Impact of G-CSF for Outcomes of Non-M3 AML Patients Who Were Treated By Anthracycline-Based Induction (7+3 regimen) Chemotherapies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4889-4889
Author(s):  
Ka-Won Kang ◽  
Yong Park ◽  
Dae Sik Kim ◽  
Se Ryeon Lee ◽  
Hwa Jung Sung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Febrile Neutropenia ◽  
Confidence Interval ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Solid Cancer ◽  
Therapeutic Group ◽  
High Dose Cytarabine ◽  
The Impact

Abstract Granulocyte colony-stimulating factor (G-CSF) has been known to reduce the duration of neutropenia and the incidence of infection-related death in patients with solid cancer who were treated by cytotoxic chemotherapies. A few randomized trials addressed these benefits in patients with non-M3 acute myelogenous leukemia (AML). However, long-term effects of G-CSF exposure in these patients were not reported. We analyzed the impact of G-CSF for outcomes of non-M3 AML patients who were treated by anthracycline-based induction and high-dose cytarabine consolidation chemotherapies. The patients enrolled in the Korea University AML registry from September 2002 to December 2014 were analyzed. AML patients who were treated by anthracycline-based inducton (7+3 regimen) and high-dose cytarabine consolidation (cytarabine 3g/m2 q 12 hours on D1, 3, 5) chemotherapies were included for this analysis. Patients with acute promyelocytic leukemia were excluded. The enrolled patients were classified into 3 subgroups based on G-CSF administration strategies during induction chemotherapies; 1) patients without G-CSF exposure during induction (no G-CSF group), 2) patients with G-CSF administration which was initiated immediately after development of neutropenia (absolute neutrophil counts < 1000) but before development of febrile neutropenia (preemptive group), 3) patients with G-CSF administration which was initiated after development of febrile neutropenia (therapeutic group). 285 patients were included in this analysis. The median follow-up duration was 18 months. The number of no G-CSF, preemptive and therapeutic group were 83, 70, and 132, respectively. The impacts of G-CSF administration strategies for treatment outcomes were summarized in table 1. The incidence and duration of chemotherapy-induced febrile neutropenia (CIFN) was not statistically different in no G-CSF group and preemptive group (p=0.700 and p=0.103, respectively). According to the median duration of neutropenia, preemptive G-CSF group (20.5 days) showed marginal benefit compared to the other groups (24 days in no G-CSF group and 23 days in therapeutic group) (p=0.052). The median time to ANC recovery (>1000) was significantly shorter in preemptive group (23 days) and therapeutic group (23 days) compared to no G-CSF group (27 days) (p<0.001). Infection-related mortality was significantly lower in preemptive group (2.9%) compared to no G-CSF group (9.6%) and therapeutic group (15.9%) (p=0.020). Complete remission rate and cumulative incidence of relapse were not significantly different between groups (p=0.151 and p=0.423, respectively). In multivariate analysis for incidence of CIFN, quinolone prophylaxis was independently significant factor for reducing the incidence of CIFN (HR 0.222, 95% confidence interval 0.054-0.911, p=0.037). In multivariate analysis for infection-related death, young age (°Â60) and preemptive group were independently significant factors for reducing the development of infection-related death (HR 0.284, 95% confidence interval 0.120-0.676, p=0.004 and HR 0.108, confidence interval 0.012-0.934, p=0.043 respectively). According to the survival, there were no significant differences among groups in overall survival and relapse free survival (figure 1). Preemptive G-CSF administration during induction treatments in non-M3 AML patients was considered to be effective in reducing infection-related deaths without affecting remission, relapse and overall survival. Because quinolone prophylaxis was showed to be effective in reducing the incidence of CIFN, combination of preemptive G-CSF administration and quinolone prophylaxis might be considered to provide synergistic benefit in non-M3 patients with intensive chemotherapy. Disclosures No relevant conflicts of interest to declare.

European MCL Network: An Update on Current First Line Trials.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 388-388 ◽  
Author(s):  
Martin H. Dreyling ◽  
Eva Hoster ◽  
Olivier Hermine ◽  
J.C. Kluin-Nelemans ◽  
Jan Walewski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Febrile Neutropenia ◽  
Elderly Patients ◽  
Response Rate ◽  
Response Rates ◽  
High Dose ◽  
High Dose Cytarabine ◽  
The Impact ◽  
Grade Iii

Abstract Background: Conventional chemotherapy achieves only short term remission despite high initial response rates of 70%–80%. In the current study generation, the European MCL Network investigates the impact of various combined immuno-chemotherapy regimens. Additionally, in elderly patients the role of rituximab maintenance is being evaluated, whereas in younger patients dose-intensified regimens with implementation of high dose cytarabine are investigated based on the excellent results of the HyperCVAD regimen. Methods: In MCL elderly, patients are initially randomized between 8 cycles of R-CHOP or 6 cycles of R-FC (experimental arm). Patients who achieve either an PR or CR, receive subsequently either interferon maintenance (standard arm) or a single rituximab dose every 2 months. In MCL younger, the standard arm (R-CHOP induction followed by myeloablative consolidation: 12 Gray TBI, 2x 60mg/kg cyclophosphamide) is compared to the implementation of high dose cytarabine into induction (R-CHOP/R-DHAP) and consolidation (10 Gray TBI, 4x1,5 g/m2 Ara-C, 140mg/m2 melphalan). Results: In MCL elderly, 222 of 263 patients were evaluable based on the annual interim analysis. Median age was 70 years with 66% of patients displaying an intermediate high/high risk IPI. Induction was well tolerated with mainly hematological toxicity (grade III/IV in R-CHOP/R-FC): Leukocytopenia 62/72%, thrombocytopenia 13%/40%, but only rare febrile neutropenia (23%/7%) or infections (19%/23%). Despite the poor risk profile, combined immuno-chemotherapy (total group) achieved a remarkable 84% response rate (51% CR/CRu). Although the impact of maintenance is not yet evaluable, both progression-free and overall survival were encouraging with 77% and 86% at 12 months, respectively. In MCL younger, 247 of 271 patients were evaluable. Again, toxicity (grade III/IV in R-CHOP/alternating R-DHAP) was mainly hematological: leukocytopenia 58/77%, thrombocytopenia 14%/74%, but only rare febrile neutropenia (11%/22%) or infections (5%/7%). Combined immuno-chemotherapy achieved a 93% response rate (60% CR/CRu) before subsequent high dose consolidation. Again, both progression-free and overall survival are remarkable with both 90% at 12 months, respectively. Discussion: Combined immuno-chemotherapy results in high response rates in two prospective international trials. Further recruitment and follow-up will determine the role of rituximab maintenance and high dose cytarabine in this distinct subtype of malignant lymphoma.

High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency.

1997 ◽  
Vol 15 (2) ◽  
pp. 833-839 ◽  
Author(s):  
G A Smith ◽  
L E Damon ◽  
H S Rugo ◽  
C A Ries ◽  
C A Linker
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Univariate Analysis ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Once Daily ◽  
Dose Modification ◽  
Daily Schedule ◽  
High Dose Cytarabine ◽  
The Impact

PURPOSE To determine the impact of high-dose cytarabine (ARA-C) (HDAC) dose modification, based on renal function, on the incidence of neurotoxicity (NT). PATIENTS AND METHODS We retrospectively analyzed the records of 256 patients treated with HDAC (> or = 2.0 g/m2 per dose) for acute myelogenous leukemia (AML) at the University of California, San Francisco (UCSF). From 1985 to 1994, a total of 358 cycles of HDAC were administered, using either a twice-daily schedule (n = 208) or a once-daily regimen (n = 48). In 1989, a dose-modification algorithm was initiated at our institution, which reduced ARA-C doses in the setting of renal insufficiency (RI). For patients with a serum creatinine (Cr) level of 1.5 to 1.9 mg/dL during treatment, or an increase in Cr during treatment (deltaCr) of 0.5 to 1.2 mg/dL, ARA-C was decreased to 1 g/m2 per dose. For patients with a Cr > or = 2.0 mg/dL or a deltaCr greater 1.2 mg/dL, the dose was reduced to 0.1 g/m2/d. RESULTS Overall, the incidence of NT was 16% (34 of 208) for patients treated with twice-daily HDAC and 0% (none of 48) for patients treated with daily HDAC (P = .003). NT occurred more often in patients treated on a twice-daily schedule with 3 g/m2 per dose compared with 2 g/m2 per dose (25% v 8%; P = .009). NT occurred in 55% of the twice-daily-treated patients with RI, compared with 7% of those with normal renal function (P = .00001). In patients with RI, NT occurred in none of 11 dose-modified cycles versus five of 11 (45%) total unmodified cycles (P = .01). None of 14 patients treated with once-daily HDAC given during RI developed NT, compared to 55% of patients (23 of 42) receiving twice-daily HDAC during RI (P = .009). By univariate analysis, NT was not associated with patient age or serum alkaline phosphatase, but NT was significantly increased in patients treated with twice-daily HDAC when the serum bilirubin was > or = 2.0 mg/dL compared with twice-daily HDAC given when the total bilirubin was less than 2.0 mg/dL (33% v 14%; P = .017). Multivariate analysis confirmed that RI was the most significant risk factor associated with the development of NT. CONCLUSION HDAC NT is strongly associated with RI. The risk of HDAC NT can be reduced by the following: (1) routinely reducing the ARA-C dose from 3 to 2 g/m2 per dose; (2) modifying the ARA-C dose based on daily Cr values; and (3) administering HDAC on a once-daily rather than twice-daily schedule.

Graft-Versus-Host Disease (GVHD) and Survival Outcomes after HLA-Haploidentical (Haplo) Bone Marrow Transplant (BMT) Compare Favorably with Matched Related Donor (MRD), and Matched Unrelated Donor (MUD) BMT Utilizing High-Dose Posttransplantation Cyclophosphamide (PTCy)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 730-730 ◽  
Author(s):  
Shannon R. McCurdy ◽  
Christopher G. Kanakry ◽  
Yvette L. Kasamon ◽  
Javier Bolanos Meade ◽  
Hua-Ling Tsai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Chronic Gvhd ◽  
Lower Probability ◽  
Survival Outcomes ◽  
High Dose ◽  
Grade Ii ◽  
The Impact ◽  
Grade Iii

Abstract Background: High-dose PTCy has been shown to effectively reduce acute (a) and chronic (c) GVHD after MRD and MUD BMT and to enable the safe implementation of haplo BMT. However, GVHD-related risk factors and survival outcomes, the impact of donor type, and novel composite endpoints, such as cGVHD-free relapse-free survival (cGFRFS), have not been fully characterized in BMT with PTCy. Methods: We retrospectively analyzed 582 consecutive adult pts with advanced or poor-risk hematologic malignancies who received allogeneic BMT with PTCy at Johns Hopkins from 2002-2012. All pts received a T-cell replete bone marrow graft and PTCy (50 mg/kg/d IV) on D+3 and +4. Platforms consisted of: 1) myeloablative conditioning (MAC) with Busulfan/Fludarabine or Busulfan/Cy followed by MRD (n = 193; 33%) or MUD (n=119; 20%) allografting and PTCy as sole GVHD prophylaxis; or 2) nonmyeloablative (NMA) conditioning with Fludarabine/Cy/TBI followed by related haplo (n = 270; 46%) allografting and PTCy, mycophenolate mofetil D5-35, and tacrolimus D5-180. Results: The median follow up was 4 (range 0.3-11.4) years (y). The median pt age at time of BMT was 49 (range 18-66) in the MAC cohort and 54 (range 18-73) in the NMA cohort. On competing risk analysis, the D200 probability of grade II-IV aGVHD was 27% after haplo, 37% after MRD, and 50% after MUD BMT, and grade III-IV aGVHD was 4%, 11%, and 14% respectively. The 3-y probability of cGVHD was 12% after haplo, 8% after MRD, and 19% after MUD BMT. On multivariate analysis adjusted for age and original disease risk index (DRI), MRD and MUD BMT were associated with a statistically significantly higher risk of grade II-IV and grade III-IV aGVHD compared to haplo BMT (each p ≤ 0.001). Compared to haplo BMT, MUD, but not MRD, BMT was also associated with a significantly higher risk of cGVHD (p = 0.009). On multivariate analysis, female into male allografting was independently associated with a higher risk of cGVHD (p = 0.007), whereas age and CMV serostatus of the pt and donor were not statistically significantly associated with risks of acute or chronic GVHD. Pts with grade II-IV aGVHD or cGVHD had a lower probability of relapse, but a higher probability of nonrelapse mortality (NRM) at 3 y compared to pts without GVHD. Among pts with GVHD, an HCT-CI score ≥ 5 was associated with significantly inferior overall survival compared to lower HCT-CI scores. Although MAC matched BMT was associated with less relapse risk than NMA haplo BMT, the 3-y probabilities of NRM, DFS, and overall survival were comparable between the transplant platforms (Table). On multivariate analysis adjusted for pt age and DRI, there were no statistically significant differences in DFS, OS, or cGFRFS in MAC related or unrelated BMT compared to NMA haplo BMT. Conclusions: High-dose PTCy safely modulates acute and chronic GVHD across multiple BMT platforms. The apparently lower risk of aGVHD after NMA haplo BMT with PTCy likely reflects the reduced conditioning intensity and longer duration of immunosuppression utilized. Despite the limitations inherent to a retrospective analysis, these data suggest that key outcomes after BMT with PTCy are comparable across donor types and conditioning intensities. Notably, in all these settings, 3-y estimates of cGFRFS appeared to approach those of DFS. Thus, PTCy may minimize the late morbidity and mortality of cGVHD and allow earlier implementation of novel posttransplantation strategies for relapse prevention. TableOutcomes of BMT with PTCy3-y probabilitiesNMA HaploMAC MRD*MAC MUD*NRM141717DFS384144OS495856cGFRFS313533 * p = NS for all comparisons to haplo BMT on multivariate analysis Disclosures Off Label Use: High-dose posttransplantation cyclophosphamide.

Impact of Smoking History on Pulmonary Metastasis-free Survival in Patients With Soft-tissue Sarcoma

2021 ◽  
Vol 1 (2) ◽  
pp. 89-94
Author(s):  
MASATAKE MATSUOKA ◽  
MASANORI OKAMOTO ◽  
TAMOTSU SOMA ◽  
ISAO YOKOTA ◽  
RYUTA ARAI ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Confidence Interval ◽  
Pulmonary Metastasis ◽  
Hazard Ratio ◽  
Smoking History ◽  
Free Survival ◽  
The Impact

Background/Aim: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. Patients and Methods: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. Results: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). Conclusion: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.

Salvage Autologous Hematpoeitic Stem Cell Transplants (AHSCT2) for Myeloma: Single Center Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4591-4591
Author(s):  
Bishoy Faltas ◽  
Jane L. Liesveld ◽  
Michael Becker ◽  
Jainulabdeen J. Ifthikharuddin ◽  
Gordon L. Phillips
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Conflicts Of Interest ◽  
High Dose ◽  
The Impact

Abstract Abstract 4591 Although the role of AHSCT1 is well established in multiple myeloma therapy, the role of the salvage (not “tandem”) AHSCT2 is less clear. However, most pts. undergo initial stem cell harvests with plans for eventual AHSCT2. To clarify the indications, the prognostic factors and the outcomes of AHSCT2 in relapsed myeloma, we analyzed our experience in 19 pts. (pts.) who underwent salvage AHSCT2 between the 1994–2008. Mean age at AHSCT1/2 was 54.58 (SD 7.96)/57.03 (SD 8.10) respectively; 15 (79.0%) were males. At the time of diagnosis, 7 (36.8%) pts. had ISS stage I, 6 (31.6%) stage II, 3(15.8%) stage III and in 3 (15.8%) the ISS stage could not be determined. Isotypes: IgG 11 (57.9%), IgA 4 (21.1%), 1 (5.3%) pt. had IgM and 3 (15.8%) had light chain myeloma. Cytogenetics were normal in 6 (31.6%), abnormal in 5 (26.3%) and unavailable for 8 (42.1%) pts. The most common therapy received prior to AHSCT1 was Vincristine/Adriamycin/Dexamethasone in 11 (57.9%) pts.; 7 pts. were exposed to novel agents. One pt. achieved complete response (CR), 15 (79.0%) pts. achieved partial response (PR) and 3 (15.8%) pts. had stable or progressive disease after receiving the initial treatment. All pts. proceeded to receive high dose therapy with Melphalan (MEL), 2 pts received fTBI in addition to MEL. Mean MEL dose was 190.00 mg/m2 (SD 23.01); 15 pts. received 200 mg/m2. All pts. received >2×10e6/kg of CD34+ cells in the first and second transplants. At D+100 after AHSCT1, responses were: 4 (21.1%) CR, 1 (5.3%) VGPR, 8 (42.1%) PR and 6 (31.6 %) with lesser responses. Therapy to prolong response or for salvage after AHSCT1 was given in all pts before AHSCT2, including Thalidomide in 6 (31.6%), Bortezomib in 4 (21.1%) and Lenalidomide in 2 (10.5) pts. Median time to progression after AHSCT1 was 318 days [95 % CI 110– 573]. Median interval between AHSCT1 and AHSCT2 was 896.74 days (SD: 698.34 days). At the time of AHSCT2, 4 (21.1%) were in PR, 15 (79.0%) had progressive disease. For AHSCT2, all pts. Received MEL, one pt. received MEL + Cytoxan and one pt. received MEL + Bortezomib. The median MEL dose/m2 was 175.56 (52.04).All pts. survived AHSCT2 to D+100, responses were as follows: 3 (15.8%) VGPR, 9 (47.4%) in PR; 7 (36.9) pts. had lesser responses. After AHSCT2, nine (47.4%) pts. had grade III toxicity and only one pt. had grade IV toxicity (avascular necrosis). Maintenance therapy after AHSCT2 included Bortezomib in 7 (36.8%) pts., Lenalidomide in 5 (26.3%) pts. and Thalidomide in 4 (21.1%) pts. After AHSCT2, the median overall survival (OS) was 658 days [95 % CI 326–1330] and progression free survival (PFS) after AHSCT2 was 237 days [95 % CI 121– 397] (Figure 1). OS probability at 6, 12, 24 months after AHSCT2 was 81.3, 75.0, 39.3 % respectively. For all pts., the median OS time (i.e. time from diagnosis to death or last follow-up) was 2187 days [95% CI 1413– 4126]. At the end of the follow up period, a total of 14 pts. had died. Causes of death were progression in 12 (63.2%) and sepsis in 2 pts. (10.5%). The number of previous lines of chemotherapy, interval between transplants, disease status at the time of AHSCT1/2, type of myeloma and MEL dose were not predictive of OS and PFS. In the multivariate analysis, only age by decade at AHSCT2 and male gender were independent predictors of OS after AHSCT2 (HR 4.037, P= 0.01), (HR 3.74, P=0.07) respectively. Similarly, in the multivariate analysis for PFS after AHSCT2, age at AHSCT2 was an unfavorable independent predictor (HR 3.48, P=0.009) whereas relapse free response more than 18 months after AHSCT1 was an independent favorable predictor (HR 0.198, P=0.007).Our results are consistent with the few studies examining the impact of salvage transplants for myeloma which report a median overall survival ranging from 20.7 to 38.1 months from the time of AHSCT2.We conclude that salvage AHSCT2 can positively impact PFS and OS but efforts to improve outcomes are mandatory.FigureSEQ Figure ≂,* ARABIC 1Figure. SEQ Figure ≂,* ARABIC 1 X-axis represents time from AHSCT2 in days. Y axis represents survival distribution. Blue line = OS, Red = PFS. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of overweightness and critical weight loss on overall survival in patients with hepatocellular carcinoma initially treated with chemoembolization

2019 ◽  
Vol 8 (2) ◽  
pp. 125-133
Author(s):  
Zhen-Xin Chen ◽  
Zhi-Wei Jian ◽  
Xi-Wen Wu ◽  
Jun-Cheng Wang ◽  
Jing-Yuan Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Weight Loss ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Confidence Interval ◽  
Initial Treatment ◽  
Critical Weight ◽  
Cox Regression Analysis ◽  
The Impact

Abstract Background The effects of overweightness and weight loss on the development and prognosis of hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to evaluate the impact of overweightness and weight loss on the survival of patients with intermediate/advanced HCC receiving chemoembolization as initial treatment. Methods We examined 1,170 patients who underwent chemoembolization as initial treatment for Barcelona-Clínic Liver Cancer stages B and C HCC at Sun Yat-sen University Cancer Center (Guangzhou, China) between December 2009 and May 2015. A baseline body mass index (BMI) of ≥23 kg/m2 was defined as overweight, and body-weight loss of ≥5.0% from baseline was defined as critical weight loss (CWL). Cox regression analysis was used to determine the association between overweightness or CWL and overall survival (OS). Results The median survival time was 16.8 (95% confidence interval, 13.9–19.7) months and 11.1 (95% confidence interval, 10.0–12.2) months in the overweight and non-overweight groups (log-rank test, P &lt; 0.001), respectively. Cox multivariate analysis identified overweightness as an independent protective prognostic factor for OS (P &lt; 0.001). Subgroup stratification analysis revealed a significant association between overweightness and survival among patients receiving further treatment (P = 0.005), but not in those not receiving further treatment (P = 0.683). Multivariate analysis showed that both overweightness and CWL were independent prognostic factors for OS among patients receiving further treatment. Conclusion Among patients with intermediate- or advanced-stage HCC initially treated with chemoembolization, overweightness was associated with longer OS. Furthermore, CWL was an independent adverse prognostic factor for OS in patients receiving additional treatment.

Treatment Outcomes and Prognostic Factors of Ifosfamide, Etoposide, Cytarabine, Methotrexate, and Dexamethasone (IVAMdex) Regimen As 3rd Line (2nd salvage) Chemotherapy in Patients with Relapsed or Refractory Non-Hodgkin's Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2685-2685
Author(s):  
Yong Park ◽  
Seh Jong Park ◽  
Seok Young Lee ◽  
Se Ryeon Lee ◽  
Hwa Jung Sung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Febrile Neutropenia ◽  
Confidence Interval ◽  
Treatment Outcomes ◽  
Performance Status ◽  
Univariate Analysis ◽  
Early Death ◽  
Salvage Chemotherapy ◽  
Line Setting

Abstract Abstract 2685 Although high dose chemotherapy with hematopoietic stem cell support is the current standard for patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), all patients are not eligible for this strategy. A portion of this patients experiences refractory or relapsing disease after first salvage. However there are few data for treatment outcomes in this group of patients. In this retrospective analysis we evaluated the efficacy of ifosfamide, etoposide, cytarabine, methotrexate plus dexamethasone (IVAMdex) regimen in 2nd salvage (3rd line) setting and analyzed the pretreatment factors for patients who would be beneficial for this 2nd salvage regimen. A total of 41 patients with relapsed or refractory NHL after 1st salvage chemotherapy were analyzed. All patients were treated with IVAMdex regimen which consisted of ifosfamide (1500 mg/m2 daily from day 1 to day 5), mesna (1500 mg/m2 daily from day 1 to day 5), etoposide (150 mg/m2 daily from day 1 to day 3), cytarabine (100 mg/m2 daily from day 1 to day 3), methotrexate (3 g/m2 on day 5), leucovorin rescue (100 mg/m2 daily from day 5 to day 7), and dexamethasone (40mg on day 1 to day 3). The response rate was assessed after a minimum of two courses of chemotherapy. Toxicity and survival were analyzed in all patients. The median age was 51 years. Performance 0–1 and 2 was 56% and 44%, respectively. 28 evaluable patients completed more than 2 cycles. 13 patients were not evaluated due to early death (n=10), death without response evaluation (n=2), and follow-up loss (n=1), respectively. The overall response was as follows: 9 complete remission (32%), 4 partial remission (14%), 2 stable disease (8%), and 13 progressive disease (46%). The median overall and progression-free survival was 185 days (95% confidence interval, 84 days to 285 days) and 119 days (95% confidence interval, 30 days to 207 days), respectively (Figure 1). Univariate analysis of pretreatment factors for overall survival showed increased LDH (p=0.001), presence of B symptom (p=0.001), chemosensitive disease to prior regimen (p=0.044), performance status 0–1 (p=0.003), and low/low-intermediate IPI group (p=0.017) were significant. Multivariate analysis by Cox regression method showed that increased LDH (p=0.028, harad ratio 3.47, 95% confidence interval 1.147 to 10.526) and performance status 0–1 (p=0.041, hazard ratio 0.35, 95% confidence interval 0.13 to 0.96) were independently significant factor for overall survival. Treatment-related mortality (TRM) was reported in 16 patients (39%) and the cause of all TRMs was infection associated with febrile neutropenia. Of these, 10 deaths (63%) occurred within 30 days after initiation of chemotherapy (early death). Univariate analysis of pretreatment factors for early death showed increased LDH (p=0.011) and presence of B symptom (p=0.017) were significant. However multivariate analysis by log-rank test did not show any independently significant factors for early death. In this study salvage chemotherapy with IVAMdex regimen in 3rd line setting showed moderate response with high toxicities. However, we discovered that there might be subgroup of patients who can benefit from this regimen and serum LDH level and presence of B-symptoms may be useful indicators in differentiating these patients. However, considering high toxicities, the strategy to prevent early death associated with febrile neutropenia should be required. It might include prophylactic G-CSF and antimicrobial agent administration. To draw the conclusion, validation should be warranted in prospective trial with large scale. Disclosures: No relevant conflicts of interest to declare.

Outcome after autologous transplantation in the terms of comorbidity for patients with lymphoproliferative diseases: Single center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19502-e19502
Author(s):  
Aleksandra Pivkova Veljanovska ◽  
Sonja Genco Genadieva-Stavrik ◽  
Zlate Stojanoski ◽  
Lazar Chadievski ◽  
Irina Panovska Stavridis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Relative Risk ◽  
Confidence Interval ◽  
Autologous Transplantation ◽  
High Dose ◽  
Karnofsky Performance Score ◽  
Cell Transplant ◽  
Lymphoproliferative Diseases ◽  
Karnofsky Score ◽  
The Impact

e19502 Background: Autologous stem cell transplantation (ASCT) improves survival in patients with myeloma and lymphoma but is associated with morbidity and nonrelapse mortality (NRM). Hematopoietic cell transplant comorbidity index (HCT-CI) was shown to predict risk of NRM and survival after allogeneic transplantation. We tested the utility of HCT-CI as a predictor of NRM and overall survival (OS) in patients undergoing ASCT. Methods: We analyzed outcomes of 220 patients after high-dose melphalan and high –dose anti lymphoma chemotherapy during year 2000 to 2015. Individual comorbidities were prospectively collected at the time of ASCT. The impact of HCT-CI and other potential prognostic factors, including Karnofsky performance score (KPS), on NRM and survival were studied in multivariate Cox regression models. Results: HCT-CI score was 0, 1, 2, 3, and >3 in 42%, 18%, 13%, 13%, and 14% of the study cohort, respectively. Subjects were stratified into 3 risk groups: HCT-CI score of 0 (42%) versus HCT-CI score of 1 to 2 (32%) versus HCT-CI score > 2 (26%). Higher HCT-CI was associated with lower KPS < 90 (33% of subject’s score of 0 versus 50% in HCT-CI score > 2). HCT-CI score > 2 was associated with melphalan dose reduction (22% versus 10% in score 0 cohorts). One-year NRM was low at 2% (95% confidence interval, 1% to 4%). On multivariate analysis, overall survival was inferior in groups with HCT-CI score of 1 to 2 (relative risk, 1.37, [95% confidence interval, 1.01 to 1.87], P = .04) and HCT-CI score > 2 (relative risk, 1.5 [95% confidence interval, 1.09 to 2.08], P = .01). Factors that affect OS in the autologous recipients among lymphoma and myeloma patients were: HCT-CI, Karnofsky score, number of CD34+ cells/kg and time from diagnosis until transplant (p<0.05). Factors that affect TRM/NRM were HCT-CI, ECOG, Karnofsky score and number of hospital days and body weight.(p<0.05). Conclusions: ASCT for MM and lymphoma is associated with low NRM, and death is predominantly related to disease progression. Comorbidity evaluation during autologous transplantation for lymphoproliferative diseases can be a useful tool in predicting transplant outcome.

Time to Post-Remission Therapy (PRT) Is an Independent Prognostic Factor for Relapse and Overall Survival in Adults with Acute Lymphocytic Leukemia (ALL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1883-1883 ◽  
Author(s):  
Anjali Advani ◽  
Tao Jin ◽  
Ramon Tiu ◽  
Giridharan Ramsingh ◽  
Christopher Lowe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Univariate Analysis ◽  
Independent Prognostic Factor ◽  
High Dose ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Poor Risk ◽  
The Impact

Abstract Only 30% of adults with ALL are cured. The identification of modifiable prognostic factors is important in designing future treatment paradigms, and improving the outcome of patients. PRT is integral in the treatment of ALL, and eradicates minimal residual disease (MRD) after complete remission (CR) has been achieved with induction chemotherapy (IC). Decreasing the time from the start of IC to the initiation of PRT may improve prognosis by eradicating MRD at an earlier stage, and preventing the development of resistant leukemic clones. The goal of this study was to retrospectively evaluate the impact of time from the start of IC to PRT, and determine whether or not this affects progression-free survival (PFS) and overall survival (OS). Methods: We retrospectively evaluated adults with newly diagnosed ALL treated at CCF between the years 1996–2005. 116 patients with ALL were seen. 57 patients were newly diagnosed and received IC and PRT. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of CR, OS, relapse after remission, and PFS. Only variables significant in the univariate setting were included in multivariate analysis. Results were summarized as the hazard ratio (HR) with 95% confidence intervals (CI). The following variables were used in the analysis: pre-treatment characteristics (age, WBC, cytogenetic (CG) risk group, LDH), time to WBC recovery (time from the initiation of IC to an ANC of 500 after IC), CD20 expression, and time from the initiation of IC to start of PRT. CG risk was defined by CALGB criteria. Results: Characteristics at diagnosis: median age of 38 years [range 16–72], median LDH 673 U/L [112–5753], and median WBC 17.8 × 103/L [1.2–364]. 33.6% of patients had poor risk CG, 22.4% normal CG, 15% miscellaneous, and 29% unknown. Most patients received a vincristine/prednisone based IC (88%). However, 12% received high dose cytarabine/mitoxantrone IC. The CR rate was 75.3% for patients age < 60, and 60% for age ≥ 60. Median disease-free survival was 20.2% at 5 years. The median time from IC to PRT was 7.0 weeks [4.1–17.0]. On univariate analysis, increased age and increased time to WBC recovery were associated with a lower CR rate. Age and time from IC to PRT (per week increase (PWI)) [HR 1.17(CI 1.04–1.32), p=0.009] were significant predictors for relapse after remission. Increased age, poor risk CG, and time from IC to PRT (PWI) [HR 1.13(1.02–1.25), p=0.024] predicted decreased PFS. All of these factors (including time to WBC recovery) predicted decreased OS, with time from IC to PRT (PWI) having a HR of 1.11[(1.01–1.23), p=0.039]. On multivariate analysis, there was a trend for longer time from IC to PRT (PWI) [HR 1.53(0.92–2.54, p=0.10] predicting decreased OS and increased chance of relapse (PWI) [HR 1.12(0.98–1.29), p=0.09]. When patients age > 60 and poor risk CG were excluded, time from IC to PRT (PWI) was the only factor associated with decreased OS [HR 1.34(1.08–1.67), p=0.009], PFS [HR 1.27(1.04–1.55, p=0.019)], and an increased chance of relapse [HR 1.26(0.99–1.61), p=0.06]. Conclusions: Strategies to improve the prognosis of ALL are needed. Time from IC to PRT is an independent prognostic factor for treatment outcome, and administering PRT on time may improve our outcomes in adult patients with ALL.

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