Salvage of Primary Refractory Acute Leukemia (AL) with High-Dose Etoposide (VP) and Cyclophosphamide (CY) Followed by Early Stem Cell Transplantation (SCT): An Effective Treatment Strategy for AML but Not for All.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5152-5152
Author(s):  
Thomas J. Nevill ◽  
Asha Johny ◽  
Kevin W. Song ◽  
Julye C. Lavoie ◽  
Cynthia L. Toze ◽  
...  
Keyword(s):  
Pulmonary Hemorrhage ◽  
Patient Characteristics ◽  
High Dose ◽  
Entire Cohort ◽  
Predictors Of Response ◽  
Common Grade ◽  
Blast Cells ◽  
Group 5 ◽  
Wbc Count

Abstract Primary refractory AL has a poor prognosis although some patients (pts) can be salvaged with allogeneic SCT. Induction of complete remission (CR1) with conventional chemotherapy prior to conditioning and SCT may improve long-term event-free survival (EFS). Between 03/91 and 10/03, 59 adults with primary refractory AL (defined as >15% marrow blast cells on day 30 of induction) were treated with VP 2.4 g/m2 by 34 hr. IV infusion beginning on day 1 followed by CY 2.0 g/m2 IV daily on days 3, 4 and 5 with hyperhydration (3 L/m2/d) as bladder prophylaxis. Six pts received VP 3.0 g/m2 and 1 patient received CY 1.8 g/m2 x 4 days. The study included 39 males and 20 females with a median age of 41 years (range 17–60). Diagnoses were AML (42 pts), ALL (13 pts) and biphenotypic AL (4 pts). Eleven pts (19%) presented with a WBC count > 50 x109/L and MRC karyotype was favourable in 4 pts, intermediate in 34 pts and adverse in 20 pts; metaphase analysis failed in 1 patient. All AML pts had already received high-dose cytosine arabinoside (HIDAC) and either daunorubicin (DNR) (n=33) or mitoxantrone and VP (n=9). ALL pts had previously received DNR, vincristine and prednisone with (n=9) or without (n=4) L-asparaginase. Biphenotypic AL pts had been induced with HIDAC, DNR, vincristine and prednisone. Induction day 30 marrow blast count was > 40% in 35 pts (59%). The most common grade I/II non-hematologic toxicities of VP/CY were oral mucosal (44% of pts), GI (20% of pts) and hepatic (15% of pts); only one patient developed grade III/IV toxicity (pulmonary). Median time to recovery of ANC > 0.5 x109/L and platelets > 20 x109/L was 26 and 22 days, respectively. Three pts (5%) died prior to day 21 of VP/CY and were not evaluable for response (2 pts sepsis, 1 patient pulmonary hemorrhage). Twenty-four pts (43%) were also refractory to VP/CY but 32 pts (57%) entered CR1. Response rates were similar in AML (54%) and ALL/ABL (67%) (p=0.52) and analysis of baseline patient characteristics did not reveal any predictors of response to VP/CY. Twenty-nine of 32 CR1 pts proceeded to SCT (24 allogeneic, 5 autologous); five pts with AL refractory to VP/CY also underwent allogeneic SCT although all subsequently relapsed. Four of the autologous SCT pts relapsed with only one patient remaining alive in CR1. Estimated 5-year EFS for the entire cohort of pts is 23%. The only positive predictor of survival was male sex (p=0.03) and cytogenetic risk group did not influence outcome (p=0.69). In the allogeneic SCT group, 5-year EFS was 45% and was signficantly better for pts with AML (52%) compared to pts with ALL (14%, p=0.04). In conclusion, VP/CY is able to induce CR1 in the majority of pts with primary refractory AL. For pts with AML in CR1 that have a suitable donor, subsequent allogeneic SCT results in a favourable long-term EFS. Although pts with primary refractory ALL have a high CR1 rate with VP/CY, overall outcome for this subgroup remains poor.

scholarly journals CD19 CAR-T Cells Administered after High-Dose Cyclophosphamide Chemotherapy Induce Rapid Remissions of Chemotherapy-Refractory Acute B-Cell Leukemia with High Tumor Burden

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4909-4909
Author(s):  
Yongxia Hu ◽  
Lei Xiao ◽  
Zhao Wu ◽  
Yi Luo ◽  
Chengfei Pu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Patient Characteristics ◽  
Tumor Burden ◽  
High Dose ◽  
Car T Cells ◽  
Car T ◽  
Blast Cells ◽  
Peak Blood ◽  
Bone Marrow Blasts

Abstract Introduction Primary disease relapse remains the leading causeof death inadult acute lymphocytic leukemia (ALL) patients despite the availability of high-dose chemotherapy, targeted drugs and allogeneic hematopoietic stem cell transplantation. Relapsed or refractoryALL especially with high leukemia burden has very poor prognosis. Chimeric antigen receptor-modified T cells (CAR-T) targeting CD19 may overcome many limitations of conventional therapies and induce remission in patients with refractory disease. Patients and Methods Refractory or relapsed CD19+ ALL adult patients with more than 60% blast cells in the bone marrow at the time of evaluation were enrolled. Eligible patients underwent leukapheresis, and T cells were transduced with a Lenti-virus encoding a CAR construct composed of anti-CD19 scFV linked to 4-1BB and CD3¦Æ signaling domains. To enhance the activity of the transferred CAR-T cells, all patients received lymphodepleting chemotherapy with fludarabine (30mg/m2/day Days -4, -3, -2) and cyclophosphamide (1000mg/m2/day Days -3, -2) followed with 1x10E6 to 10x10E6 CD19CAR-T cells/kg 2 days later. The primary objective of the study was to evaluate the safety and anti-tumor activity of CD19CAR-T cells in ALL. Peripheral blood and bone marrow samples were collected for immunophenotypic, cytokine, and molecular studies at pre-specified times after CD19CART cell infusion. Results 2 patients were enrolled. The patient characteristics are listed in Table 1. All the 2 patients had once achieved complete remission, with MRD<0.01%. Patient 1 suffered from high-risk ALL and achieved CR after 3 courses of induction chemotherapy. Because of lung infection and liver disfunction, he could not receive the 4th chemotherapy. At the time of enrollment on our protocol, he relapsed with 66% blast cells in bone marrow. When the lymphodepleting chemotherapy ended, percentage of his marrow blast cells was 45%. 5x10E6/Kg CAR-T cells were infused. Except for B-cell depletion (Figure 1A, B), the most prominent toxicities included fevers, fatigue and chills (Table 1). The peak blood and bone marrow levels of CAR-T cells were 41.8% and 28.3% of CD3+ lymphocytes in day 8 respectively (Figure 1A). Detailed cytokine analysis showed marked increases of IL-6 and IFN-¦Ã (Figure 1C). Bone marrow blasts were 0.047% and <0.01% in day 8 and day 12 respectively. Patient 2 exhibited persistent chemotherapy refractory disease with 74% blast cells in the bone marrow following salvage chemotherapy. When the lymphodepleting chemotherapy ended, percentage of his marrow blast cells was 77%. 10x10E6/Kg CAR-T cells were infused. This patient suffered severe CRS with marked increases of IL-6 and IFN-¦Ã (Figure 1C). Administered with the IL6-receptor antagonist Tocilizumab she recovered from CRS soon. The peak blood and bone marrow levels of CAR-T cells were 83.65% and 75.34% of CD3+ lymphocytes in day 8 respectively (Figure 1B). Bone marrow blasts were <0.01% on day 8. Conclusion Our study revealed that CD19CAR-T cells could express robust expansion and anti-leukemia activity in relapsed and refractory ALL patients with high tumor burden. All the 2 patients achieved CR with negative MRD within 12 days after CART cell infusion. No uncontrollable clinical toxicities were manifested. The robust anti-leukemia activity of CD19CAR-T and high-dose CTX chemotherapy might contribute to the good therapeutic efficacy in our clinical trial. More patients will be enrolled in this trial and results will be reported in ASH meeting this year. Table 1. Patient characteristics Patient Age/sex Number of prior therapies Lymphodepleting chemotherapy Marrow blast Toxicities Pre-CAR Post-CAR 1 51y/M 3 Flu(30mg/m2/d -4 to -2) and CTX(1g/m2/d -3, -2) 66% <0.01% Fever Fatigue Chills Anorexia 2 29y/F 22 Flu(30mg/m2/day Days -4 to -2) and CTX(1g/m2/day Days -3, -2) 73% <0.01% Fever Fatigue Vomit Hypoxemia Hypotension Disclosures No relevant conflicts of interest to declare.

scholarly journals Mucosal Eosinophilia Is an Independent Predictor of Vedolizumab Efficacy in Inflammatory Bowel Diseases

2019 ◽  
Vol 26 (8) ◽  
pp. 1232-1238 ◽  
Author(s):  
Erin M Kim ◽  
Cara Randall ◽  
Renee Betancourt ◽  
Staci Keene ◽  
Amy Lilly ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Multivariable Analysis ◽  
Patient Characteristics ◽  
Predictors Of Response ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Negative Predictor ◽  
Colonic Biopsies

Abstract Background Peripheral and mucosal eosinophilia may be associated with more aggressive disease in inflammatory bowel disease (IBD) patients. Vedolizumab blocks T lymphocytes, eosinophil adhesion, and extravasation in the gastrointestinal tract. It is not known if mucosal eosinophilia is a predictor for the therapeutic efficacy of vedolizumab. Methods This was a retrospective cohort study of IBD patients with ileal or colonic biopsies who were off steroids before starting vedolizumab. Biopsies were rereviewed by pathologists, and mean eosinophil density was quantified. Patient characteristics and steroid-free clinical response 6 months after beginning vedolizumab were determined. Features were compared between nonresponders and responders, and multivariable logistic regression was performed to identify predictors of clinical response. Results Of 251 IBD patients starting vedolizumab therapy, 65 patients (48% Crohn’s disease, 52% ulcerative colitis) met inclusion criteria. All IBD patients not responding to vedolizumab were more likely to have a higher baseline mean eosinophil count (340 ± 156 vs 236 ± 124; P = 0.004), be previously exposed to an anti-TNF (96% vs 56%; P = 0.001), and be male (58% vs 28%; P = 0.02). Mean eosinophil counts were significantly increased in colonic biopsies in UC nonresponders (438 ± 149 vs 299 ± 145; P = 0.01). A similar trend was seen in CD nonresponders. On multivariable analysis, colonic eosinophil density and prior anti-TNF exposure—and the combination of both—were independent predictors of response. Conclusion In ulcerative colitis, colonic eosinophilia and prior anti-TNF exposure were independent predictors of 6-month clinical nonresponse to vedolizumab. Mucosal eosinophil density as a novel biomarker should be explored in larger patient cohorts. Aside from the previous anti-TNF exposure, eosinophil density in the colon of patients with UC is a negative predictor for a steroid-free long-term response to vedolizumab. The degree colonic eosinophilia may be a novel biomarker that should be further explored.

Assessment of corticosteroid (CS)-associated adverse events (AEs) with long-term (LT) exposure to low-dose prednisone (P) given with abiraterone acetate (AA) to metastatic castration-resistant prostate cancer (mCRPC) patients (Pts).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 169-169 ◽  
Author(s):  
Karim Fizazi ◽  
Kim N. Chi ◽  
Johann Sebastian De Bono ◽  
Leonard G. Gomella ◽  
Kurt Miller ◽  
...  
Keyword(s):  
Low Dose ◽  
Compression Fracture ◽  
Abiraterone Acetate ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Common Grade ◽  
Low Incidence ◽  
Grade 3

169 Background: AA is the prodrug of abiraterone, which inhibits CYP17A1 and testosterone synthesis and prolongs survival of mCRPC pts. A low dose of P is given when AA is administered to mCRPC pts. LT use of moderate-/high-dose CS has an established AE profile. We investigated whether LT use of low-dose P with or without AA led to CS-associated AEs. Methods: 2,267 mCRPC pts in COU-AA-301 and COU-AA-302 received 5 mg bid P, representing 2,006 pt-yrs of P exposure. 1,333 pts received AA + P. We utilized an inclusive Standardized MedDRA Queries–oriented approach to identify 112 preferred terms for known CS-associated AEs from both databases. CS-associated AEs during 3-mo exposure intervals and across all exposure to P were assessed. Results: The overall incidence of CS-associated AEs for any P exposure was 25%, 26%, and 23% for all pts, AA + P, and P alone, respectively. The incidence of grade ≥ 3 CS-associated AEs with any P exposure was 5%, 5%, and 4% for all pts, AA + P, and P alone, respectively. The most common grade ≥ 3 CS-associated AEs occurring in ≥ 0.1% of all pts were hyperglycemia (2%), cataract (0.4%), diabetes mellitus (0.4%), gastrointestinal hemorrhage (0.3%), adrenal insufficiency (0.1%), hip fracture (0.1%), melena (0.1%), and spinal osteoporotic compression fracture (0.1%). The overall incidence of weight increase (grade 1/2 only) was 4%, 4%, and 5% for all pts, AA + P, and P alone, respectively. Most were grade 1 (3.4%).When assessed by duration of exposure (3-mo intervals up to ≥30 mo), grade ≥ 3 CS-associated AEs fluctuated between 1% and 2%, but no discernable trend was observed. The observed change in weight from baseline showed no apparent increase over time. Conclusions: With over 2,000 pt-yrs of exposure, low-dose P given with or without AA is associated with an overall low incidence of CS-associated AEs. The frequencies of CS-associated AEs were low with increased duration of exposure to P. Clinical trial information: NCT00638690 , NCT00887198 .

Treatment of Panic Disorder

1990 ◽  
Vol 3 (4) ◽  
pp. 233-240
Author(s):  
Peggy E. Hayes
Keyword(s):  
Panic Disorder ◽  
Patient Characteristics ◽  
Panic Attacks ◽  
Patient Acceptance ◽  
High Dose ◽  
Individual Response ◽  
Drug Of Choice ◽  
Federal Food ◽  
Lifetime Prevalence Rate

In 1981, panic disorder was officially recognized as a separate illness and not merely a component of generalized anxiety disorder. Panic disorder is characterized by panic attacks or unpredictable episodes of sudden and overwhelming feelings of fear or terror. The disorder has a lifetime prevalence rate of 1.6% to 2%, being more common in women than men; many patients do not seek treatment. The majority of patients who have panic disorder develop severe anxiety and agoraphobia; comorbidity with depression occurs in approximately 33%. Panic disorder seems to be chronic with significant morbidity and mortality, including suicide, in patients who are untreated. Fortunately, panic disorder can be successfully treated using several drugs, including antidepressants, imipramine and phenelzine, and the benzodiazepine, alprazolam. It is anticipated that the Federal Food and Drug Administration (FDA) will soon approve the first antipanic drug, alprazolam (Xanax, Upjohn, Kalamazoo, MI). The drug of choice for panic disorder is determined by careful evaluation of several drug and patient characteristics. Although alprazolam has some distinct advantages over the antidepressants, including faster onset of therapeutic response and greater patient acceptance, the major problem is drug dependence and withdrawal, especially after high-dose, long-term use. Alprazolam should never be abruptly discontinued, but slowly tapered according to individual response. The pharmacist can play a valuable role in educating patients regarding the efficacy of drug treatment, risks and benefits of individual therapeutic agents, as well as the risks of untreated panic disorder.

scholarly journals FLT3 Mutation Increases Relapse Risk after Allogeneic Hematopoietic Cell Transplant for Acute Myeloid Leukemia in First or Second Complete Remission: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 322-322
Author(s):  
Abhinav Deol ◽  
Salyka Sengsayadeth ◽  
Madan Jagasia ◽  
Kwang W Ahn ◽  
Hailin Wang ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Patient Characteristics ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Mutation Status ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Flt3 Mutation ◽  
Flt3 Mutations ◽  
Wbc Count

Abstract Relapse after allogeneic hematopoietic cell transplant (HCT) remains a major cause of transplant failure. Patients (pts) with FLT3 mutated acute myeloid leukemia (AML) tend to have poor prognosis and are often referred for early HCT. We studied 511 patients to determine if FLT3 mutations impact transplant outcomes. Adults with a diagnosis of de-novo AML, with available FLT3 mutation status in first or second complete remission (CR) who underwent a human leukocyte antigen (HLA) matched sibling or unrelated donor (8/8 or 7/8) HCT after myeloablative (MAC), non-myeloablative (NMA), or reduced intensity conditioning (RIC) reported to the CIBMTR from 2008-2011 were included. Clinical outcomes following HCT for FLT3 positive and FLT3 negative AML pts were compared adjusting for significant patient-, disease-, and HCT-related variables. 511 pts met the inclusion criteria: 158 (31%) with FLT3 mutations. Median follow-up of survivors was 37 months (range, 12-65). Patient characteristics are shown in Table 1. The FLT3 mutated group had significantly higher white blood cell (WBC) count at diagnosis, more pts. with normal cytogenetics and more cycles of pre-HCT consolidation. Univariate analysis (Table 2) showed increased probability of relapse after HCT (log-rank p=0.01) in the FLT3 positive group but no significant differences in overall survival (OS) (log-rank p=0.13). There were no statistical differences in non-relapse mortality (NRM), relapse-free survival (RFS), or the cumulative incidence of acute and chronic GVHD. In multivariate analysis performed excluding the confounder “WBC count at diagnosis” FLT3 mutation status had a statistically significant negative effect on risk of relapse (P ≤ 0.05), but no effect on overall mortality. We could not address the differential impact of varying FLT3 mutations or interaction of other molecular aberrations with FLT3, in addition we did not have information about post relapse interventions. Encouragingly, nearly 50% of patients with FLT3 positive AML who underwent allogeneic HCT in CR were long-term survivors after allogeneic HCT. Though associated with augmented risks of relapse, FLT3 mutation status does not adversely impact long-term survival. Pre-emptive strategies using FLT3 inhibitors after HCT may reduce relapse risk and should be studied prospectively in order to improve outcomes of these high-risk patients. Table 1: Patient Characteristics FLT3 Negative (N=353) FLT3 Positive (N=158) Median Age (Range) 46 yrs (18-60) 47 yrs(18-60) Median WBC count * x109/L (Range) 10 (<1-344) 34 (<1-305) Cytogenetics* Normal 114 (32%) 102 (65%) Other 228 (65%) 51 (32%) Missing 11 (3%) 5 (3%) Disease Status CR1 252 (71%) 125 (79%) CR2 101 (29%) 33 (21%) Cycles of consolidations prior to HCT in CR1* 0 86 (34%) 24 (19%) 1 71 (28%) 49 (39%) ≥2 55 (26%) 40 (32%) Missing 30 (12%) 12 (10%) Donor Type 8/8 Sibling 150 (42%) 67 (42%) 8/8 Unrelated 165 (47%) 70 (44%) 7/8 Unrelated 38 (11%) 21 (13%) Conditioning Regimen MAC 302 (86%) 136 (87%) NMA/RIC 51 (14%) 21 (13%) * p ≤ 0.05 Table 2: Univariate Analysis of Outcomes at 3 years FLT3 Negative (N=353) FLT3 Positive (N=158) Relapse * (95% CI) 28% (24-33) 38% (30-45) Overall Survival (95% CI) 55% (50-60) 49% (40-57) * p ≤ 0.05 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract 2558: Outcomes of Children with Cardiomyopathy Listed for Heart Transplant: A Multi-Institutional Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Anne I Dipchand ◽  
David C Naftel ◽  
Brian Feingold ◽  
Robert Spicer ◽  
Delphine Yung ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Patient Characteristics ◽  
Good Survival ◽  
Optimal Timing ◽  
High Dose ◽  
Assist Device ◽  
Term Survival ◽  
Timing Of Death ◽  
Waitlist Mortality

BACKGROUND: Dilated (DCM), restrictive (RCM), and hypertrophic (HCM) cardiomyopathies (CM) in children have widely varying clinical courses and therapeutic options. For all types, heart transplant (HTx) offers a chance for long-term survival, but clinical outcomes following listing and predictors to guide in the optimal timing of listing have not been well defined. METHODS AND RESULTS: A multi-institutional, prospective, event-driven registry of pts<18 years of age listed for HTx from 01/93 to 12/05 (n=2,792) was used to compare outcomes of DCM (n=965; 84%); RCM (n=126; 11%); and HCM (n=63; 5%). Waitlist mortality for all pts was 12% with no difference by diagnosis (p=0.69). At listing, more DCM were Status 1 (p<0.0001), on high dose inotropes (p<0.0001), ventilated (p<0.0004), or on an assist device (VAD, p=0.0081). At the time of HTx, Status 1 (p<0.0001) or VAD (p=0.0003) were more common in DCM pts. Despite being more acutely unwell, overall survival from listing was higher in DCM pts (p=0.05), which was most dramatic for those listed in infancy (p<0.0001).[Fig ] Survival was particularly poor in RCM and HCM pts who were <1 yr of age at listing.[Fig ] Late (10 yr) survival post-HTx was also higher in DCM pts (82%) compared with RCM (76%) and HCM pts (65%, p=0.02). CONCLUSION: Children with CM awaiting HTx have a low waitlist mortality and good survival post-HTx with DCM pts demonstrating a consistent, modest survival advantage from listing. The relatively poor survival in select groups of RCM and HCM pts suggests the need for further study to better understand the causes and timing of death, timing of listing, and influence of patient characteristics on survival.s

High-dose cytarabine-mitoxantrone versus hyper-CVAD in adult acute lymphoblastic leukemia and Burkitt’s lymphoma: A single center experience of two induction regimens.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7076-7076
Author(s):  
Gurpreet Singh Lamba ◽  
Rahul Pawar ◽  
Abhishek Marballi ◽  
Sang-Joon Lee ◽  
Delong Liu
Keyword(s):  
Prognostic Factors ◽  
Retrospective Analysis ◽  
Medical Center ◽  
Lymphoblastic Leukemia ◽  
Randomized Study ◽  
Philadelphia Chromosome ◽  
Patient Characteristics ◽  
Rank Test ◽  
High Dose ◽  
Entire Cohort

7076 Background: This is a retrospective analysis of 111 newly diagnosed adult ALL patients treated between January 1994 and January 2012 at Westchester Medical Center. Methods: Patients received induction chemotherapy with either high dose mitoxantrone and high-dose Ara-c (HDAM, n=62) or Hyper-CVAD (n=49). The patient characteristics are summarized in the table. OS, CR duration and time to recurrence were estimated using the Kaplan-Meier product estimate methods and comparative study was conducted based on Log-rank test. Differences in CR rates by treatment and by prognostic factors were analyzed using Chi-squared test and Fisher’s exact test. Results: The CR rate was 85% in the HDAM group and 84% in the HyperCVAD group. The median OS was 22.7 months (m), (95% CI 15.3-38.3 m) for the entire cohort, 21.4 m (95% CI 13.3 - 35.5 m) for HDAM arm and 26.8 m (95% CI 11.7 - 63.3 m) for HyperCVAD arm. The OS for patients with Philadelphia chromosome positive or t(4,11) was 13.2 m (95 % CI 9.5 – 26.8 m). In an analysis of the entire cohort for differences in CR rates based on prognostic factors, WBC < 10,000 was the only favorable factor toward CR (p=0.049). Other prognostic factors including cytogenetics, cell type, age, LDH, were not statistically significant. Conclusions: HDAM and Hyper-CVAD appear to be comparable in CR induction and overall survival in this single institution retrospective analysis. These two regimens should be compared in a large multicenter randomized study. [Table: see text]

scholarly journals FK506 treatment in a Long-term chronic rejection rat model of small bowel transplantation

2010 ◽  
Vol 33 (3) ◽  
pp. 168 ◽  
Author(s):  
Yanfei Zhu ◽  
Wei Wei ◽  
Yousheng Li
Keyword(s):  
Small Bowel ◽  
Chronic Rejection ◽  
Small Bowel Transplantation ◽  
High Dose ◽  
Sham Operation ◽  
Term Survival ◽  
Group 4 ◽  
Group 3 ◽  
Group 5

Background: Although acute rejection (AR) can be significantly improved by effective immunosuppressants, such as FK506, chronic rejection (CR) remains a major hurdle to long-term allograft survival after small bowel transplantation, in part because the pathogenic mechanisms of CR are, as yet, unknown. The rat orthotopic small bowel transplantation (OSBT) model has been used by a few researchers, but without long-term survival. Methods: Rats were randomly divided into five groups: Group 1 (n=20), sham-operation rats; Group 2 (n=20), Lewis to Lewis; Group 3 (n=20), F344 to Lewis treated with FK506 (0.3 mg/kg/day); Group 4 (n=20), F344 to Lewis with FK506 (0.5 mg/kg/day); Group 5 (n=20), F344 to Lewis with FK506 (1.0 mg/kg/day). FK506 was administrated intramuscularly to recipients on postoperative days (POD) 0-13, 20 and 27. Body weight, survival rate and histology were measured. Results: Histopathological analysis revealed distinctive abnormalities of the allograft for all animals, including changes in villous architecture, interstitial fibrosis and intimal thickening; however, survival times were significantly increased with higher doses of FK506. Rats in Group 3 and Group 4 (low and moderate FK506 doses) survived 16-18 weeks, while recipients in Group 5 (high dose) survived 24-27 weeks. Conclusion: FK506 treatment (1.0 mg/kg/day, intramuscularly administrated to recipients on POD0-13, 20 and 27) can be used effectively to establish a rat OBST model of CR that will be useful for the study of the pathogenesis of CR and the effectiveness of various drugs.

Outcome of Patients with Acute Myeloid Leukemia Treated with Salvage High-Dose Cytarabine Monotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2543-2543
Author(s):  
Jonathan Canaani ◽  
Marlise R. Luskin ◽  
Alison Loren ◽  
Colleen Timlin ◽  
James Mangan ◽  
...  
Keyword(s):  
Research Funding ◽  
De Novo ◽  
Residual Disease ◽  
Single Agent ◽  
Patient Characteristics ◽  
High Dose ◽  
Refractory Disease ◽  
De Novo Aml ◽  
Wbc Count ◽  
Active Disease

Abstract Introduction Cytarabine in high doses (> 1 g/m2) is commonly combined with other cytotoxic chemotherapy agents to treat acute myeloid leukemia (AML) in the initial and salvage settings. Single-agent high dose cytarabine (HiDAC) is traditionally reserved for consolidation therapy for patients in remission. At our institution we also use single agent HiDAC to treat patients with active disease. We reviewed our experience to assess the outcomes. Methods We identified patients (pts) with AML diagnosed from 2009-2014 and treated at the Hospital of The University of Pennsylvania with anthracycline plus infusional cytarabine induction (7+3) who received subsequent single agent HiDAC for active disease. Pts included were those with evidence of residual leukemia on nadir biopsy after one cycle of therapy or those with refractory disease (positive nadir after 2 cycles of therapy or disease at the time of or within 30 days of count recovery). Comparisons of categorical covariates by subgroup were evaluated using the Fisher's exact test. Patients In total, 44 pts with median age of 54 (range 23-69) years were identified. Twenty-five (56%) pts had de novo AML, and 19 (43%) had AML secondary to prior myelodysplasia (MDS) or a myeloproliferative neoplasm (MPN). Twenty-two pts (50%) had unfavorable cytogenetics, 8 (18%) were FLT3 -ITD positive, and 4 (9%) were NPM1 mutant (Table 1). Indications for HiDAC salvage included positive nadir marrow or frankly progressive disease at day 14 of 1 (n=28) or refractory disease (n=16) Outcome Six pts (14%) died during index hospital admission for HiDAC therapy (5 from sepsis, 1 from multi-organ failure). Twelve (27%) pts achieved CR following HiDAC salvage and 4 (9%) achieved CRp. Pts with de novo AML were more likely to achieve a CR/CRp (11/24; 46%) compared to those with secondary AML (antecedent myeloid disorder or prior chemotherapy/radiation therapy) (5/20, 25%; p=0.037). CR/CRp rates were higher for pts with a white blood cell (WBC) count ≤10K/µL at initial diagnosis (50% vs. 20%; p=0.039). Pts treated for residual disease at first nadir were more likely to respond to HiDAC (n=13/28, 46%) than pts treated for refractory disease (3/16, 19%; p=0.104). Cytogenetic risk, age, presence of extramedullary disease, and FLT3 -ITD/NPM1 mutation status were not associated with response in this small sample (Table 2). No features predicted early mortality. Conclusion Our data suggest that pts with AML who received HiDAC therapy for active disease after 1-2 cycles of anthracycline plus infusional cytarabine induction have CR rates of 36% with single agent HiDAC with a 14% rate of early mortality. De-novo disease, initial WBC count < 10K/µL and treatment for residual disease at first nadir predict for a better response. Pts presenting with refractory disease are less likely to respond to this approach, consistent with previously published data with HiDAC combination regimens. HiDAC monotherapy for persistent AML following initial induction is a reasonable therapeutic option. Figure 1. Patient Characteristics Figure 1. Patient Characteristics Figure 2. Response to HiDAC monotherapy Figure 2. Response to HiDAC monotherapy Disclosures Loren: Merck: Research Funding. Mangan:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Frey:Novartis: Research Funding. Porter:Novartis: Patents & Royalties, Research Funding.

Late Platelets Recovery after Autografting (ASCT) in Patients with Acute Myeloid Leukemia (AML) Is A Prognostically Favourable Factor for Long-Term Remission

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4433-4433
Author(s):  
A. M. Carella ◽  
G Catania ◽  
R Varaldo ◽  
S Nati ◽  
A Congiu ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Conditioning Regimen ◽  
High Dose ◽  
High Dose Therapy ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Previously Treated ◽  
Late Recovery ◽  
Wbc Count

Abstract Althought favourable results with ASCT in patients with AML in first CR have been reported, there are no definitive data indicating that this approach is superior to chemotherapy alone. We have recently reviewed our 23 years experience with ASCT in AML in Genoa. From January 1984 to December 2007, 79 patients in first CR, aged 18–65 years, who did not have a sibling donor, were autografted. These patients had been previously treated in induction with Ara-C 200 mg/m2/d × 7 days and DNR 50 mg/m2/d × 3 days. Soon after, they had received consolidation therapy with 4 courses of DAT therapy (DNR 50 mg/m2/d1, Ara-C 200 mg/m2 c.i. day 2–5, thioguanine 80 mg/m2 days 2–5). Fifty patients were autografted with bone marrow and 29 patients with peripheral blood stem cells. High-dose therapy consisted of Cyclophosphamide and single dose TBI (n=50) or high-dose busulfan and cyclophosphamide (n=29). At a median of 11 years, 15 patients (19%) are still alive and well. At that time genetic aberrations combined or not with cytogenetics were not available; therefore we have retrospectively analyzed the patients according to age, sex, WBC count, time to CR and conditioning regimen. None of these factors was predictive for long-term remission. On the contrary, we found that late platelets recovery was predictive. The median time to recover platelets &gt; 50 × 109/L was 72 days (45–115 days) in long-term remission patients versus ≤ 30 days in the other patients who relapsed. During the presentation details of this retrospective study will be discussed. In conclusion, the late recovery of platelets after autografting is in our experience the most predictive factor for long-term remission duration in autografted AML patients.

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