Therapeutic Dilemma of Chemotherapy Dosing in Morbidly Obese Patient with AML: A Case Report and a Review of the Literature.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5534-5534
Author(s):  
Sakeer Hussain ◽  
Jonathan Glass ◽  
Oscar Ballester
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
White Male ◽  
Experimental Studies ◽  
Normal Karyotype ◽  
Induction Treatment ◽  
Morbidly Obese ◽  
High Dose ◽  
Obese Patients ◽  
Bone Marrow Analysis

Abstract Obesity is a common and increasing problem affecting the developed world. There is no consensus on a standard approach to chemotherapy dosing has been adopted in obese patients. We present a 25 year old white male with worsening fatigue, dyspnea and recurrent cellulites. Physical examination was significant for morbid obesity of 616 lb (BMI 86.4 and BSA 3.43m2). Initial laboratory values were WBC 0.870/ml (3400–9200/ml), Hb 6.5g/dL (11.5–15.4g/dl), platelet count of 35,000/mm3 (130000–400000/mm3), MCV 91 mm3 (80–100mm3). Basic metabolic and coagulation panel was normal except elevated D-dimer and LDH. Peripheral smear consistent with hypochromic normocytic RBC, occasional schistocytes, premature myeloid cells, myeloid blasts 26% with granularity of cytoplasm and a few Auer rods were evident. Bone marrow biopsy was consistent with acute myeloid leukemia. Flowcytometry was positive for CD33, CD 38 and myeloperoxidase. Lymphoid antigens were negative. Cytogenetic analysis revealed normal karyotype and negative for t (15; 17). Patient was treated with standard induction regimen with cytarabine 243mg (100mg/m2) and daunorubicin 109mg (45mg/m2). Chemotherapy dosing was done according to the adjusted body weight (BSA 2.43 m2). Day 14 bone marrow was consistent with significant disease. Reinduction with high dose cytarabine 14000mg (3000mg/m2) had no response. Patient was then received gemtuzumab ozagomycin 22mg (9mg/m2) on day 1 and 14. Bone marrow analysis 30 days after the treatment was consistent with remission. Interestingly patient developed little adverse effect from the initial induction chemotherapy. Hospital course was complicated with Clostridium difficile colitis and neutropenic fever which was treated with antibiotics and voricanazole. Voricanazole dosing was done according to the actual body weight (1000mg IV twice daily). The peak and trough levels were within normal range. Failed response to initial induction treatment could be due to refractory disease or inadequate dosing of chemotherapy in this patient. BSA has been used to calculate the dose in anticancer therapy since 1950s. Experimental studies have demonstrated BSA based dosing failed to standardize the variation in pharmacokinetics of cytotoxic drugs. In obese cancer patients, the pharmacokinetics of the drug demonstrated a prolonged elimination time for several agents. Risk of both under dosing and overdosing can have detrimental affect outcome in obese patients. Prospective studies of chemotherapy pharmacokinetics are needed to address the issue of optimal chemotherapy dosing in obese population.

Dilemmák egy új kezeléssel remisszióba hozott AML-beteg esete kapcsán: a kezelés intenciójának változása

2020 ◽  
Vol 53 (4) ◽  
pp. 196-200
Author(s):  
Ádám Kellner ◽  
Péter Rajnics ◽  
Balázs Kollár ◽  
Éva Karádi ◽  
Ibolya Ercsei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Wide Spectrum ◽  
Performance Status ◽  
Combined Treatment ◽  
Normal Karyotype ◽  
B Cell Lymphoma ◽  
Induction Treatment ◽  
High Dose ◽  
Anal Abscess

Összefoglaló. Az acut myeloid leukemia a csontvelői eredetű hemopoetikus őssejtek malignus klonális betegsége. A betegség lefolyása, különösen a nagy dózisú kemoterápiára és allogén csontvelő-transzplantációra alkalmatlan betegek számára, a legutóbbi időkig szinte kivétel nélkül fatális volt. Az idős és/vagy leromlott állapotú acut myeloid leukemiás betegek kezelésében óriási áttörést hozott a Bcl2- (B-cell lymphoma 2) inhibitor – venetoclax és a hypomethyláló azacitidin kombinációja. Ötvenéves nőbetegünkön a normál karyotípusú, nucleophosmin 1 mutációval járó acut myeloid leukemia diagnózisa előtt szeptikus állapotot okozó végbéltályog miatt tehermentesítő colostomaképzést végeztünk. A széles spektrumú kombinált antibiotikus kezelés mellett is súlyosan elesett, szeptikus állapotú betegen a nagy dózisú, kuratív indukciós kezelést nem tartottuk kivitelezhetőnek, ezért venetoclax–azacitidin kombinációt alkalmaztunk. A beteg az első ciklus alatt az antibiotikus, antimycoticus kezelés mellett masszív hemoszupportációra szorult. A második ciklus alatt lényeges szövődményt már nem észleltünk, a ciklus végén elvégzett csontvelővizsgálat pedig komplett hematológiai remissziót igazolt. A páciens önellátóvá vált, a végbéltályog jelentősen javult. Az új kezelési lehetőség mellett elért remisszió, a beteg javuló általános állapota korábban ismeretlen problémát vet fel. Egy 50 éves beteg jó prognózisú eltéréssel járó acut myeloid leukemiájának ellátása a nagy dózisú kemoterápiával elért első remisszióban nem igényel allogén csontvelő-transzplantációt. „Nem kuratív” kezeléssel elért remisszióban hogyan folytassuk a kezelést? Summary. Acute myeloid leukemia is a clonal malignancy of bone marrow haemopoietic stem cells. Until recently the outcome of the disease has been almost without exemption fatal, especially in cases ineligible for high dose induction chemotherapy and bone marrow transplantation. The Bcl-2 inhibitor venetoclax-azacitidine combination is a breakthrough therapy for the elderly and frail AML patient. Prior to the diagnosis of normal karyotype NPM 1 mutant AML of our 50-year-old female patient a colostomy had been performed due to anal abscess leading to sepsis. The septic patient being extremely frail in spite of wide spectrum antibiotic treatment was deemed ineligible for high dose curative induction treatment, hence venetoclax-azacitidine combined treatment was used. During cycle 1 the patient needed massive transfusion support beside concomitant antibiotic and antimycotic medication. On course of cycle 2 no major complications were detected, BM evaluation at the end of cycle confirmed complete haemotologic remission. The abscess significantly improved, the patient’s self-care capability was restored. The remission induced by this new option and the improvement of the performance status of the patient raised hitherto unasked questions. In case of a patient aged 50, a favourable prognosis AML in remission following high dose induction does not mandate HSCT as a next step. How shall we follow the course of treatment in remission elicited by a ‘non-curative’ option?

Hand-assisted laparoscopic nephrectomy in morbidly obese patients

2020 ◽  
Vol 99 (6) ◽  
pp. 271-276
Keyword(s):  
Body Weight ◽  
Surgical Technique ◽  
Blood Loss ◽  
Hospital Stay ◽  
Kidney Cancer ◽  
The Body ◽  
Laparoscopic Nephrectomy ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Morbid Obese

Introduction: Prevalence of obesity is 30 % in the Czech Republic and is expected to increase further in the future. This disease complicates surgical procedures but also the postoperative period. The aim of our paper is to present the surgical technique called hand-assisted laparoscopic nephrectomy (HALS), used in surgical management of kidney cancer in morbid obese patients with BMI >40 kg/m2. Methods: The basic cohort of seven patients with BMI >40 undergoing HALS nephrectomy was retrospectively evaluated. Demographic data were analyzed (age, gender, body weight, height, BMI and comorbidities). The perioperative course (surgery time, blood loss, ICU time, hospital stay and early complications), tumor characteristics (histology, TNM classification, tumor size, removed kidney size) and postoperative follow-up were evaluated. Results: The patient age was 38−67 years; the cohort included 2 females and 5 males, the body weight was 117−155 kg and the BMI was 40.3−501 kg/m2. Surgery time was 73−98 minutes, blood loss was 20−450 ml, and hospital stay was 5−7 days; incisional hernia occurred in one patient. Kidney cancer was confirmed in all cases, 48–110 mm in diameter, and the largest removed specimen size was 210×140×130 mm. One patient died just 9 months after the surgery because of metastatic disease; the tumor-free period in the other patients currently varies between 1 and 5 years. Conclusion: HALS nephrectomy seems to be a suitable and safe surgical technique in complicated patients like these morbid obese patients. HALS nephrectomy provides acceptable surgical and oncological results.

Assessing Safety and Efficacy of Lean Body Weight-Based intravenous Heparin Dosing in Obese and Morbidly Obese Patients

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 1010A ◽  
Author(s):  
Rachel Park ◽  
Scott Chelemer ◽  
Jason Varghese ◽  
Cheryl Leddy ◽  
Lewis Rose
Keyword(s):  
Body Weight ◽  
Lean Body Weight ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Safety And Efficacy ◽  
Intravenous Heparin

Ideal versus corrected body weight for dosage of sugammadex in morbidly obese patients

Anaesthesia ◽  
2011 ◽  
Vol 66 (8) ◽  
pp. 721-725 ◽  
Author(s):  
P. Van Lancker ◽  
B. Dillemans ◽  
T. Bogaert ◽  
J. P. Mulier ◽  
M. De Kock ◽  
...  
Keyword(s):  
Body Weight ◽  
Morbidly Obese ◽  
Obese Patients

scholarly journals High-Dose Chemotherapy with Bendamustin and Melphalan Improves the Rate of Complete Remission in Myeloma Patients in First Remission Compared to Standard Melphalan Alone

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Sarah Farag ◽  
Ulrike Bacher ◽  
Myriam Legros ◽  
Daniel Betticher ◽  
Jean-Marc Lüthi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Complete Remission ◽  
Median Time ◽  
Maintenance Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
First Line ◽  
Term Survival ◽  
Pulmonary Failure

Introduction: Consolidation of first-line induction treatment in myeloma (MM) patients (pts) with 200 mg/m2 melphalan chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) was established as standard of care three decades ago. However, definite cure in myeloma patients remains exceptional due to residual disease escaping intensive treatment, and almost all patients will ultimately relapse at earlier or later time points following ASCT. Thus, improving efficacy of HDCT in MM remains an unresolved issue. Methods: We performed a phase-II randomized trial comparing standard 200 mg/m2 Melphalan (Mel) HDCT to experimental HDCT treatment with 200 mg/m2 bendamustine, a bifunctional alkylating agent, given at days -4 and -3, combined with 200 mg/m2 melphalan split on days -2 and -1 at 100 mg/m2 (BenMel) before ASCT in MM pts. Patients had up to four cycles of first-line induction treatment with bortezomib, lenalidomide and dexamethasone. After ASCT, pts received lenalidomide maintenance treatment for two years. The primary endpoint was to show a 15% improvement of the rate of complete remission (sCR+CR) after HDCT with BenMel compared to Mel alone. MRD assessment from the bone marrow was performed by multiparameter flow cytometry after hematological engraftment following HDCT/ASCT. MRD negativity was defined as clonal plasma cells below 10(-5). Results: We randomized 120 myeloma pts (60 patients in each arm), with high-risk genetic abnormalities present in 21.3% of the patients. The median age was 63 years (range 35-74). The sCR/CR rate after ASCT before initiation of lenalidomide maintenance treatment was better in the BenMel arm compared to Mel alone (70.0% vs 51.7%; p=.039). The post-ASCT remission rates in detail were sCR 40.0% vs 31.7% (p=.341); CR 30.0% vs 20.0% (p=.205); VGPR 16.7% vs 33.3% (p=.035); and PR 13.3% vs 15.0% (p=.793). MRD negativity assessed in the bone marrow by flow cytometry was observed in 26 (45.6%) of the BenMel treated pts compared to 22 (37.9%) of the Mel pts. Median time until neutrophil engraftment was 11 days after BenMel vs 12 days after Mel (p=.096), and median time until platelet engraftment was 13 days in both arms (p=0.367); all pts had full engraftment of both cell lineages. Prolonged hospitalization duration was seen in BenMel pts (median 19 vs 18 days; p=.006) due to the longer BenMel treatment administration. Fully reversible acute renal insufficiency occurred in three (5%) BenMel pts compared to none of the Mel pts (p=.250). No treatment-related mortality was seen in both groups. ICU admissions were necessary in 3 pts (5%) in the BenMel group (ARDS, septic shock, pulmonary failure), and 2 Mel treated pts (3.3%; due to pulmonary failure and decompensated cardiomyopathy). The PFS rates at 12 months were 95% in BenMel pts and 91% in Mel treated pts (p=.551). OS at 12 months was 96% for both groups (p=.262), and median PFS and OS were not reached in both groups. Conclusions: Our data confirm that high-dose bendamustine combined with melphalan HDCT before ASCT in MM patients is safe and well tolerated. In particular, bendamustine-associated renal toxicity was manageable and reversible in all patients, and hematopoietic engraftment was comparable to standard melphalan HDCT. HDCT with BenMel improves the sCR/CR rate compared to standard melphalan alone. Thus, BenMel HDCT before ASCT warrants further investigation aiming to improve the long-term survival rates of MM patients, eventually combined with new maintenance strategies in the post-transplant period. Figure 1 Disclosures No relevant conflicts of interest to declare.

P0264ASSESSMENT OF GFR IN MORBIDLY OBESE PATIENTS USING DIFFERENT EQUATIONS: WHICH IS THE BEST?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alaa Sabry ◽  
Amir Basiony ◽  
Mohamed Kamal
Keyword(s):  
Body Weight ◽  
Creatinine Clearance ◽  
Glomerular Filtration ◽  
Total Body Weight ◽  
Lean Body Weight ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Morbidly Obese Patient ◽  
Gault Formula ◽  
Total Body

Abstract Background and Aims Obesity is a potent risk factor for the development of kidney disease. The prevalence of abdominal obesity in Egyptians based upon the European cut-off points was 30.2% for men and 70.9% for women. To detect the best formula for estimation of glomerular filtration rates in morbidly obese individuals. Method: In this prospective study 82 morbidly obese patients were included, Age: 15 to 65 years, Morbidly obese patient (BMI > 40 Kg/m2), Creatinine clearance calculated from a 24-h urine was done, Estimated glomerular filtration rate (eGFR): It was assessed to be correlated with creatinine clearance and detect the most suitable formula for morbidly obese patients. Cockcroft-Gault formula:  Cockcroft-Gault formula (for total body weight): ockcroft-Gault formula (for adjusted body weight): Cockcroft-Gault formula (for lean body weight), MDRD-eGFR (Modification of Diet in Renal Disease equation) (Shahbaz & Gupta, 2019), CKD-epidemiology (CKD-EPI): (Levey, et al, 2009) Results Demogrphic criteria of the studdied patients Conclusion: The equations that had the nearest values to creatinine clearance were CG-TBW-GFR and CGAjBW- GFR, both of them had a moderate reliability with more agreement for the CG-TBW-GFR equation . The CG-TBW-GFR formula was the most reliable one to measure GFR, followed by the CG-AjBW-GFR formula, while the CG-IBW, CG-LBW, MDRD-GFR and CKD-EPI-GFR formulae were not reliable at all .

scholarly journals Evidence for Complete Mutation Clearance in Normal Karyotype AML Patients with Very Long (> 5 years) Remissions after Chemotherapy Alone

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1503-1503
Author(s):  
Francesca Ferraro ◽  
Christopher A Miller ◽  
Nichole Helton ◽  
Robert S Fulton ◽  
Catrina Fronick ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Conflicts Of Interest ◽  
Normal Karyotype ◽  
Small Subset ◽  
High Dose ◽  
Primary Therapy ◽  
Intermediate Risk ◽  
Mutational Landscape ◽  
First Remission ◽  
The Mean

Abstract The fraction of patients with cytogenetically normal acute myeloid leukemia (AML) who have long (>5 years) first remissions after chemotherapy alone is estimated to be about 9.1% in young (<60 years) and 1.6% in older (>60 years) patients1; very few intermediate risk patients are therefore "cured" with chemotherapy alone. At this time, it is not yet clear whether these long remission patients are "living with disease", or whether all AML cells have been eliminated. Many people in complete morphologic remission have evidence for persistence of their ancestral and/or founding clones within the first 2-3 years after treatment, but genomic studies of very long first remissions have not yet been described. To determine whether patients with very long first remissions with chemotherapy alone clear their mutations, or are living with persistent disease, we performed an analysis of the mutational landscape and mutation persistence of 8 cases of normal karyotype AML with remissions of >5 years, and who received standard "7+3" induction and high dose cytarabine consolidation (3 to 4 cycles) as their primary therapy. All patients were diagnosed and treated at Washington University in Saint Louis; patient characteristics are summarized in Table 1. The mean age of patients at initial diagnosis was 43.5 years (range 19-63), and the mean time of follow up in first remission is currently 92 months (7.6 years) (range 62-146 months). To the best of our knowledge, none of the patients has relapsed to date. In every case, the day +14 bone marrow demonstrated ablation, and the day +28 bone marrow showed complete morphologic remission. For each case, we defined the mutational landscape at presentation with enhanced exome sequencing (235x coverage of the entire exome, and ~1008x coverage of recurrently mutated AML genes, as defined in the TCGA AML study). Each case had one or more recognized AML driver mutations, with a mean of 44 (range 31-64) somatic exome mutations (Table 1). The mutational spectrum at diagnosis was not statistically different from larger cohorts of intermediate risk AML patients with standard outcomes: 2 cases had mutations in DNMT3A, 6 had NPMc, 4 had NRAS, 3 had FLT3, 2 had WT1, 2 had STAG2, 2 had SLC43A3, and 2 had PTPN11 mutations. We were able to create probes for 225 mutations (mean of 28 per case, range 17-41) for analysis on the Haloplex platform; we used this platform to perform deep, error-corrected sequencing in one or more remission samples obtained from the bone marrow or peripheral blood of each patient after more than 1 year of remission. The mean depth of Haloplex coverage for all variants for all 8 samples was 1607x (range: 102-12,538x). Importantly, each sample had at least one AML-specific mutation assayed with a coverage depth greater than 3500x, yielding a sensitivity to detect 1 cell in 1,750 (0.06%). In the remission samples, 7/8 patients demonstrated complete clearance of all mutations in all samples tested, strongly suggesting that all AML cells had been eliminated by standard induction and consolidation therapies. In one case (868442), we detected a persistent ancestral clone in morphologic remission samples, harboring DNMT3AR882H (VAF 10.19% in long remission) and IRS2D106Y mutations (VAF 12.82% in long remission). These data suggest that a small subset of normal karyotype AML patients treated with chemotherapy alone may able to completely eradicate all AML cells. Although the mechanism is not yet clear (increased susceptibility to chemotherapy, immunologic surveillance of neoantigens, etc.), these data suggest that some patients in long remissions after chemotherapy do not have persistent subclinical disease, nor do they retain ancestral clones that could potentially contribute to relapse. In ongoing studies, our aim is to define biomarkers that can be used to prospectively identify this subset of patients, so that they can avoid the risk of allotransplantation in first remission. Reference:Vasu, Sumithira et al., Blood Advances 2.13 (2018): 1645-1650. Web. 31 July. 2018. Disclosures No relevant conflicts of interest to declare.

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