Phase II Study of Gemtuzumab Ozogamycin (GO) and Cytarabine (ARA-C) in Patients with High Risk MDS and AML..

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4723-4723
Author(s):  
Peter Kang ◽  
Karen Seiter ◽  
Delong Liu ◽  
Muhammad Arshad ◽  
Anila Qureshi ◽  
...  
Keyword(s):  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Complete Response ◽  
Lung Damage ◽  
Poor Performance Status ◽  
High Cumulative Dose ◽  
History Of ◽  
M 12 ◽  
To Receive

Abstract To evaluate the efficacy of GO + ara-c in high risk pts, we treated 22 pts with MDS (10) and AML (12) with cytarabine 100 mg/m2/d x 7 d and GO 9 mg/m2 x 1 on d 4. Pts with MDS were eligible if they had [1] RAEB-1 and either hgb < 8 gm/dl, platelet < 50,000/mm3, neutrophils < 1000/mm3, or cytogenetics other than 5q-, 20q-, -y, or normal, [2] RAEB-2, or [3] CMML. Pts with AML (newly diagnosed or relapsed) were eligible if they were ineligible for anthracycline-based therapy (poor performance status: 2 pts; low ejection fraction or high cumulative dose of anthracyclines: 6 pts, both reasons: 4 pts). The median age was 66, M:12, F:10. Diagnoses: RAEB-1: 4, RAEB-2: 5, CMML: 1, AML, newly dx’d: 7, AML relapsed: 5. Cytogenetics were high risk: 10, intermediate risk: 11 pts, low risk: 1 pt. Overall, 18% had a complete response (CR) after one cycle of therapy. Three pts (14%) had a partial response (PR), of which one had a CR after a second course of therapy. Of the pts with AML: CR: 2/12, PR: 2/12, Failure (F): 5/12, Toxic Death (TD): 3/12. For pts with MDS: CR: 2/10, PR: 1/10, F: 5/10, TD: 2/10. Toxicities included neutropenic fever/sepsis, mucositis, diarrhea, increased LFTs, hemorrhage. One pt with a history of ABVD and RT to chest for HD developed direct pulmonary toxicity due to chemotherapy (diffuse pulmonary infiltrates, biopsy proven toxic lung damage). Although overall response rate is modest, some pts had remarkable responses: One pt with RAEB-1, transfusion dependent and multiple high risk cytogenetics (−5, −7, multiple others) remains in CR (including cytogenetic CR) 7 months post treatment. A second pt with RAEB-1, transfusion dependent and multiple high risk cytogenetics (−5, −7, multiple others) had a PR after one course, but was unable to receive further chemotherapy due to toxicity. The latter pts suggest that this regimen should be studied further in pts with MDS, poor risk cytogenetics and low blast counts.

Gemcitabine plus nab-paclitaxel use in metastatic pancreatic cancer: A study of 40 patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 498-498
Author(s):  
Ivan Barrera ◽  
Sabin Dragos Filimon ◽  
Jassy Meng ◽  
Tomas Kavan ◽  
Young soo Rho ◽  
...  
Keyword(s):  
Performance Status ◽  
Real Life ◽  
Poor Performance ◽  
Poor Response ◽  
Complete Response ◽  
Primary Objective ◽  
Response To Treatment ◽  
Poor Performance Status ◽  
Dismal Prognosis ◽  
To Receive

498 Background: Metastatic pancreatic adenocarcinoma (mPDAC) carries a dismal prognosis, with often a poor response to treatment (Tx). Although gemcitabine with nab-paclitaxel (GnP) is now a standard 1st-line (1L) Tx in mPDAC, provincial policies limit its use. To understand the implications of the restriction, this real-life study was conducted. Methods: A historical prospective data was compiled using the local electronic medical record (Endovault Oncology v3.0, NY) at the Jewish General Hospital-McGill. All patients (pts) diagnosed with mPDAC that received GnP from 2013-2016 were identified. Demographics and Tx data was obtained. Primary objective was to evaluate tolerability in all lines of Tx [grade >2 CTCAE v4.03, mean Tx delay (mTxd)]. Secondary objectives were Tx attrition and outcomes [RECIST 1.1, complete response (CR), stable disease (SD) and progression disease (PD)]. Results: Of the 40 pts (female 60%, median age 64.3), 25 (62.5%) had primary at the head of the pancreas and 30 (75%) liver metastasis. 1L Tx: GnP 24 (60%), FOLFIRINOX 10 (FFX, 25%), Gemcitabine 5 (Gc, 12.5%) and FOLFOX 1 (2.5%). 70% of both FFX and Gc pts had grade 2 peripheral neuropathy (PN), neutropenia (NEUT) and fatigue. Half GnP pts had grade 2 NEUT and fatigue. mTxd in GnP, FFX and Gc were 7, 14 and 7 days. All FFX and Gc pts had PD. GnP cohort had 1 CR and 7 SD. 2L Tx was in 22 (55%): GnP 13 (59.5%), FFX 3 (13.5%), Capecitabine 2 (9%), FOLFOX 2 (9%) and Gc (9%). FFX pts 66.6% had grade 3 fatigue. GnP pts had grade 2 NEUT, PN and fatigue in 53.8%, 15.3% and 46.2%. mTxd were GnP 14 days and FFX 14 days. Except 1 SD, all FFX pts had PD. GnP pts had 1 CR, 6 SD, and 6 PD. All pts on Capecitabine, FOLFOX and Gc had PD. 3L Tx was in 6 (15%): 3 GnP (50%) and 3 on clinical trials (50%). All pts had PD and < 3 cycles. In 1L FFX pts, 7/10 and 3/6 went on to receive GnP in 2L and 3L. All 1L Gc pts had 2L GnP. Only 3 pts and 1 pt from 1L GnP pts went on to receive 2L and 3L Tx. Conclusions: Due to access limitations to GnP, its use was likely reserved for poor performance status pts. Instead, 1L FFX was used when possible. 1L FFX pts received more Tx lines due to initial pt selection. Further studies are needed in broader populations to evaluate optimal 1L Tx selection accounting for expected attrition and overall survival.

Death In Complete Remission Among Patients with Acute Myeloid Leukemia: A Preventable Problem?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2710-2710
Author(s):  
Gloria Mattiuzzi ◽  
Hagop Kantarjian ◽  
Farhad Ravandi ◽  
Guillermo Garcia-Manero ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
High Risk ◽  
Causes Of Death ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Newly Diagnosed ◽  
History Of ◽  
Prior Malignancy

Abstract Abstract 2710 Background: Significant advances in the treatment of patients with acute myelogenous leukemia (AML) and high risk myelodysplastic syndrome (HR-MDS) have improved their outcome. Mortality among patients with newly diagnosed AML and HR-MDS is mainly attributed to persistent disease (i.e., failure to achieve or loss of complete remission [CR]), infectious and other complications during induction chemotherapy. However, a small but significant proportion of patients die in CR. The aim of this study was to investigate the cause of death in AML and HR-MDS patients in CR and to analyze the associated risk factors. Methods: Retrospective review of medical records of patients with newly diagnosed AML, APL and HR-MDS who received induction chemotherapy at the Department of Leukemia at MD Anderson from January 2000 to December 2009. Results: During the study period, 2156 patients were treated. One thousand one hundred fifty patients achieved CR for an overall CR rate of 53%. Among them, 114 patients (10%) died in CR. The median time from achievement of CR to death was 5.3 months (range, 0.2 – 79). There was a decline in the rate of death in CR over the 10 years of analysis reported (p=0.010). [Table 1] Information about the causes of death in 35 patients (31%) was not available. The most frequent causes of death in the remaining 79 patients were infections (27%); SCT-related complications (19%); relapse of prior malignancy (8%); hemorrhage (4%); multi-organ failure (4%); and others (9%). Among patients who died in CR, 105 (92%) had AML and 9 high-risk MDS, 60% were female, and the median age was 64 years (range 21–86). Forty-two patients (37%) had history of a prior malignancy, 22% had received previous chemotherapy (for other malignancies), and 20% prior radiotherapy. Sixty-eight percent received high-dose cytarabine-containing regimen for induction therapy, 92% achieved CR after one cycle of chemotherapy, with a median of 33 days (range 21–152) to achievement of CR. Nineteen percent underwent stem cell transplantation while in CR. In comparison to patients who did not die in CR, patients who died in remission were significantly older at the time of diagnosis [64 vs. 57 years, p <.001]; were more likely to have history of prior malignancy, chemotherapy or radiotherapy [37% vs.21%, p<0.001; 22% vs.11%, p<0.001; 20% vs. 9%, p<0.001, respectively]; had worse performance status at the time of diagnosis [26% vs. 14%, p = 0.004]; and were more likely to have undergone stem cell transplantation (SCT) while in CR [19% vs. 8%, p<0.001]. Sixty-three percent of the patients who died in CR were 60 years or older. Among patients age 60 years or older, the probability of death in CR was 14% compared to 7% for patients younger than 60 (p<0.001). Multivariate logistic regression analysis confirmed that older age (p<0.000), prior malignancy (p<0.001), poor performance status (p<0.001) and SCT while in CR (p<0.000) were independently associated with the probability of dying in CR. Risk factors for dying from infections included only older age (p<0.003) and poor performance status (p, 0.05). Conclusion: Death in CR affects a significant number of patients with AML, with older patients with poor performance status having the highest probability of dying in CR, particularly from infections. Special attention should be put to these patients to minimize their risk of death in CR to improve their long term outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk Factors for Overall Survival in Children with High Risk Acute Myeloid Leukemia (HR AML) after Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity of Conditioning Regimens

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Elena Vladimirovna Semenova ◽  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Hematopoietic Stem ◽  
Factors Influencing ◽  
Remission Status ◽  
Conditioning Regimens ◽  
The Moment

Background: Traditionally, children with AML undergo аllo-HSCT with myeloablative conditioning (MAC). It is known that MAC is associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities. But there is no conclusive evidence to support efficacy of RIC allo-HSCT in children suffering from different malignant diseases including AML. The aim: To compare efficacy of different intensity conditioning regimens in children with high risk (HR) AML (according to AML-BFM protocols 1998 and 2004) and to identify factors which have a prognostic significance for overall survival (OS). Patients and methods: Retrospective analysis was performed in 192 patients (pts) with AML (median age of 10 years (0.5-18 y.o.), who received allo-HSCT at R.M. Gorbacheva Research Institute between 08/2000 and 09/2019. MAC (busulfan- or treosulfan-based) were used in 109 pts: 1st CR - 46 pts (MRD+ n=11), 2nd CR - 18 pts, 3rd CR - 1 pt, relapse - 44 pts. Allo-HSCT with RIC were performed in 83 pts: 1st CR - 32 pts (MRD+ n=13), 2nd CR -19 pts, 3rd CR - 4 pts, relapse -28 pts (p=0,674). RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melphalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). Indication for RIC allo-HSCT was poor performance status (Lansky/Karnofsky score ≤70%), or organ dysfunction due to previous therapy, or infectious complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 30 pts (16%), from matched unrelated donor - in 98 pts (51%), haploidentical - in 64 pts (33%) and the donor distribution was not different between groups (p=0,878). Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (53%). OS were estimated using Kaplan-Meier curves. Univariate analyses were performed using the log rank test for OS, Grey test for cumulative incidences. Multivariate analyses were performed using the Cox proportional-hazard model. Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment &gt;=0,5x109/l was D+16 (range D+8-52). Engraftment was observed in 67 pts (81%) after RIC and 94 pts (86%) after MAC (p=0,231). OS after RIC allo-HSCT in the 1st CR was 76% and after MAC - 68% (p=0,014), in 2nd CR 50% after RIC and 54% after MAC (p=0,058), in advanced disease 14% after RIC and 16% after MAC (p=0,394). The transplant-related mortality rate was 19% after RIC and 22% after MAC (p=0,546). Risk of relapse was 28% after RIC and 26% after MAC (p=0,456). Factors influencing OS after MAC were: 1) Remission status at the moment of allo-HSCT (р=0.001); 2) Presence of aGVHD grade I-II (р=0,005); 3) Relapse or MRD+ status after allo-HSCT (р=0.012); 4) Lansky score &gt;70% (р=0,024). Factors influencing OS after RIC were: 1) Remission status at the moment of allo-HSCT (1st remission) (p=0,001); 2) Lansky score &gt;70% (р=0,004). Conclusion: The effectiveness of RIC and MAC is comparable in children with HR AML, but RIC demonstrated better results in 1st CR. The presence of I-II grade aGVHD had positive effect in MAC. Factors influencing OS in both groups were disease status at the moment of allo-HSCT and performance status before allo-HSCT The use of RIC can be effective in patients, especially those who have undergone allo-HSCT in the 1st remission, while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Multicenter studies are warranted, especially for patients in the first CR, where long-term complications are of most importance. Disclosures No relevant conflicts of interest to declare.

What can we do for gastrointestinal cancer patients with poor performance status (PS)?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19629-19629
Author(s):  
K. Shitara ◽  
M. Munakata ◽  
O. Muto ◽  
M. Kasai ◽  
Y. Sakata
Keyword(s):  
Cancer Patients ◽  
Tumor Markers ◽  
Gastrointestinal Cancer ◽  
Survival Benefit ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Ecog Ps ◽  
To Receive ◽  
Measurable Lesion

19629 Background: The prognosis of advanced gastrointestinal cancer patients, especially those with poor PS, is generally dismal. Needless to say, such patients are ineligible for participation in clinical studies. However, there are many patients with poor PS who wish to receive chemotherapy. Methods: From June 2000 to October 2006, a total of 508 patients with advanced cancer, including 304 gastrointestinal cancer patients, were treated by chemotherapy in our hospital. Of these, 110 gastrointestinal cancer patients (gastric=35, colorectal=30, pancreatic=26, biliary tract=11, esophageal=8) had poor PS (ECOG PS 3 = 68 patients, PS 4 = 42 patients). In 103 patients with at least one measurable lesion, a partial response according to RECIST criteria was obtained in 13 patients (12.6%). In 60 patients with ascites (47 patients), pleural effusion (25 patients), or both (12 patients), 11 of the patients (18.3%) achieved decreased fluid accumulation. A decline in tumor markers (>25%) was observed in 28 patients. Improvement in PS was seen in 13 patients (11.8%). As a result, 35 patients (31.8 %, including 9 patients with PS 4) achieved a tumor response, a decrease in accumulated fluid, or a decline in tumor markers, which resulted in a survival benefit compared to the other 75 patients without effect (6.4 months vs. 2.3 months, p<0.001). Alleviation of some symptoms was observed in 28 out of 98 symptomatic patients (30.4%). A better response and/or a decline in tumor markers significantly correlated with alleviation of symptoms (p<0.001). No treatment related death was seen. Conclusions: With regard to response rate, chemotherapy was rarely effective for patients with advanced gastrointestinal cancer with poor PS. However, more than a few patients gained a certain survival benefit and alleviation of symptoms. Thus, chemotherapy may be warranted in cases of patients with advanced gastrointestinal cancer who wish to receive chemotherapy despite the low possibility of response. No significant financial relationships to disclose.

Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 534-534
Author(s):  
Hui-li Wong ◽  
Kathryn M Field ◽  
Jeanne Tie ◽  
Suzanne Kosmider ◽  
Jeremy David Shapiro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Clinical Care ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Routine Practice ◽  
Ecog Ps ◽  
To Receive

534 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centres. Results: Of the 679 patients entered, 129 (19.0%) had an ECOG PS ≥ 2. In total, 77 (11.3%) were PS 2, 41 (6.0%) PS 3 and 11 (1.6%) PS 4. Chemotherapy was administered to 55 (71.4%) PS 2 and 15 (36.6%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (55.0% versus 86.8%, p<0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (38.0% vs 71.6%, p<0.0001) or bevacizumab (15.5% vs 46.9%, p<0.0001). Overall survival (OS) was reduced with declining PS, with medians of 31.2, 9.0, 3.0 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p<0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.8 vs 4.1 months for untreated patients, p<0.0001). At one and two years, 22 (31.4%) and 8 (11.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.

Outcome of trimodality-eligible esophagogastric cancer (EC) patients who declined surgery after preoperative chemoradiation.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Takashi Taketa ◽  
Arlene M Correa ◽  
Akihiro Suzuki ◽  
Mariela Anabel Blum ◽  
Jeffrey Edwin Lee ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Performance Status ◽  
Preoperative Staging ◽  
Poor Performance ◽  
Complete Response ◽  
Endoscopic Biopsy ◽  
Preoperative Chemoradiation ◽  
Poor Performance Status ◽  
Trimodality Therapy ◽  
Esophagogastric Cancer

6 Background: Patients with localized EC eligible for resection at presentation should receive trimodality therapy (chemoradiation and surgery). However, surgical resection is not always performed in these patients because of poor performance status or reluctance in eligible patients to proceed with surgical resection after preoperative chemoradiation. Reports on the outcome of such patients are rare. Methods: Between 2002 and 2010, we identified 599 trimodality-eligible EC patients in our prospective database. All patients had extensive baseline staging, preoperative chemoradiation, and preoperative staging that included endoscopic biopsy and PET-CT. Of 599 patients, 32 patients declined surgery. Results: The median age was 70 years (range, 55-81), 29 patients (90.6%) were men and 30 (93.8%) were Caucasian. Majority had baseline stage II (44%) or III (38%) cancer. All 32 patients had an adenocarcinoma (moderate: 53.1%, poorly: 46.9%) and reached a clinical complete response (negative biopsy and PET in the physiologic range) post-chemoradiation. Four patients had salvage surgery and 3 are alive. Overall, 22 patients remain alive at a median follow up of 33.1 months (95% CI, 28.1-38.1). 3-year overall survival (OS) and relapse-free survival (RFS) were 65.1±10.4% and 37.5±10.3%. Median OS and RFS were 54.2 months (95% CI, 25.7-82.7), 30.4 months (95% CI, 16.3-44.5). Conclusions: Although the outcome of patients with EC who decline surgical resection after chemoradiation is reasonable, the lack of a validated approach to esophageal preservation dictates that trimodality therapy remains the standard of care in patients with potentially resectable EC.

Is there a role for chemotherapy in metastatic colorectal cancer patients with a poor performance status?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14583-e14583
Author(s):  
Hui-li Wong ◽  
Kathryn M Field ◽  
Jeanne Tie ◽  
Suzanne Kosmider ◽  
Jeremy David Shapiro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Clinical Care ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Routine Practice ◽  
Ecog Ps ◽  
To Receive

e14583 Background: The management of patients with poor performance status (PS) remains challenging in the absence of data on optimal treatment. Here we assessed the treatment and outcomes of patients with metastatic colorectal cancer (mCRC) with poor Eastern Cooperative Oncology Group (ECOG) PS (≥ 2) in routine clinical care. Methods: Analysis of patients prospectively entered onto the TRACC (Treatment of Recurrent and Advanced Colorectal Cancer) database, a clinician-designed initiative to collect comprehensive data on consecutive patients with mCRC from sites across Australia. Data collection commenced in July 2009 and is ongoing at 14 participating public and private centers. Results: Of the 864 patients entered, 161 (18.6%) had an ECOG PS ≥ 2. In total, 95 (11.0%) were PS 2, 54 (6.3%) PS 3 and 12 (1.4%) PS 4. Chemotherapy was administered to 65 (68.4%) PS 2 and 17 (31.5%) PS 3 patients, with none of the PS 4 patients being treated. Overall, poor PS patients were significantly less likely to receive any chemotherapy compared to their good PS (PS 0-1) counterparts (51.6% versus 86.8%, p<0.0001) and, when chemotherapy was given, significantly less likely to receive combination chemotherapy (67.5% vs 81.1%, p=0.0057) or bevacizumab (31.3% vs 55.8%, p<0.0001). Overall survival (OS) was reduced with declining PS, with medians of 28.7, 8.9, 3.5 and 0.8 months for PS 0-1, 2, 3 and 4 patients respectively (p<0.0001). Poor PS patients treated with chemotherapy had a better OS outcome (9.0 vs 3.5 months for untreated patients, p<0.0001). At one and two years, 24 (28.9%) and 7 (8.4%) treated poor PS patients were alive. Conclusions: In routine practice many patients with a poor PS, particularly those that are PS 2, receive active treatment. Although overall survival for poor PS patients is poor, some patients appear to benefit from treatment. Further data analysis, particularly to define subsets that may benefit most from treatment, is planned as further sites around Australia contribute data to the project.

scholarly journals “IDENTIFYING HIGH-RISK CHRONIC LYMPHOCYTIC LEUKEMIA: A PATHOGENESIS-ORIENTED APPRAISAL OF PROGNOSTIC AND PREDICTIVE FACTORS IN PATIENTS TREATED WITH CHEMOTHERAPY WITH OR WITHOUT IMMUNOTHERAPY.”

2016 ◽  
Vol 8 ◽  
pp. 2016047 ◽  
Author(s):  
Sara Martinelli ◽  
Antonio Cuneo ◽  
Gian Matteo Rigolin
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Poor Performance ◽  
High Serum ◽  
Lymphocytic Leukemia ◽  
Response To Treatment ◽  
Poor Performance Status

 Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical behaviour. Accurate prognostication and prediction of response to treatment is important in an era of effective first-line regimens and novel molecules for high risk patients. Because a plethora of prognostic biomarkers were identified, but few of them were validated by multivariable analysis in comprehensive prospective studies, we applied in this survey stringent criteria to select papers from the literature in order to identify the most reproducible prognostic/predictive markers. Each biomarker was analysed in terms of reproducibility across the different studies with respect to its impact on time to first treatment (TTFT), progression free survival (PFS), overall survival (OS), response to treatment and transformation into Richter’s syndrome (RS). We were able to identify the following biomarkers as the most reliable in guiding risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV unmutated configuration, short telomeres and 11q-. However, the method for measuring telomere length was not validated yet and 11q- was predictive of inferior OS only in those patients who did not receive FCR-like combinations. Stage and lymphocytosis were predictive of shorter TTFT and age, high serum thymidine kinase levels and poor performance status were predictive of shorter OS. Using our stringent criteria no parameter was found to independently predict for inferior response to treatment or development of RS.  

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity Conditioning Regimens in Children with Very High Risk Acute Lymphoblastic Leukemia (VHR ALL): A Single-Center Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2050-2050
Author(s):  
Elena Vladimirovna Semenova ◽  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
...  
Keyword(s):  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Very High ◽  
Reduced Intensity

Background: Allo-HSCT with myeloablative conditioning (MAC) has traditionally been performed in patients with ALL and has been associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities or in elderly patients. In contrast to the adults, the RIC pediatric experience is still sparse. The aim: to compare efficacy of reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) for allo-HSCT in children suffering from very high risk (VHR) ALL. Patients and methods: This was a retrospective analysis performed in 233 patients (pts) with ALL (age - from 4 month till 18 y.o. (mediana 11 y.o.)), who received allo-HSCT at R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation between 12/2000 and 12/2017. MAC (busulfan or treosulphan containing) was used in 159 pts: 1st CR - 26 pts, 2nd CR -57 pts, 3rd or 4th CR 23 - pts, relapse -53 pts. Allo-HSCT with RIC was performed in 74 pts: 1st CR - 14 pts, 2nd CR -29 pts, 3rd or 4th CR - 12 pts, relapse -20 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melfalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). The disease status was not different between groups (p=0.674) Indication for RIC allo-HSCT was poor performance status (Lanskoy/Karnovsky<70%), organ dysfunction due to previous therapy or infectioous complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 41 pts, from matched unrelated donor - in 131 pts, haploidentical - in 61 pts. Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (44%). Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment >=0,5x109/l was D+18 (range D+8-48). Transplant engraftment was observed in 64 pts (86%) after RIC and 150 pts (93%) after MAC (p=0,224). OS pts after RIC allo-HSCT performed in 1 CR 70% and after MAC - 85% (p=0,043), in 2 CR 56% after RIC and 49% after MAC (p=0,436), in 3 or 4 CR 34% after RIC and 25% after MAC (p=0,394). OS in patients with active disease was 16% in RIC-group and 18% in MAC-group (p=0,432). The transplant-related mortality rate was 18% after RIC and 20% after MAC (p=0,40). Risk of relapse was 37% after RIC and 42% after MAC (p=0,39). Acute GVHD II-IVgr developed in 32% pts after RIC and 33% after MAC (p=0,883), early infections were diagnosed in 63% in RIC-group, and 59% in MAC-group (p=0,356). Early toxic complications were observed (CTC): mucositis III-IV gr in 13% pts after RIC and in 54% pts after MAC (p=0,001), nephrotoxicity in 7% pts and in 21% pts (p=0,042), hepatitis gr II-III in 24% pts and in 57% pts, respectively (p=0,034), neurological complications in 22% pts and 42% pts, resp. (p=0,046). Conclusion: RIC allo-HSCT of VHR ALL in 2,3 or 4 CR pts ≤ 18 y.o. is effective and comparable with MAC allo-HSCT. Early toxic complications after RIC were less frequent. Possibly, the use of RIC can maintain efficacy while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Disclosures Moiseev: Pfizer: Other: Travel grants; BMS: Other: Travel grants; MSD: Other: Travel grants; Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; Celgene: Consultancy, Other: Travel grants; Takeda: Other: Travel grants.

scholarly journals Disease Characteristics, Patterns of Care, and Survival in Very Elderly Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4480-4480
Author(s):  
Jessica N. Williams ◽  
Ashish Rai ◽  
Joseph Lipscomb ◽  
Jean L. Koff ◽  
Loretta J. Nastoupil ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Poor Performance Status ◽  
Very Elderly ◽  
Selection Factors ◽  
The Impact ◽  
To Receive

Abstract Context: Despite having the highest incidence of diffuse large B-cell lymphoma (DLBCL), individuals older than 80 years are rarely included in DLBCL clinical trials or epidemiological studies. We sought to better characterize DLBCL presentation, treatment, and survival patterns for this age group. Objective: We investigated demographic and clinical characteristics at diagnosis, treatment selection factors, and the impact of treatment regimen on overall survival (OS) and lymphoma-related survival (LRS) for DLBCL patients >80 years. We hypothesized that patients >80 years were more likely to undergo observation and less likely to receive standard-of-care rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We also hypothesized that patients >80 years who received R-CHOP would have superior OS and LRS, even after controlling for demographic and clinical factors. Methods: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to examine DLBCL patients diagnosed from 1999-2009 and followed through 2010. Our population-based cohort contained 5,924 DLBCL patients aged ≥66 years; 1,422 were >80 years. Only patients treated within 6 months of diagnosis with R-CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); cyclophosphamide, vincristine, and prednisone (CVP); rituximab plus CVP (R-CVP); or patients undergoing observation were included in order to examine factors associated with the use of anthracyclines. Chi-squared tests compared characteristics and initial treatments of DLBCL patients >80 years and 66-80 years. Multivariable logistic regression models examined treatment selection factors in patients >80 years. Standard and propensity score-adjusted multivariable Cox proportional hazards models adjusted for patient demographics, clinical characteristics, comorbidities, performance status, and year of diagnosis examined relationships between treatment regimen, treatment duration, and survival. Results: Among patients >80 years, 58% were female, 91% were Caucasian, 36% had stage III/IV disease, 39% had extranodal involvement, 7% had B-symptoms, 28% had poor performance status, and 14% had ≥2 comorbidities. Patients >80 years were less likely to receive R-CHOP (43% vs. 61%) and more likely to be observed (30% vs. 15%) or receive R-CVP (12% vs. 4%); all p<0.0001. Sex, marital status, area-level poverty, year of diagnosis, performance status, and disease site were associated with R-CHOP treatment in patients >80 years. The initial receipt of R-CHOP was more commonly associated with female sex (odds ratio (OR) 1.31, 95% confidence interval 1.01-1.71), being married (OR 1.69, 1.07-2.66) and a diagnosis after 2001 (OR for 2002 11.71, 6.32-21.70; persistently increased ORs thereafter). The initial receipt of R-CHOP was less commonly associated with extranodal disease (OR 0.71, 0.55-0.91), poor performance status (OR 0.57, 0.44-0.75), and residence in a census tract with >12% of residents living in poverty (OR 0.69, 0.50-0.96). Initial observation was more commonly associated with the same factors that were less commonly associated with R-CHOP use and was less commonly associated with stage III/IV disease (OR 0.66, 0.50-0.87). Kaplan-Meier survival curves revealed that in patients >80 years, R-CHOP was associated with the best OS and LRS. Multivariable Cox proportional hazards models revealed that R-CHOP for >4 cycles was associated with the best OS in patients >80 years of all stages (hazard ratio (HR) 0.48, 0.37-0.62). Among stage III/IV patients, R-CHOP for >4 cycles (HR 0.48, 0.31-0.72) and R-CVP for >4 cycles (HR 0.40, 0.21-0.76) demonstrated significantly longer OS. Conclusions:Although DLBCL patients >80 years were less likely to receive R-CHOP, this regimen conferred the best survival. The failure of very elderly DLBCL patients to receive R-CHOP may occur due to clinical factors such as poor performance status, but commonly varies across demographic factors such as area-level poverty, which may reflect bias in the under-utilization of R-CHOP in very elderly patients that is not based on clinical parameters. Further studies are needed to characterize the impact of DLBCL treatment on quality of life in very elderly patients, and algorithms should be developed to help guide therapy in this population. Disclosures No relevant conflicts of interest to declare.

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