The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

Abstract Abstract 4476 Hematopoietic Stem Cell Transplantation (HSCT) from partially HLA-matched (haploidentical) family donors represents a promising therapy for high-risk acute myeloid leukemia (AML). However, for patients with AML relapsed after HSCT from an HLA-mismatched familial donor, there is no standard therapy. They may receive conventional chemotherapy, cyclosporine withdrawal, second HSCT, and donor leukocyte infusion (DLI) with or without prior mobilization. Recently, combination chemotherapy and DLI showed achieving hematologic remission. We report a case of successful combination chemotherapy and donor leukocyte infusions from original donor in a patient with AML relapsing 6 years after HSCT from an HLA-Mismatched Familial Donor. A 37-year-old male presented with fever in June 2003.Bone marrow aspirate confirmed the diagnosis of AML(M5 subtype according to FAB classification). The patient initially received intensive chemotherapy. However, the patient with AML that was refractory to conventional therapy. He received HSCT in first CR from his mother 1-loci HLA-mismatched (HLA-A) using BuCY- Conditioning regimen on June 11, 2004. He showed a medullary relapse 6 years after HSCT. His bone marrow blast counts exceeded 80% with 8.25% of donor karyotypes (46 XX FISH). We decided to try to use his mother as the donor for DLI. Cytoreductive chemotherapy was commenced prior to DLI. He was treated twice with DLI on August 02, 2010 and September 23, 2011. He was treated chemotherapy before in first DLI, chemotherapy regimens; FLAG-ida [fludarabine 30 mg/m2/d from day-6 to-2 of cell infusion, cytosine arabinoside 2 g/m2/d from day-6 to-2 of cell infusion, idarubicine 20 mg/d day-1 and G-CSF 300μ g/day from day-7 to +30]. The donors received G-CSF 10μ g/kg subcutaneously daily starting day-3 of cell infusion for 5 days. Donor peripheral blood mononuclear cells were collected by CS-3000 Plus cell separator (Baxter Corp.) on the fifth days of G-CSF administration and infused through a central venous catheter into the patients on the same day. 8.33×107/kg mononuclear cells, 6×107/kg CD3+ cells were reinfused without manipulation. Cyclosporine at the dose of 3 mg/kg were administered for the prevention of GVHD. On days 36 Bone marrow blast counts exceeded 45% with 44% of donor karyotypes (46 XX FISH) after first Chemo-DLI. He received cyclosporine withdrawal. He was treated chemotherapy by low-dose Ara-C and aclarubicin with concomitant use of G-CSF before in second DLI.,chemotherapy regimens;CAG[ Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days-14 to-1. Aclarubicin was administered intravenously at a dosage of 7 mg/m2 on days-14 to-7. Recombinant G-CSF was given subcutaneously at a dosage of 200μ g/m2 per day on days-14 to-1]. On day 0,1.4×108/kg mononuclear cells,1×108/kg CD3+ cells were reinfused. On days 25 bone marrow examination showed CR with 89% of donor karyotypes (46 XX FISH). He was treated consolidation chemotherapy by regimens; CAG.On days 62 bone marrow examination showed CR with 100% of donor karyotypes (46 XX FISH). He developed chronic GVHD with limited disease at day 123 of DLI. In the patient whose cGVHD resolved with the use of steroid, cyclosporine plus methotrexate. The patient died from pneumonia without evidence of recurrent leukemia on day +230. From the cases reported, combination chemotherapy and subsequent mobilized DLI produced a CR with AML in relapse six years after HLA-Mismatched transplantation. We demonstrate that of the patient who relapsed after 6 years, treatment with chemotherapy followed by intensive chemotherapy followed by DLI, can effectively salvage a patient with attainment of durable remissions. Although limited by the small number of one patient, AML in relapse six years after HLA-Mismatched transplantation requires particular attention in future studies, as well as in designing future treatment programs. Clearly a large number of patients is required to confirm the real efficacy of this treatment. Disclosures: No relevant conflicts of interest to declare.

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Effect of Complete Remission Achievement on Survival In Acute Myeloid Leukemia of the Elderly.

Blood ◽

10.1182/blood.v116.21.1048.1048 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1048-1048

Author(s):

Felicetto Ferrara ◽

Cira Riccardi ◽

Salvatore Palmieri ◽

Tiziana Izzo ◽

Antonella Carbone

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Complete Remission ◽

Myeloid Leukemia ◽

Normal Karyotype ◽

Loading Dose ◽

Refractory Disease ◽

Bone Marrow Blast ◽

Blast Count ◽

Acute Myeloid

Abstract Abstract 1048 The achievement of complete remission (CR) is considered an essential prerequisite for cure in acute myeloid leukemia (AML). Notwithstanding, in older AML patients recent data suggest that, at least for patients receiving new compounds such as hypomethilating agents Azacytidine and Decitabine, the benefit on survival can be independent from CR achievement, namely in patients with low bone marrow blast count (< 30%) at diagnosis. In this study we evaluated the impact of CR achievement on overall survival from a series of 140 patients aged over 60 years; all patients received a therapeutic program including continuous infusion of fludarabine (F) and cytarabine (ARA-C) as induction and consolidation, followed whenever possible by autologous stem cell transplantation (Ferrara et al, Haematologica, 2005). Briefly, F was administered at a loading dose of 10 mg/m2 over 15 min at day 0 followed 6 hours and half later by continuous infusion (c.i.) of 20 mg/m2/24 hours for 72 hours (days 0–2); ARA-C was given at a loading dose of 390 mg/m2 three hours and half after F and then as c.i. over 96 hours at 1440 mg/m2/24 hours (days 0–3). G-CSF was added at day +15 at a dose of 5 μg/kg. A second identical course was planned for patients obtaining partial response, defined as less than 5% blasts in peripheral blood and less than 30% of blasts in the bone marrow. Patients achieving CR, established as less than 5% blasts in the bone marrow, normal blood count and differential and absence of extramedullary leukemia, were programmed to receive an additional identical course as consolidation, reduced of one day (i.e. two days c.i. of F and three days c.i, of ARA-C). The effect of CR was separately analyzed according to karyotype, bone marrow blast count and, in patients with normal karyotype, NPM1 and FLT3 positivity. Of note, patients dead in induction were excluded from survival benefit evaluation. The median age was 69 years (range 61–82). Cytogenetic analysis was successfully in 134/140 patients (96%). Among these 89 (66%) were found as having normal karyotype (NK) and 45 (34%) with different chromosomal abnormalities, mostly complex or involving chromosomes 5 and/or 7, classified as unfavorable (UK). Overall 94 patients (67%) achieved CR; the CR rate was 77 % in NK and 47% in unfavorable karyotype (p:<0.001). Of note, rates of either death in induction (22% vs 14%) or primary refractory disease (33 % vs 8%) were significantly higher in patients with adverse cytogenetics. The median survival for the whole patient population was 10 months; survival was significantly influenced by cytogenetics at diagnosis (12 months for NK vs 7 months for UK), p:<0.001). The median duration of CR was 11 months (16 months for patients with NK as opposed to 7 months for those with UK). The overall impact of CR achievement on survival was remarkable and remained statistically significant after exclusion of patients dead in induction (18 months vs. 6 months, p:< 0.001). The advantage of achieving CR was found in patients with NK, independently from molecular assessment at diagnosis, i.e. NPM1+/FLT3-, NPM1-FLT3-, NPM-FLT3+, NPM+/FLT3+). Of interest, no difference was found as bone marrow blast count at diagnosis, i.e. more or less than 30 %, was concerned in the rate of CR achievement, CR duration and impact of CR on survival either in univariate or multivariate analysis. By separately analyzing patients with UK, the advantage of CR achievement was found only when patients dead in induction were excluded and was limited to 4 months (11 months for remitters vs. 7 months for refractory patients, p:0.04). We conclude that older AML patients with unfavorable karyotype have lower CR rates following conventional chemotherapy, because of higher mortality in induction and more frequent refractory disease; in addition, CR is shorter when compared to patients with normal karyotype and has limited impact on survival. Accordingly, even when clinically eligible for aggressive chemotherapy, such patients should be included into therapeutic programs based on experimental programs including agents with alternative mechanisms of action. Disclosures: No relevant conflicts of interest to declare.

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Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia

Blood ◽

10.1182/blood.v83.6.1603.bloodjournal8361603 ◽

1994 ◽

Vol 83 (6) ◽

pp. 1603-1611 ◽

Cited By ~ 127

Author(s):

A Neubauer ◽

RK Dodge ◽

SL George ◽

FR Davey ◽

RT Silver ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Univariate Analysis ◽

Bone Marrow Blast ◽

Ras Mutations ◽

Ras Genes ◽

Oligonucleotide Hybridization ◽

Acute Myeloid

Mutations of the N- and K-ras genes are the most frequent genetic aberrations in acute myeloid leukemia (AML) and their detection in preleukemic conditions such as the myelodysplastic syndrome (MDS) suggests a role in the earliest phases of leukemogenesis. Despite these observations, little is known about the clinical importance of ras mutations in AML. We studied the clinical impact of ras mutations in 99 patients with de novo AML. All patients were treated in two prospective multicenter trials. The polymerase chain reaction was used to amplify areas surrounding the codons 12, 13, and 61 of the three ras genes N-, K-, and H-ras from DNA from bone marrow cells, ras mutations were detected by an algorithm based on allele-specific oligonucleotide hybridization. Eighteen of 99 (18%) patients harbored mutations in either N- or K-ras. All of the observed mutations occurred in N-ras (N = 10) and K-ras (N = 5) or concurrently in both N- and K-ras (N = 3). There were no significant differences between ras-negative and ras- positive patients according to age, sex, blood counts, cytogenetic abnormalities, or French-American-British classification. However, univariate analysis suggested a longer survival in ras-positive patients (P = .11). When adjusted for age, which was the most important factor affecting outcome, the presence of a ras mutation emerged as a significant predictor for improved survival (P = .03) and along with lower bone marrow blast counts (P = .02) and better cytogenetic category (P = .01). However, the presence of an aberrant ras allele was strongly correlated with lower bone marrow blast counts (P = .007). Thus, whether a mutation in the N-ras or K-ras proto-oncogenes directly affects treatment outcome or indirectly through an association with lower leukemic burden remains to be determined. Nevertheless, these findings counter the prevailing bias that oncogene mutations lead to more aggressive behavior in human malignancies.

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Predictors of Outcome In Adult Patients with Acute Myeloid Leukemia In First Relapse,

Blood ◽

10.1182/blood.v118.21.3569.3569 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3569-3569

Author(s):

Farhad Ravandi ◽

Stefan Faderl ◽

Sherry Pierce ◽

Guillermo Garcia-Manero ◽

Mark Brandt ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

Predictors Of Outcome ◽

Bone Marrow Blast ◽

First Relapse ◽

Acute Myeloid

Abstract Abstract 3569 Treatment of patients with acute myeloid leukemia (AML) in first relapse has remained challenging and although relatively high response rates have been reported using selected combination chemotherapy regimens, long term leukemia-free survival has been less than 20% in most studies. A number of predictors of outcome have been reported of which the most significant are duration of first CR (CR1), cytogenetics at diagnosis, age at relapse, and whether allogeneic stem cell transplant (SCT) was performed in CR1 (Breems, DA, JCO, 2005). We sought to examine predictors of outcome after first relapse of AML incorporating some of the more recent relevant covariates such as molecular data, when available. From January 2000 to March 2010, 447 patients with AML (excluding acute promyelocytic leukemia) in first relapse were seen at the University of Texas – MD Anderson Cancer Center (MDACC) and have available survival data; 275 received therapy at MDACC and 66 (24%) achieved a second CR (CR2), with 14 (5%) patients achieving CR without platelet recovery (CRp2). For the overall population, the median survival from relapse is 5 months (range, 1 to 103+) and the median follow-up in surviving patients is 34.3 months (range, 5 to 103+). On univariate analysis, the following factors predicted survival in first relapse: the duration of CR1 (p<0.001), unfavorable cytogenetics at diagnosis (p<0.001) and having NPM1+/FLT3- status at diagnosis (p=0.001), as well as the following variables at relapse: age (p< 0.001), WBC (p<0.001), platelets (p=0.005), peripheral blood blast % (p<0.001), bone marrow blast % (p<0.001), performance status (p<0.001), creatinine (p<0.001), LDH (p<0.001) and albumin (p<0.001). Having FLT3-ITD at diagnosis and undergoing allogeneic stem cell transplant in CR1 were of borderline significance (p value for both =0.08). On multivariate analysis, taking into account only variables with a p<0.1, duration of CR1, age at relapse, unfavorable cytogenetics at diagnosis, and LDH as well as bone marrow blast % at relapse were significant (p<0.001). Positive FLT3-ITD at diagnosis was also significant (p=0.04). When multivariate analysis was conducted in the subset of 121 patients with complete FLT3 and NPM1 mutational status at diagnosis, neither the NPM1+/FLT3- status, nor having FLT3-ITD at diagnosis remained significant. In conclusion, we confirm that the most important predictors for survival in first relapse are duration of CR1, age at relapse, unfavorable cytogenetics, and possibly FLT3-ITD at diagnosis, as well as percentage of bone marrow blasts and LDH at relapse. Disclosures: No relevant conflicts of interest to declare.

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Azacitidine Alone Or The Combination With Valproic Acid As a Bridge Therapy For Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes Before Transplantation

Blood ◽

10.1182/blood.v122.21.2812.2812 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2812-2812

Author(s):

Cristina Calderón Cabrera ◽

Jose F Falantes ◽

Marina Gómez ◽

Rocío Parody ◽

Francisco J Márquez Malaver ◽

...

Keyword(s):

Bone Marrow ◽

Valproic Acid ◽

Acute Myeloid Leukemia ◽

High Risk ◽

Myeloid Leukemia ◽

Refractory Anemia ◽

Intensive Chemotherapy ◽

Bone Marrow Blast ◽

Acute Myeloid

Abstract Introduction Intensive chemotherapy (IC) followed by allogeneic stem cell transplantation (AlloSCT) is standard of care for intermediate and high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS). However, morbidity and lack of response are common with IC. Retrospective data have shown similar outcomes with azacitidine (AZA) when compared to IC. Moreover, the combination of AZA with other epigenetic modifiers such as HDAC inhibitors seems to improve quality of responses. Aim Evaluate response, toxicity and feasibility of AlloSCT after AZA alone or the combination with valproic acid (VPA) as a bridge strategy in MDS and AML. Patients Nineteen consecutive patients (pts) receiving azacitidine alone (n=11) or in combination with valproic acid (VPA) (n=8) were analyzed. Median age of the cohort was 57 years (18-67). Diagnosis by WHO classification included: RAEB-2 (n=10/19; 52.6%), RAEB-1 (n=2; 10.5%), RCMD (n=2; 10.5%) and AML (n=5; 26.3%). Four out of 5 AML pts had bone marrow blast count >30% at diagnosis. In MDS patients, according to International Prognostic Scoring System (IPSS): 1 intermediate-1 (7%), 3 intermediate-2 (21.5%) and 10 high-risk (71.5%) and by IPSS-revised (IPSS-R): 1 intermediate (7%), 4 high (29%) and 9 very high (64%). Regarding karyotype, in MDS: 5 good (35.7%), 2 intermediate (14.3%), 6 poor (43%) and 1 insufficient metaphases (7%) whereas in AML Patients 1 intermediate (20%) and 4 adverse (80%). Eleven out of 19 pts (58%) received AZA as frontline therapy. The remaining 8 pts experienced disease relapse after intensive chemotherapy (IC) or had primary refractory AML, and subsequently received AZA plus VPA as salvage therapy. Median courses of previous IC were 2 (1-4). For pts receiving AZA/VPA, median bone marrow blast % and leukocyte were 31% (2-60) and 1.9x10e9/L (0.3-4.2) when therapy started. Most of these pts had refractory or relapsed disease (n=6/8; 75%) with 4 pts displaying poor karyotype. Treatment schema was AZA (75 mg/m2, 7d/4w) and VPA (20-25 mg/kg/d, 10 days). Results At analysis, 17/19 pts are evaluable for response. Median courses of AZA: 5 (2-53). Overall response (ORR) at 4 courses: 59% (CR=4/17; 23.5%, CRm=5/17; 29.5% and PR=1/17; 6%). For pts receiving AZA/VPA (Table 1, n=8), ORR: 83% (CR=1/6; 17% and CRm=4/6, 66%) in 6 evaluable pts. Median courses to response were 2. Among pts achieving CR/CRm/PR/SD at 4 courses (n=12), 2 pts lost response prior to AlloSCT. Most frequent toxicity was hematological (58% grade 3-4) with no treatment related mortality attributable to AZA/VPA. Eleven out of 19 pts (58%) received AlloSCT (matched related=5, matched unrelated=5, haploidentical=1). Causes for not proceeding to AlloSCT: Disease progression (n=4; 50%), infection (n=1; 12.5%), pending evaluation after 2 courses (n=2; 25%) and 1 pt (12.5%) scheduled for matched unrelated AlloSCT. Conditioning regimen: Reduced intensity (9/11) and myeloablative (2/11). Tacrolimus/sirolimus (50%) and cyclosporine/MMF (40%) as GVHD prophylaxis. With a median follow-up of 4 months after AlloSCT (1-26), only 1 pt developed acute GVHD, 1 had early relapse postransplant and 9 patients continue in CR at last follow up. Conclusions AZA alone and particularly the combination AZA/VPA prior to AlloSCT is a well-tolerated and highly effective schema even in pts with poor prognostic features and refractory to prior IC. Adequate selection of pts (leukocyte <10x10e9/L) and larger prospective studies are needed to assess the role of this strategy. AML; Acute myeloid leukemia, RAEB-2; Refractory anemia with excess blasts type 2, RAEB-1; Refractory anemia with excess blasts type 1, IM; Insufficient metaphases, IC; Intensive chemotherapy, CR; Complete response, CRm; marrow CR, NA; Not assessable (pending bone marrow evaluation). 1Refractory to IC. 2Relapsed after IC. aBone marrow evaluation after 2 and 4 courses of therapy Disclosures: No relevant conflicts of interest to declare.

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PB1738 NUCLEOPHOSMIN-1 GENE MUTATION DETECTION: COMPARATIVE IMMUNO-STAINING STUDY FOR BONE MARROW (BM) BIOPSY VERSUS BM ASPIRATE & BM CLOT IN DE NOVO ADULT ACUTE MYELOID LEUKEMIA PATIENTS AMONG EGYPTIANS

HemaSphere ◽

10.1097/01.hs9.0000565460.27242.5c ◽

2019 ◽

Vol 3 (S1) ◽

pp. 799-780

Author(s):

B. Elgamal ◽

M. El Gammal ◽

R. Badawy ◽

E. Abdelghaffar ◽

E. Rasheed ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Gene Mutation ◽

Myeloid Leukemia ◽

Mutation Detection ◽

De Novo ◽

Acute Myeloid

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Donor T-Cell Chimerism Does Not Predict Relapse and Response to Donor Lymphocyte Infusion for a Patient of Secondary Acute Myeloid Leukemia after Reduced-Intensity Allogeneic Hematopoitic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v108.11.5338.5338 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5338-5338

Author(s):

Xiaowen Tang ◽

Qiurong Zhang ◽

De Pei Wu ◽

Yufeng Feng ◽

Aining Sun

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Stem Cell ◽

Myeloid Leukemia ◽

Donor Lymphocyte Infusion ◽

Blast Cell ◽

Donor Chimerism ◽

Secondary Acute Myeloid Leukemia ◽

Reduced Intensity ◽

Acute Myeloid

Abstract We analyzed donor chimerism(DC) in unfractionated(UF) and CD3+ cells from a secondary acute myeloid leukemia patient who relapsed after reduced-intensity allogeneic hematopoitic stem cell transplantation(RIST) and had undergone donor lymphocyte infusion(DLI). Sequential and quantitative chimerism was performed by multiplex PCR amplification of STR markers (STR-PCR). The peripheral blood(PB) every 3 days and bone marrow every week were collected for chimerism analysis. The patient presented hematological relapse 26 months after the first RIST. There were 31.5% blast cell in the bone marrow smear and presented additional abnormal chromosome [44,XY,-7,dic(16,17)]. While UF donor chimerism from PB and CD3+ fraction donor chimerism from PB and BM were always full donor chimerism (range, 96.4%~98.1%). However UF chimerism from BM was 64.9% at the same time point. Afterwards the patient received 4 times of dose-escalated donor lymphocytes infusion (DLI) with CD3+ cell from 1*107/kg to 1.0*108/kg. Unfortunately the patient hasn’t response to this therapy. The blast cell in BM smear augment from 31.5% to 51.5%. UF chimerism from BM ranged from 55.2 to 46.5%. But UF DC from PB and CD3+ fraction DC from PB and BM ranged from 95.5% to 98%. In conclusion, Our result suggest that in this AML patient the donor T-cell chimerism and unfractionated chimerism in PB can not predict relapse and response to donor lymphocyte infusion. and the reason is not clear.

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A Unified Prognostic Model for Myelodysplastic Syndrome and Acute Myeloid Leukaemia Based on Flow Cytometric Blast Count

Blood ◽

10.1182/blood.v118.21.1736.1736 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1736-1736

Author(s):

Alexandra Smith ◽

Simon Crouch ◽

Dan Painter ◽

Eve Roman ◽

Matt Cullen ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndrome ◽

Cell Count ◽

Prognostic Model ◽

Blast Cell ◽

Bone Marrow Blast ◽

Flow Cytometric ◽

Blast Cells ◽

Blast Count ◽

Acute Myeloid

Abstract Abstract 1736 The distinction between Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndrome (MDS), together with its prognostic assessment, depends on the proportion of bone marrow blast cells. The International Prognostic Scoring System (IPSS) uses this value to predict survival in conjunction with cytogenetic and blood count parameters. Current practice in most centres is to count blast cells manually on stained smears and to assign patients to one of 4 bands (<5%, 6–10%,11-19% and >20%). This approach has two major disadvantages. Firstly, the evaluation of cellular morphology is subjective and the standard error of a manual count is sufficiently large that many patients cannot be assigned with reasonable accuracy to a category - which can critically impact on their care. Secondly, assigning patients into broad groups, instead of retaining blast cell count as a continuous variable, may be degrading important prognostic information. Modern flow cytometric techniques allow blast cells to be counted with high levels of accuracy. In this study we used a standard five colour assay including CD34, CD117, CD15, CD3, CD19 and physical characteristics to count bone marrow blast cells. Bone marrows from 271 patients with AML/MDS treated with curative intent (median age, 59 yrs; M: F,1.22) and 684 patients treated with supportive therapy (median age, 77 yrs; M: F,1: 1.8) were evaluated. Patients with acute promyelocytic leukaemia (APML), AML with t(8;21) or inv 16 were excluded. All patients were from a population-based cohort (www.hmrn.org), and all diagnostic studies were performed using standard protocols in a single laboratory. A prognostic model was constructed using age, flow cytometric blast cell count and gender. In non-intensively treated patients survival declined rapidly with blast counts up to 10% and then decreases much more slowly. Age had a minimal effect on survival under the age of 70, but prognosis declined rapidly in older patients. Male gender was a significant adverse risk factor (hazard ratio = 1.47). In contrast, patients who were treated intensively showed only a modest relationship between blast count and prognosis but a much more marked effect of age. Survival declined progressively from 20 years with the trend accelerating in those over 60 years. There was also a smaller effect of gender in those receiving intensive treatment (hazard ratio = 1.09). In MDS patients, a complex relationship between blast cell count, standard cytogenetic risk factors and the degree of cytopenia was observed. Using age and flow cytometric blast count as continuous variables, modelled using restricted cubic splines, together with gender enabled more accurate outcome prediction in patients with AML and MDS across the full range of blast counts. This is possible because of the much higher levels of accuracy of flow cytometry compared to manual counting methods. The main practical advantage of a unified prognostic model is that it allows the relative benefits of intensive and non-intensive treatment to be readily compared for an individual patient. The predictive power of this core model can be improved further by the inclusion of additional clinical and molecular data. MDS and most forms of AML are part of a continuous spectrum of disease. A more unified approach to classification avoiding arbitrary subdivision may improve clinical decision making in this complex group of patients. Figure: The interrelationship between survival, age and blast cell count in patients with myelodysplastic syndrome. Figure:. The interrelationship between survival, age and blast cell count in patients with myelodysplastic syndrome. Disclosures: No relevant conflicts of interest to declare.

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