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 ◽  
...  

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.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4723-4723
Author(s):  
Peter Kang ◽  
Karen Seiter ◽  
Delong Liu ◽  
Muhammad Arshad ◽  
Anila Qureshi ◽  
...  

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 &lt; 8 gm/dl, platelet &lt; 50,000/mm3, neutrophils &lt; 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.


2021 ◽  
pp. 019459982110491
Author(s):  
Hiroaki Masuda ◽  
Rumi Ueha ◽  
Taku Sato ◽  
Takao Goto ◽  
Misaki Koyama ◽  
...  

Objective We examined the influence of liquid thickness levels on the frequency of liquid penetration-aspiration in patients with dysphagia and evaluated the clinical risk factors for penetration-aspiration and aspiration pneumonia development. Study Design A case series. Setting Single-institution academic center. Methods We reviewed medical charts from 2018 to 2019. First, we evaluated whether liquid thickness levels influence the frequency of liquid penetration-aspiration in patients with dysphagia. Penetration-aspiration occurrence in a videofluoroscopic swallowing study was defined as Penetration-Aspiration Scale (PAS) scores ≥3. Second, the association between liquid thickness level and penetration-aspiration was analyzed, and clinical risk factors were identified. Moreover, clinical risk factors for aspiration pneumonia development within 6 months were investigated. Results Of 483 patients, 159 showed penetration-aspiration. The thickening of liquids significantly decreased the incidence of penetration-aspiration ( P < .001). Clinical risk factors for penetration-aspiration were vocal fold paralysis (odds ratio [OR], 1.99), impaired laryngeal sensation (OR, 5.01), and a history of pneumonia (OR, 2.90). Twenty-three patients developed aspiration pneumonia while undertaking advised dietary changes, including liquid thickening. Significant risk factors for aspiration pneumonia development were poor performance status (OR, 1.85), PAS score ≥3 (OR, 4.03), and a history of aspiration pneumonia (OR, 7.00). Conclusion Thickening of liquids can reduce the incidence of penetration-aspiration. Vocal fold paralysis, impaired laryngeal sensation, and history of aspiration pneumonia are significant risk factors of penetration-aspiration. Poor performance status, PAS score ≥3, and history of aspiration pneumonia are significantly associated with aspiration pneumonia development following recommendations on thickening liquids. Level of Evidence 3.


Author(s):  
Alvin J. X. Lee ◽  
Karin Purshouse

AbstractThe SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT—chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care.


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 ◽  
...  

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.


Breast Care ◽  
2019 ◽  
Vol 14 (2) ◽  
pp. 93-98
Author(s):  
Hartmut Link

Chemotherapy-induced anemia (CIA) in cancer patients correlates with poor performance status and decreased quality of life. Currently recommended causal therapies are erythropoiesis-stimulating agents (epoetins), iron substitution, or a combination of both. Guidelines recommend considering red blood cell (RBC) transfusions for symptomatic anemia at a hemoglobin (Hb) level of <8 g/dl. Granulocyte colony-stimulating factor (G-CSF) is recommended if the risk of febrile neutropenia (FN) following from the chosen chemotherapy protocol is ≥20%. If a chemotherapy is planned that induces a moderate FN risk (10-20%), the individual overall FN risk should be assessed prior to each chemotherapy cycle, taking into account patient- or tumor-related risk factors. G-CSF is required when risk factors such as age ≥ 65 years, advanced disease or relevant comorbidity, or previous neutropenia complications are present. Neutropenia that required a shift in chemotherapy is also an indication for G-CSF prophylaxis in subsequent cycles, in order to maintain the planned dose intensity. The use of G-CSF improves patient survival and reduces the rate of neutropenia complications.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1888-1888
Author(s):  
Esa Jantunen ◽  
Carmen Canals ◽  
Didier Blaise ◽  
Alessandro Rambaldi ◽  
Herve Tilly ◽  
...  

Abstract Limited data is available on feasibility and efficacy of ASCT in elderly patients with NHL. Patients: In 2000–2005 15869 NHL patients with ASCT were reported to EBMT database, 3133 (20%) were ≥ 60 years. Only patients with MED-B dataset and those with either diffuse large B-cell lymphoma (DLBCL), mantle cell (MCL) or follicular lymphoma (FL) were subjected to more detailed analysis. This group included 906 elderly NHL patients (median age 63 years, range 60–75) (DLBCL, n = 463; MCL, n = 208; FL, n = 235) who were compared with 3661 patients &lt; 60 years (DLBCL, n = 2149; MCL, n = 435; FL, n = 1077) regarding outcome. Bulky disease was more common in younger patients (26% vs. 15%, p &lt; 0.001) as well as B-symptoms at diagnosis (42% vs. 36%, p = 0.02). Elderly patients had received more often at least two treatment lines before ASCT (70% vs. 59%, p&lt;0.001). The median follow-up for the surviving patients was 14 months. Results: Non-relapse mortality (NRM) was higher in patients ≥ 60 years of age: 3.8% vs.2.3% at 100 days, 6.9% vs. 3.9% at 1 year and 9.4% vs. 5.8% at 3 years (p&lt;0.001). No differences in NRM were observed between patients aged 60–64 years (n = 633) and those aged 65–69 (n = 240). A higher NRM was observed in DLBCL and MCL patients compared to FL patients (p=0.001and p=0.002, respectively). Other variables associated with a higher NRM were an elevated LDH at diagnosis (p=0.04), ≥ 2 treatment lines before ASCT (p&lt;0.001); a poor performance status at ASCT (p&lt;0.001); not being in CR1 at ASCT (chemosensitive disease vs. CR1, p=0.02; chemorefractory disease vs. CR1, p&lt;0.001) and BM as stem cell source (p=0.02). In multivariate analysis, elderly patients showed a higher NRM [RR = 1.6 (CI 1.2–2.1), p=0.001]. In patients with DLBCL, age ≥ 60 years at ASCT was associated with a trend to a higher risk of relapse or progression (p =0.07) and a worse PFS (p=0.008). PFS at 2 years was 69% vs. 79% for patients in CR1 and 52% vs. 60% for patients with sensitive disease at ASCT, respectively. In MCL, elderly patients had worse PFS (p=0.008). PFS at 2 years was 78 vs. 81% for MCL patients in CR1 and 52% vs. 67%, respectively for those patients autografted with sensitive disease. Older age was not a significant prognostic factor either for relapse rate or for PFS in patients with FL. PFS at 2 years was 69% and 81% for FL patients in CR1, and 69% and 69% for FL patients with sensitive disease, respectively. Conclusions: ASCT is feasible in selected NHL patients aged 60–69 years. The outcome is promising taking into account the generally poorer prognosis of lymphomas in elderly population.


2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 9628-9628 ◽  
Author(s):  
R. Nair ◽  
M. Shirodkar ◽  
M. Mallath ◽  
A. D’Cruz ◽  
P. Shukla ◽  
...  

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 224-224
Author(s):  
Marina Dusevic Kaymakcalan ◽  
Sherri Stuver ◽  
Christopher Sweeney ◽  
Toni K. Choueiri ◽  
Aymen Elfiky

224 Background: Cabazitaxel can offer a survival advantage in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). Febrile neutropenia (FN) has emerged as a serious complication, with a rate of 8% in the TROPIC trial (de Bono, Lancet 2010). Prophylaxis with pegfilgrastim (P) can decrease the risk of FN, although predictors of FN continue to evolve. We performed an analysis on the effect of prophylactic P use on FN and the impact of certain risk factors on FN rates. Methods: We conducted a retrospective analysis of mCRPC patients treated with cabazitaxel from June 2010 to August 2013 at Dana-Farber Cancer Institute. Patient clinical and treatment variables were extracted. Fisher’s exact test was used to evaluate the association between potential risk factors and FN. Results: A total of 89 patients were treated at our institution and included in this analysis. All patients received at least one dose of cabazitaxel and received a mean of four cycles. Five pts (5.6%) developed FN; 3 out of 70 (4.3%) receiving P and 2 out of 19 (10.5%) not receiving P (p=0.3). Of the 24 patients that started cabazitaxel at a reduced dose, none developed FN. No toxic death was reported. Among several risk factors including P use, age older than 65, pre-existing neutropenia, prior chemotherapy, pre-existing infection, poor performance status, liver and renal dysfunction, and recent surgery, only a prior history of palliative radiation had a significant association with FN (p=.002). Conclusions: The rate of FN in a large academic practice is similar to what was reported in the TROPIC trial. Prior radiation may be a risk factor for FN in cabazitaxel-treated mCRPC patients. Other factors that may help better predict the risk of FN in different groups of patients receiving cabazitaxel must be identified.


Author(s):  
Nimish A. Mohile ◽  
Hans Messersmith ◽  
Na Tosha Gatson ◽  
Andreas F. Hottinger ◽  
Andrew Lassman ◽  
...  

PURPOSE To provide guidance to clinicians regarding therapy for diffuse astrocytic and oligodendroglial tumors in adults. METHODS ASCO and the Society for Neuro-Oncology convened an Expert Panel and conducted a systematic review of the literature. RESULTS Fifty-nine randomized trials focusing on therapeutic management were identified. RECOMMENDATIONS Adults with newly diagnosed oligodendroglioma, isocitrate dehydrogenase (IDH)–mutant, 1p19q codeleted CNS WHO grade 2 and 3 should be offered radiation therapy (RT) and procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ) is a reasonable alternative for patients who may not tolerate PCV, but no high-level evidence supports upfront TMZ in this setting. People with newly diagnosed astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 2 should be offered RT with adjuvant chemotherapy (TMZ or PCV). People with astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 should be offered RT and adjuvant TMZ. People with astrocytoma, IDH-mutant, CNS WHO grade 4 may follow recommendations for either astrocytoma, IDH-mutant, 1p19q non-codeleted CNS WHO grade 3 or glioblastoma, IDH-wildtype, CNS WHO grade 4. Concurrent TMZ and RT should be offered to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 followed by 6 months of adjuvant TMZ. Alternating electric field therapy, approved by the US Food and Drug Administration, should be considered for these patients. Bevacizumab is not recommended. In situations in which the benefits of 6-week RT plus TMZ may not outweigh the harms, hypofractionated RT plus TMZ is reasonable. In patients age ≥ 60 to ≥ 70 years, with poor performance status or for whom toxicity or prognosis are concerns, best supportive care alone, RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable treatment options. Additional information is available at www.asco.org/neurooncology-guidelines .


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