, followed by 50 mg/m2/day × 5 days) or AZA 5 (75 mg/m2/day × 5 days). To determine if response/improvement according to International Working Group criteria (Blood 2000; 96:3671) can be maintained after 6 cycles, the study was amended to include a 12-month maintenance comparing AZA 5 every 4 weeks with AZA 5 every 6 weeks. Results: As of Nov. 30, 2006, 138 pts have been randomized to AZA 5–2-2 (n=46), AZA 5–2-5 (n=47) and AZA 5 (n=45). Most pts are RA (43%) or RAEB (30%), based on FAB classification. Of 104 pts who have received =2 cycles of Tx, hematologic improvement (major or minor in at least 1 cell line) occurred in 63% (65) of the patients ( Table ). Of these pts, 14% had a bi-lineage (AZA 5–2-2: 11%, AZA 5–2-5: 10%, AZA 5: 22%) and 6% had a tri-lineage AZA 5–2-2: 6%, AZA 5–2-5: 7%, AZA 5: 5%) response (based on any improvement). Ongoing pts in the study include AZA 5–2-2: 41% (19/46), AZA 5–2-5: 47% (22/47), and AZA 5: 58% (26/45). No treatment-related mortality has been reported. Most Tx-related grade 3 or 4 events were hematological (AZA 5–2-2: 39%, AZA 5–2-5: 24%, AZA 5: 16%). Updated data, including several pts who have completed at least 6 cycles maintenance, will be available at the time of the meeting. Conclusions: These data indicate that the 3 alternative azacitidine dosing schedules are safe, effective, and similar in efficacy with the FDA-approved regimen. [Table: see text] [Table: see text]
Evaluation of risk for development of myeloproliferative disorders, myelodysplastic syndromes, or acute leukemias with long-term eculizumab therapy in paroxysmal nocturnal hemoglobinuria (PNH) patients
Authors: Schubert J. , Young N. S. , Luzzatto L. , Brodsky R. A. , Socié G. , Rother R. P. , Rollins S. A. , Hillmen P. 
Published: March 2020

7087 Background: PNH is a rare bone marrow failure disorder defined by stem cell clones with somatic mutations in the PIG-A gene. These mutations result in peripheral blood cells deficient in GPI-anchored proteins including complement inhibitors CD55 and CD59. Chronic lysis of PNH RBCs leads to severe anemia, life-threatening thrombosis, debilitating fatigue, and impaired quality of life. Previous studies have indicated an increased frequency of myeloproliferative disorders, MDS, and acute leukemias in PNH. In a previous retrospective analysis of 1,760 PNH patients, 6.8% developed either myeloid or lymphoid disorders and 1% developed acute leukemias. Eculizumab (Soliris) is a humanized antibody that prevents terminal complement activation. Long-term eculizumab treatment has been evaluated in 195 PNH patients (>250 patient years of exposure) and shown to significantly restore the endogenous PNH RBC clone resulting in improved anemia, as well as significant improvements in thrombosis, fatigue, and quality of life. Methods: Leukocyte clone sizes were assessed at baseline and 26 weeks for patients receiving eculizumab in the Phase III clinical trials (TRIUMPH and SHEPHERD) using flow cytometry. The frequency of MDS and leukemia was calculated as a percentage of the eculizumab-treated patients across all eculizumab trials. Results: PNH leukocyte clone size did not increase with eculizumab treatment (median 96.1% at baseline vs 95.5% at week 26; P=0.80, signed rank test) suggesting that inhibition of terminal complement does not destroy or result in the proliferation of PNH leukocyte clones. Additionally, the frequency of new MDS (1/195 patients, 0.5%) and CMML (1/195 patients, 0.5%) during the treatment period was not increased over that expected. The single case of CMML occurred in a patient previously diagnosed with and was attributed to high grade myelodysplasia. Conclusions: To date, eculizumab treatment of PNH patients does not increase the risk for the development of myeloproliferative disorders, MDS or acute leukemias. Patients on eculizumab will continue to be followed in a Global PNH Safety Registry. No significant financial relationships to disclose.
Improved risk assessment in B-cell chronic lymphocytic leukemia based on sex-specific molecular profiling
Authors: Tinhofer I. , Rubenzer G. , Holler C. , Stoecher M. , Egle A. , Greil R. 
Published: March 2020

7090 Background: B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease with some patients having an indolent course and others a rapidly progressing one. As underlying molecular mechanisms of differential disease activity, genomic aberrations, the mutational status of the variable region of the immunoglobulin heavy chain (Ig VH) and distinct expression levels of Zap-70 and CD38 have recently been identified, and their capacity to interact with survival and proliferation signals of B-CLL cells has directly been linked to progression and response to therapy. Although male sex has also been identified as risk factor for a more aggressive disease in B-CLL, the molecular basis for this interaction remains elusive. Methods: We compared the prognostic value of the above-mentioned molecular risk factors between female (n=88) and male patients with B-CLL (n=116). Differences in their frequency was evaluated using the Chi-square test. Their impact on treatment-free and overall survival of patients was analyzed using the Kaplan-Meier method and the log-rank test. The prognostic value of each molecular risk parameter in female and male patients was determined using the Cox proportional hazards regression model. Results: High CD38 expression (=30%), unmutated Ig VH gene (=98%) and unfavorable genetic aberrations (i.e. del17p, del11q or tri12) detected in the neoplastic clone identified patients with significantly shortened treatment-free survival, irrespective of the sex of patients. In contrast, Zap70 expression in more than 20% of B-CLL cells was negatively associated with treatment-free survival only in female (RR: 3.5, 95% CI 1.5 –7.9, P=.003) but not in male patients (RR: 1.6, 95% CI 0.9 –2.9, P=.089). In addition, we identified high CD38 expression in T-cells as independent negative prognostic marker in male (RR: 2.8, 95% CI 1.5 –5.0, P=.0006) but not in female patients (RR: 1.9, 95% CI 0.8 –4.6, P=.17). Based on these results we developed a novel sex-adapted algorithm for improved risk assessment in B-CLL. Conclusions: We identified sex-specific differences in the prognostic value of Zap-70 and CD38 in B-CLL. Whether this can be explained by modulation of their specific signaling pathways by sex hormones will have to be addressed in future studies. No significant financial relationships to disclose.
Assessment of the hematopoietic cell transplantation comorbidity index in non-Hodgkin lymphoma patients receiving reduced intensity allogeneic hematopoietic cell transplantation
Authors: Pollack S. , Steinberg S. , Odom J. , Dean R. , Fowler D. , Bishop M. R. 
Published: March 2020

7096 Background: Several patient-related factors influence outcomes after allogeneic hematopoietic cell transplantation (HCT). The Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), a weighted index of 17 pre-transplant comorbidities, has been validated in non- myeloablative HCT studies, but it has not been tested in non-Hodgkin's lymphoma (NHL) patients receiving reduced-intensity conditioning (RIC) HCT nor has it been compared with a number of other pre-transplant factors. Methods: We performed an analysis of 63 NHL patients treated with RIC HCT to assess the HCT-CI's impact on overall survival (OS), treatment-related mortality (TRM) and disease-related mortality (DRM). Individual factors, including performance status, single comorbidities, CD34 dose, prior chemotherapy number, pre-transplant induction chemotherapy response, and NHL histology, were also analyzed relative to their impact on OS. Prior to transplant, all patients received an identical induction regimen (EPOCH-fludarabine). All patients received identical RIC (Cy/Flu) and were transplanted from HLA-matched siblings. Results: In univariate analysis, each of the above factors, except for histology and CD34 dose, exhibited a trend toward an association with OS (adjusted p<0.10). The HCT-CI (0–2 comorbidities vs. 3+ comorbidities) demonstrated an association with TRM at 100 days (4.5% vs. 26.3%) and 1 year (13.6% vs. 36.8%) post-transplant, but not DRM. The factor most strongly associated with OS was response to induction chemotherapy (CR/PR/SD vs. PD; p=0.0025). In a Cox model for OS, induction chemotherapy response remained the sole important factor, while the HCT-CI and other pre-transplant factors added little predictive value to the induction chemotherapy response. The HCT-CI was more strongly associated with OS and TRM in a subset analysis restricted to patients in CR/PR following induction chemotherapy. Conclusions: These findings suggest that the HCT-CI may be useful for estimating probabilities of TRM and OS in NHL patients being considered for RIC HCT. The data further suggest that chemotherapy response at transplant may have significant impact on transplant outcomes. No significant financial relationships to disclose.
Phase II non-randomized trial using pegfilgrastim for hematopoietic recovery after autologous peripheral stem cell transplantation
Authors: Patel S. A. , Sethi S. , Holter J. , Selby G. 
Published: March 2020

7101 Background: Filgrastim (FIL), granulocyte-colony stimulating factor(G-CSF) reduces time to neutrophil engraftment, hospital stay and antibiotic therapy but requires uncomfortable and inconvenient daily subcutaneous (SC) injections.Pegfilgrastim (PFIL), while more expensive, requires a single SC injection.Before changing our practice and for internal validation, we initiated phase II nonrandomized trial using PFIL instead of FIL for hematopoietic recovery after autologous peripheral stem cell transplantation(autoPBSCT).An interim analysis of this study was presented (Poster No: - 417) at 2006 BMT Tandem Meetings.Here we present a complete analysis of our study. Method: A Phase II nonrandomized trial compares a single injection PFIL 6mg SC on Day +1 to historical controls using FIL 5mcg/kg SC daily starting Day+7 and continued until ANC=500/mm3 for three consecutive days.Twenty-two patients prospectively(05/2005–06/2006) accrued (MM=2; NHL=13; HD=7, MM=Multiple Myeloma, NHL= Nonhodgkin's lymphoma, HD= Hodgkin's lymphoma).Sixty-six consecutive patients retrospectively (MM=21; NHL=25; HD=20) were analyzed as historical controls(04/1999–04/2005).This study has been completed and closed. The primary endpoint of this study was to determine the days needed to engraft neutrophils & platelet following PFIL administration after autoPBSCT. Wilcoxon Rank Sums test performed for all comparisons except gender comparison was done by chi-square test. Results: Use of a single convenient injection of PFIL resulted in earlier neutrophilic recovery, less packed red blood cell(PRBC) transfusion & shorter hospital stay. No PFIL patients required additional G-CSF. One patient had prolonged fever probably PFIL- related. Conclusion: Our phase II study indicates the equivalency of PFIL and FIL related to hematopoietic recovery after autoPBSCT. No significant financial relationships to disclose. [Table: see text]
Outpatient autologous stem cell transplants for selected patients with myeloma: Morbidity, mortality, and duration of hospitalization
Authors: Liu S. , Vogl D. T. , Chong E. A. , Luger S. M. , Porter D. L. , Schuster S. J. , Tsai D. E. , Andreadis C. , Nasta S. D. , Mangan P. A. , Stadtmauer E. A. 
Published: March 2020

7104 Background: High-dose melphalan with autologous stem cell support improves survival for patients with myeloma but often requires prolonged inpatient hospitalization. Short hospitalization with close follow-up may reduce complications, cost, and duration of total hospitalization for selected patients with good performance status and social support. Methods: We reviewed all initial autologous transplants for myeloma from 1/03–4/06, categorized by length of initial hospitalization as brief stay (≤4 days) or prolonged stay (≥5 days). Clinical selection for a brief stay had been based on a combination of age; cardiac, pulmonary, and renal function; performance status; availability of caregivers at home; distance from our medical center; and patient preference. We reviewed the post-transplant course to 100 days and calculated cumulative hospitalization by adding length of initial hospitalization to that of subsequent readmissions within 100 days. Results: 148 patients received an initial transplant for myeloma: 64 were selected for brief stay and 84 for prolonged stay. There were no significant differences in age or in renal function, Durie-Salmon stage, or B2-microglobulin at diagnosis. Brief stay patients were discharged home after stem cell reinfusion, with first follow-up scheduled 3–14 days later. Care at home included a nurse visit after discharge, intravenous fluids and ondansetron, and oral antibiotics, with blood work twice weekly. 46% of brief stay patients required readmission during the first 100 days and had a median of 8.5 cumulative hospital days post-transplant, as compared to 18 days for prolonged stay patients (p=0.0001). There were fewer documented infections among brief stay patients (29.7% vs 50.0%, p=0.01) and fewer admissions to intensive care units (0 vs 6.0%, p=0.047). The groups had similar rates of bleeding (1.6% vs 4.8%, p=0.3) and thrombosis (3.1% vs 8.3%, p=0.2). No patients in the brief stay group died within 100 days, while mortality in the prolonged stay group was 4.8% (p=0.08). Conclusion: Selected patients receiving an autologous stem cell transplant for treatment of myeloma can be managed with brief initial hospitalization and outpatient follow-up, with low morbidity and mortality. No significant financial relationships to disclose.
Monitoring plasma voriconazole levels may prevent subtheraputic dosing in pediatric stem cell transplant (SCT) patients
Authors: Morris J. D. , Voskoboynik D. , Brown W. C. , Czarnecki S. , Morris C. L. 
Published: March 2020

7105 Background: Voriconazole is frequently used for prophylaxis and treatment of fungal infections during hematopoeitic stem cell transplant (SCT). Clinical studies demonstrate a poorer outcome when voriconazole concentrations are ≤0.5mcg/ml. Pediatric dosing schedules to achieve trough concentrations >0.5mcg/ml are not established. Methods: Retrospective analysis of voriconazole levels in 16 pediatric allogeneic SCT patients recieving fungal prophylaxis with oral or iv voriconazole. Ages ranged from 0.5 to 16 years, median 8 years. Serum levels were measured by high-performance liquid chromatography. Samples were obtained 5 to 7 days after start or change of voriconazole therapy. Ninety-eight total levels were evaluated. Results: Eight patients (50%) achieved a trough level > 0.5mcg/ml on the majority of samples tested at doses ranging from 3.5 to 10 mg/kg po q 12 hours. At constant dose there was a significant intra-patient variability in trough levels over time. Most patients failing to achieve adequate trough levels were below the median age (see table ). Changing to iv therapy in 3 patients with low trough levels after oral therapy did not improve the trough levels. Multi-time point measurements were > 0.5mcg/ml at 2 to 6 hours after oral dose, but fell to < 0.2mcg/ml by 12 hours in 3 patients tested. Of 98 voriconazole levels, 52 were ≤ 0.5mcg/ml and 74 were < 1.0 mcg/ml. Conclusions: Unlike reports in adult patients, we found that frequent monitoring of voriconazole levels was necessary in pediatric SCT patients due to intra-patient variability. Younger pediatric SCT patients may require more frequent dosing schedules to achieve trough levels. No significant financial relationships to disclose. [Table: see text]