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

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 >=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 >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 >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.

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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 ◽

10.1182/blood-2019-128163 ◽

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.

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

Blood ◽

10.1182/blood.v104.11.4723.4723 ◽

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.

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Alkylator-Based Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) in Lymphoma: A Registry Study Comparing Thiotepa-, Busulfan-, Melphalan- and Treosulfan-Containing Regimens On Behalf of the EBMT Lymphoma Working Party

Blood ◽

10.1182/blood.v120.21.2033.2033 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2033-2033

Author(s):

Peter Dreger ◽

Herve Finel ◽

Renato Fanin ◽

Paolo Corradini ◽

Michele Falda ◽

...

Keyword(s):

Cell Lymphoma ◽

Performance Status ◽

Conditioning Regimen ◽

Working Party ◽

B Cell Lymphoma ◽

Poor Performance Status ◽

Unrelated Donor ◽

Hematopoietic Stem ◽

Remission Status ◽

Significant Difference

Abstract Abstract 2033 Background: Thiotepa (TT) is an alkylating agent approved for conditioning for alloHSCT. TT-based alloHSCT has been pioneered in a variety of lymphoma subtypes with promising results, but the available information about the value of thiotepa in this indication compared to other alkylator-based regimens is still limited. Primary objective was to compare the outcome of TT-based alloHSCT with that of alloHSCT conditioned with other alkylator regimens (non-TT) separately for diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and peripheral T Cell lymphoma (PTCL). Primary endpoint was event-free survival (EFS); secondary endpoints were overall survival, non-relapse mortality (NRM), and relapse incidence. Eligible were patients >18 years who had received TT-, busulfan (BU)-, melphalan- (MEL), or treosulfan- (TREO) based conditioning for T-replete alloHSCT between 2003–2010 for FL, DLBCL, or PTCL. Statistical analysis was based on multivariable comparisons using stratified Cox and Fine & Gray regression models. Results: 201 patients with TT fulfilled the inclusion criteria and were compared with 578 non-TT patients (BU 55%, MEL 35%, TREO 10%). The most frequently used specific regimens were TT-cyclophosphamide combinations (75%) in the TT group and BU-fludarabine combinations (52%) in the non-TT group. Of the total 779 patients, 43%% had FL, 39% DLBCL, and 18% PTCL. TT and non-TT patients were comparable for age, sex, time from diagnosis, remission status at HSCT, and proportion of unrelated donor transplants. However, the TT group contained significantly more patients with PTCL (24% vs 15%), with poor performance status (PS; 12.5% vs 3%), and with BM as HSCT source (14% vs 9%). By multivariate comparisons considering conditioning, age, sex, remission status, PS, and time from diagnosis, EFS was significantly affected by active disease at HSCT and poor PS in all three lymphoma subtypes. In contrast, conditioning with TT had no significant impact (Hazard ratio (HR) 1.06 (0.67–1.67) for FL; 1.01 (0.67–1.51) for DLBCL; 1.33 (0.75–2.36 for PTCL) on EFS or any other endpoint. Similar results were seen when the analysis was broken down to specific conditioning regimens (TT-CY vs BU-based). MEL- and TREO-based regimens did not show a significant difference compared to BU for any endpoint. Conclusions: This study failed to identify significant outcome differences between the four conditioning regimen types tested. However, the limitations inherent to registry analyses have to be considered. In particular, conclusions on differential regimen toxicity apart from NRM will require additional, ideally prospective studies. Disclosures: Dreger: Riemser G, Greifswald, Germany: Consultancy, Honoraria, Research Funding. Off Label Use: Treosulfan for conditioning for allogeneic HSCT. Schmitz:Riemser AG, Greifswald, Germany: Honoraria.

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Gemcitabine (GEM) (day 1–8) plus carboplatin (CBDCA) (day 2) for the treatment of advanced non-small cell lung cancer (aNSCLC) in elderly or poor performance status (PS) patients (pts)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18116 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18116-18116

Author(s):

F. Sperandi ◽

B. Melotti ◽

A. A. Martoni

Keyword(s):

Overall Survival ◽

Performance Status ◽

Objective Response ◽

Haematological Toxicity ◽

Dose Intensity ◽

Poor Performance ◽

Primary Objective ◽

Hematological Toxicity ◽

Poor Performance Status ◽

Histologic Subtype

18116 Background: Several studies have demonstrated that the combination of CBDCA plus GEM according to various regimens appears as effective as cisplatin (CP) containing regimens. CBDCA plus GEM regimens are associated with more haematological toxicity (G3–4 leucopenia 17–40.6%, G3–4 neutropenia 29–75%, G3–4 thrombocytopenia 21–57% and G3–4 anaemia 5–33%), but with lower non-hematological toxicity as compared to CP-based regimens. Methods: The primary objective of this trial was the evaluation of the overall survival, while the secondary objectives were assessment of objective response and toxicity in elderly or poor PS pts. The eligible pts had previously untreated aNSCLC not suitable for CP-based chemotherapy. Pts received each at 3-week intervals GEM 1000 mg/sq on day 1 and 8 plus CBDCA area under the curve of 5 on day 2. Between April 2004 and January 2007, 54 consecutive pts were accrued in the study. Pt characteristics were: 42 (78%) males and 12 (22%) females; median age 72 years (range: 56–84 years) with 67% of pts = 70 years; median Karnofsky PS 90 (range: 50–100) with 33% of pts = 80; stage disease: IIB not suitable for surgery in 1 (2%) pt, IIIA in 5 (9%), IIIB in 10 (19%), IV in 33 (61%) and recurrent disease in 5 (9%); histologic subtype: adenocarcinoma in 30 (56%) pts, epidermoid in 11 (20%), bronchioalveolar carcinoma in 2 (4%) and other histologic subtypes in 11 (20%). Results: A median of 4 courses was administered (range 1–8). Dose- intensity was 98.7% (range 50–100%) for CBDCA and 87.2% (range 60–100%) for GEM. Objective response according to intention-to-treat analysis was as follows: 15 (28%) pts had PR, 16 (29%) had SD, 14 (27%) had PD and 9 (16%) were not assessable because lost to follow-up or too early. Median overall survival was 10 months. WHO G3 leucopenia was observed in 5 (9%) pts, G3–4 neutropenia in 15 (28%), G3 thrombocytopenia in 7 (13%) and G3 anaemia in 2 (4%). No WHO G3–4 non-hematological toxicity was observed. Conclusions: This regimen is feasible and active in elderly or poor PS pts. It can be administered in a outpatient setting because toxicity is moderate and manageable. No significant financial relationships to disclose.

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.534 ◽

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.

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Palliative inpatient chemotherapy: Clinical benefit or harm?

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e19527 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e19527-e19527 ◽

Cited By ~ 1

Author(s):

Maria Ali ◽

M. Christine Cripps ◽

Katelyn Balchin ◽

Jennifer Spencer ◽

Paul Wheatley-Price

Keyword(s):

Overall Survival ◽

Clinical Benefit ◽

Performance Status ◽

Retrospective Chart Review ◽

Poor Performance ◽

Hospitalized Patients ◽

Poor Performance Status ◽

Advanced Cancer Patients ◽

Cancer Symptoms ◽

Ottawa Hospital

e19527 Background: Palliative chemotherapy (CT) is given with the goals of palliating cancer symptoms and prolonging life. Patients with a poor performance status (PS) generally derive less benefit from CT and may experience greater toxicity. Advanced cancer patients admitted to hospital generally have a poor PS, and yet palliative CT is often administered to hospitalized patients. The evidence to support palliative CT in hospitalized patients is scarce. We hypothesize that palliative in-patient CT does not result in meaningful clinical benefit. Methods: With ethics approval, a retrospective chart review was undertaken to report outcomes from in-patient CT at the Ottawa Hospital Cancer Centre between April 2008- January 2010. From hospital pharmacy records, all advanced solid tumor patients receiving in-patient palliative CT were identified. Patients receiving radical, curative, neo- or adjuvant therapy, or those admitted for an inpatient regimen, were excluded. The primary endpoints were overall survival following CT, place of discharge from hospital, and whether further CT was received. Results: We report 199 in-patients (23% breast cancer, 22% small cell lung cancer, 16% NSCLC, 39% other) who received CT (median 1 cycle, range 1-5) during the study period. The median age was 61 (range 19-88); 59% were female. The main reasons for hospital admission were dyspnea (31%) or pain (29%). At baseline 25% were anemic, 36% had leucocytosis and 70% were hypoalbuminemic (<30g/l). 67% were receiving 1st line CT. The median overall survival was 4.5 months (95% CI: 3.2 - 5.8). Longest survival was seen in SCLC patients (7.3m). 77% of patients were discharged home, but 17% died during the admission. 72% of patients received further systemic therapy. Factors significantly associated with shorter survival were hypoalbuminemia (HR 1.52, 95% CI 1.06- 2.18, p=0.02), and therapy in 2nd line or beyond (HR 2.10, [1.37-3.23], p<0.001). Receiving treatment beyond 1st line, and baseline leucocytosis, were both significantly associated with patients being less likely to be discharged home or receive further CT. Conclusions: While in-patient palliative CT is associated with short survival, many patients remain well enough to be discharged home and receive further therapy.

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e14583 ◽

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.

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Prognostic factor of nivolumab for advanced gastric cancer patients with poor performance status patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.391 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 391-391

Author(s):

Toshihiko Matsumoto ◽

Ukyo Okazaki ◽

Yusuke Kurioka ◽

Shogo Kimura ◽

Takao Tsuzuki ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Prognostic Factor ◽

Advanced Gastric Cancer ◽

Performance Status ◽

Prognostic Index ◽

Poor Performance ◽

Poor Performance Status ◽

Good Group ◽

Poor Group

391 Background: Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcome compared to best supportive care in AGC patients who received at least two prior regimen. Although there is not reliable date of poor performance status(PS) AGC patients who received nivolumab. We investigated efficacy and safety of nivolumab for AGC patients with poor PS. Methods: We retrospectively collected clinicopathologic data from patients with AGC who received nivolumab monotherapy in Himeji Red Cross Hospital from October 2017 to June 2019. Results: 49 AGC patients who received nivolumab were analyzed. 27 patients were PS 0 or 1(Good Group), and 22 patients were PS 2 or 3(Poor Group). Median progression free survival and overall survival was 61 days and 180 days in Good Group and 36 days and 85 days in Poor Group. Overall survival (OS) was significantly shorter in Poor group(180 days vs 85 days, p = 0.0255). Disease control rate was 23% in Good group and 9% in Poor group. 33% patients were experienced immune related adverse event (iRAE) in Good Group, and 18% in Poor Group. We investigated prognostic factor of OS in Poor Group such as Royal Marsden Hospital Score(RMH score), modified Glasgow prognostic score(mGPS), and Japan Clinical Oncology Group (JCOG) prognostic index. RMH score and JCOG prognostic index good or moderate group was significantly longer overall survival than poor group (93 days vs 35 days (p = 0.0214)). JCOG prognostic index was most correlated with OS among these tools. Conclusions: This study suggested that nivolumab has a modest effect and is feasible as third line or later line for AGC patients. JCOG prognostic index was suggested to be effective in predicting prognosis in AGC patients who received nivolumab.

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Allogeneic HSCT for Hematologic Malignancies in 145 Patients - Identical Biologic Prognostic Factors Affect Outcome Despite Different Conditioning Regimen Intensities.

Blood ◽

10.1182/blood.v110.11.1087.1087 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1087-1087

Author(s):

Damiano Rondelli ◽

Sandeep Chunduri ◽

Lisa Dobogai ◽

Jayesh Mehta

Keyword(s):

Risk Factors ◽

Prognostic Factors ◽

Performance Status ◽

Poor Performance ◽

Hematologic Malignancies ◽

Poor Performance Status ◽

Donor Age ◽

Gvhd Prophylaxis ◽

Related Risk ◽

Conditioning Regimens

Abstract Analysis of pre-transplant variables affecting the outcome of allogeneic HSCT after 100 mg/m2 melphalan (± 50 mg/kg cyclophosphamide depending upon prior autograft) in 91 adult patients with hematologic malignancies identified refractory disease, poor performance status (ECOG 2/3), elevated LDH, and donor age >45 years as significant adverse prognostic factors affecting overall survival (OS) (Mehta et al. ASH 2006, BMT 2006). GVHD prophylaxis comprised cyclosporine-mycophenolate (HLA-matched siblings) or tacrolimus-mycophenolate (other donors). The patients were treated at NU. The outcome of 54 patients with hematologic malignancies treated at UIC with more intensive conditioning regimens was studied to see if the prognostic factors identified at NU were applicable to them. The conditioning regimens at UIC comprised 12.8 mg/kg IV busulfan + 120–160 mg/m2 fludarabine (n=36) or 140 mg/m2 melphalan + 150 mg/m2 fludarabine (n=18). Tacrolimus and methotrexate were used for GVHD prophylaxis. While the characteristics of the two patient populations were significantly different (especially diagnosis), transplant-related mortality and relapse rates were not significantly different for the two centers. As the table below shows, chemorefractory disease, poor performance status, and elevated LDH were adverse risk factors for OS in both groups of patients. Variable Mel100 (NU) BuFlu/Mel140 (UIC) (OS) RR (95% CI) P RR (95% CI) P *Note the disparity - unfavorable in the NU group and favorable in the UIC group Refractory disease 3.0 (1.7–5.0) 0.0001 4.5 (1.8–11.4) 0.002 Performance status 2/3 3.9 (2.2–6.8) <0.0001 6.0 (2.0–17.8) 0.001 Elevated LDH 2.1 (1.3–3.5) 0.004 4.2 (1.7–10.8) 0.003 Donor age >45 1.9 (1.2–3.2) * 0.009 0.24 (0.06–1.03) * 0.06 However, donor age >45, an adverse risk factor in the NU population, appeared to be a borderline favorable factor in the UIC population. HLA mismatch was found to be an additional significant adverse risk factor in the combined population when it did not reach statistical significance in either group individually. The figures below shows the effect of the number of adverse risk factors (excluding donor age) on DFS and OS in the entire group of 145 patients (P<0.0001 for each). We conclude that biologic disease-related risk factors such as chemorefractoriness and elevated LDH, and patient-related risk factors such as poor performance status appear to be applicable to allograft recipients irrespective of the intensity of the underlying transplant procedure. The reason for the disparate effect of donor age in the two groups of patients is unclear, and needs to be studied further. Figure Figure Figure Figure

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Risk Factors For The Development Of Severe Bacterial Infection In Patients With Multiple Myeloma During Chemotherapy With Bortezomib Containing Regimens

Blood ◽

10.1182/blood.v122.21.5370.5370 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5370-5370 ◽

Cited By ~ 1

Author(s):

Shin Young Hyun ◽

Ji Eun Jang ◽

Yundeok Kim ◽

Doh Yu Hwang ◽

Soo Jeong Kim ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Overall Survival ◽

Risk Factor ◽

Bacterial Infection ◽

Performance Status ◽

Poor Performance ◽

Poor Performance Status ◽

Severe Bacterial Infection ◽

Early Course

Abstract Background The aim of this study is to identify risk factors associated with the development of severe bacterial infection (SBI) in patient with multiple myeloma (MM) during treatment with bortezomib-containing regimens. Methods A total of 98 patients with MM who were treated with bortezomib-based treatment between 2006 and 2012 were analyzed. Fifty three patients received bortezomib-dexamethasone, 25 patients received bortezomib-melphalan-prednisolone, 15 patients received bortezomib-doxorubicin-dexamethasone and 5 patients received other regimens. They received a total of 427 courses of treatment. The SBI was defined as at least grade 3 neutropenic/non-neutropenic infection by NCI Common Terminology Criteria for Adverse Events version 4.0. Using the logistic regression method, we analyzed risk factors for the development of SBI during each course of treatment. Results Median age of the patients was 62 years and 40.6% (30/98) of patients treated with bortezomib-containing regimens as first-line therapy. The SBI was developed in 57% (56/98) of patients and 19% (81/427) of bortezomib courses. Among 81 episodes of SBI, 42 (53%) episodes were clinically documented infection, 30 (37%) were microbiologically documented infections, and 9 (11%) were fever of unknown origin. The most common type of infection was pneumonia (60%). Poor performance status (ECOG ≥2) (Hazard Ratio [HR] 5.365, 95% Confidence Interval [CI] 2.004-14.364, P =.001) was the only risk factor for the development of SBI in 98 patients. When we analyzed the risk factors for the development of SBI which occurred during each treatment course, poor performance status (ECOG ≥2) (P <.001), early course of treatment (≤2 courses) (P <.001) and pretreatment lymphopenia (absolute lymphocyte count <1.0 x 109/L) (P = .043) were associated with increased risk for developing SBI in each course. These 3 risk factors remained independently significant in multivariate analysis: poor performance status (ECOG ≥2) (HR 3.920, 95% CI 2.305-6.666, P <.001), early course of treatment (≤2 courses) (HR 2.782, 95% CI 1.633-4.740, P <.001) and pretreatment lymphopenia (HR 1.728, 95% CI 1.016-2.937, P = .043). The probability of developing SBI in each treatment course was 5.1% in courses with no risk factor, 14.9% in 1 risk factor, 23.9% in 2 risk factors and 59.5% in 3 risk factors (P <.001, Figure 1). After treatment with bortezomib-containing regimens, patients who experienced SBI showed a significantly shorter overall survival than patients who didn't experienced SBI (median 6.1 month vs. 30.1 months, P = .004) although progression free survival was not different (median 18.1 months vs. 21.9 months, P = .418). The multivariate cox analysis demonstrated that the development of SBI was associated with inferior overall survival (HR 2.440, 95% CI 1.305-4.561, P = .005) as well as male sex (HR 2.323, 95% CI 1.236-4.367, P = .009). Conclusions In conclusion, we identified that poor performance status, early courses of treatment, and lymphopenia at the beginning of each treatment course were the risk factors for the development of SBI in patients with MM during treatment with bortezomib-containing regimens. Close monitoring for the development of SBI and appropriate treatment should be considered in the patients with risk factors. Disclosures: No relevant conflicts of interest to declare.

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