Perls Stain Grade in Bone Marrow Aspirate Correlates with Overall Survival in Low-Risk Myelodysplastic Patients

2020 ◽  
pp. 1-5
Author(s):  
Federica Pilo ◽  
Giovanni Caocci ◽  
Giannalisa Mele ◽  
Giorgio La Nasa
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Aspirate ◽  
Low Risk

scholarly journals Perl's Stain Grade in the Bone Marrow Aspirate Correlates with Overall Survival in Low Risk Myelodysplastic Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5517-5517
Author(s):  
Federica Pilo ◽  
Giovanni Caocci ◽  
Anna Angela DiTucci ◽  
Valentina Serreli ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Bone Marrow Aspirate ◽  
Bone Marrow Aspiration ◽  
Advisory Board ◽  
Low Risk ◽  
Iron Storage ◽  
Bone Marrow Iron ◽  
Grade 3

Abstract Background Myelodysplastic syndromes (MDS) are heterogeneous group of acquired clonal hematopoietic stem cell disorders characterized by atypical stem cells maturation and genetic instability leading to an enhanced risk of progression to acute myeloid leukemia. Low risk MDS patients have a lower probability to evolve in leukemia but are commonly characterized by dyseritropoiesis. These patient are incline to long term accumulation of iron in the organs due mostly to red blood cell transfusion (RBC) but iron overload may also occur in MDS patients who do not receive RBC transfusions due to the ineffective erythropoiesis. It is well known the effect of oxidant-mediated tissue's injury through the formation of free toxic iron species in the liver and heart site, but recent knowledges assumes that this mechanism is effective also in the bone marrow nice, where oxidative stress seems to impaired the haematopoietic stem cells growth. At this moment microscopic examination of the stainable iron in the bone marrow is considered the gold standard for determining the iron stores. The effect of bone marrow's iron overload on overall survival in the low risk MDS has been a matter of unresolved debate. We aimed to investigate the predictive value of bone marrow iron accumulation as demonstrated by Perl's staining on outcome in such patients. Design We retrospectively analyzed all low risk,intermediate-I MDS patients who had diagnosed in our institution in the last 20 years (since 1998). Diagnosis of MDS was made according to WHO criteria. Patients were stratified based on International Prognostic Scoring System (IPSS). Patients had undergone bone marrow aspiration as part of the diagnostic work up for their MDS. Two different experienced hematologist analyzed all samples. Bone marrow aspiration slides with at least seven fragments were considered suitable. Perl's Prussian blue stain was used to stain bone marrow, assessed by modified Gale's grading (Tab. 1) and then correlated with outcome. Patients and methods Marrow staining of one hundred and fourteen consecutive MDS patients were revised and analyzed. Median age was 70 years (range 32-93). Eighty three patients were IPSS low- risk and 30 Intermediate I. All patients were evaluated for bone marrow iron stores with Perl's stain. Twenty-seven patients had grade 1 (+), 31 grade 2 (++) and 56 grade 3 (+++). Patients had never or minimally received RBC . None of these patient had received iron chelation before marrow examination. Probability of overall survival (OS) was estimated by the Kaplan-Meier method and the significance was assessed by the log-rank test. Results 20-year OS was significantly lower in patients with higher Perl's score (median = 80 ±7 months in grade 3; median = 70 ±17 months in grade 2; median = 144 ±18 months in grade 1 , P=0.011); Fig. 1 Conclusions We evaluated retrospectively the bone marrow aspirate from 114 consecutive new MDS low-risk, Intermediate-I IPSS patients with Perl's stain for iron detection. Although Perl's grading is a qualitative method, it is still the gold standard to detect iron storage in the bone marrow. Our results correlate Perl's stain at diagnosis with long term outcome in MDS patients. We show how higher grade of iron storage at diagnosis can impact on outcome in these patients. We conclude that Perl's stain, together with Ferritin and blood transfusional burden could be another marker at diagnosis of iron-related toxicity that predict overall survival. Disclosures Pilo: Novartis Italy: Honoraria. Angelucci:Jazz Pharmaceuticals Italy: Other: Local ( national) advisory board; Vertex Pharmaceuticals Incorporated (MA) and CRISPR CAS9 Therapeutics AG (CH): Other: Chair DMC; Roche Italy: Other: Local (national) advisory board; Novartis: Honoraria, Other: Chair Steering Comiittee TELESTO Protocol; Celgene: Honoraria, Other: Chair DMC.

Bone Marrow Aspirate Can Be Avoided in Low-Risk MGUS Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3997-3997
Author(s):  
Silvia Mangiacavalli ◽  
Federica Cocito ◽  
Lara Pochintesta ◽  
Cristiana Pascutto ◽  
Alessandra Pompa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Aspirate ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Low Risk ◽  
Invasive Procedures ◽  
Diagnostic Work ◽  
Work Up ◽  
Diagnostic Work Up ◽  
Monoclonal Component

Abstract Abstract 3997 Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasmacell dyscrasia with a high prevalence. Diagnostic criteria include: presence of serum monoclonal component (MC) <30 g/l, <10% clonal plasma cells in the bone marrow (BMPC) and absence of end-organ damage according to CRAB criteria. Define the minimal diagnostic work up of patients with small amount of MC (<1.5 g/dl) at low risk for progression to multiple myeloma (MM) according to Mayo clinic stratification is still a matter of debate. This study assess the risk of missing a MM diagnosis not performing invasive procedures (bone marrow aspirate or biopsy) in presence of small amount MC. After approval by our local ethical committee, we retrospectively reviewed medical records of 2304 patients addressed to our single Hematology department for definition MC of IgG or IgA isotype. Diagnostic work-up included: bone marrow aspirate, skeletal bone survey and laboratory tests (i.e. complete blood count, chemistry screening including calcium and creatinine, serum protein electrophoresis and immunofixation, 24-hour urine electrophoresis for quantification of urinary monoclonal component). Patients were defined as having low-risk MC entity according to IMWG criteria (i.e. <1.5 mg/dl). There were 940 out of 2304 patients (41%) presenting with low-risk MC, among them a not negligible percentage (10%, 93 pts) encountered the criteria for MM after completing the scheduled diagnostic work-up. In detail 36% of them were asymptomatic, the remaining 64% presented at least one of CRAB criteria for active disease (60% had lytic lesions at skeletal survey). When adopting lower cut-off value of MC the criteria for MM were encountered in smaller amount of pts. In detail: 6% (30 out of 499 pts) and 4% (8 out of 206 pts) respectively for cut-off value at 1 or 0.5 g/dl respectively. Univariate analysis found a significant correlation between MC amount and BMPC either in MGUS (p<0.001) and MM patients (p<0.001). The probability of missing a MM diagnosis due to a set of value below a specified cut-off was assessed by means of a ROC curve analysis. The probability of finding a clonal BMPC infiltration ≥10% was of 15.4% keeping the serum MC cut-off value at 1.5 g/dl. The risk of missed MM diagnosis was significantly lower choosing low MC cut-off, with 7.5% and 2.8% risk of missed diagnosis for MC cut-off value of 1 g/dl and 0.5 g/dl respectively. Similar specificity value were found either when selecting patients with none of the CRAB criteria for symptomatic disease or with a IgA isotype. In conclusion our study showed a strict correlation between the amount of serum MC and BMPC infiltration. Excluding cases presenting with any of CRAB symptoms, the risk of missed MM diagnosis is very low (7.5%) in patients with a MC <1 g/dl, confirming the chance to avoid invasive procedures during diagnostic work-up of opportunely selected patients. Disclosures: No relevant conflicts of interest to declare.

Validation of the Low Risk Prognostic Scoring System (LR-PSS) in Patients with VERY Low, Low and Intermediate Risk IPSS-R Myelodysplastic Syndrome. Results from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2902-2902 ◽  
Author(s):  
Helena Pomares ◽  
Isabel Sánchez-Ortega ◽  
Esther Alonso ◽  
Javier Grau ◽  
Rafael F. Duarte ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myeloid Leukemia ◽  
Low Risk ◽  
Prognostic Impact ◽  
Score System ◽  
Free Survival ◽  
Kaplan Meier ◽  
Acute Myeloid

Abstract Background: Myelodysplastic syndrome (MDS) therapeutic decisions have been traditionally based on the IPSS; however, this score system does not allow the identification of patients with low risk disease (low or intermediate-1 IPSS) but a poor prognosis, who could benefit from an early intervention. Garcia-Manero et al (Leukemia 2008) described a specific prognostic scoring system for this subgroup of patients (LR-PSS) based on age ≥60 years, hemoglobin <10g/dl, platelet count <50k/uL or 50-200k/uL, bone marrow blasts ≥4% and unfavorable cytogenetics (non-del(5q), non-diploid). This LR-PSS score system enables the stratification of low risk MDS patients into 3 different risk categories; interestingly, the third category identifies a subgroup of patients with a median overall survival (OS) similar to that of patients classified as intermediate-2 and high risk IPSS. Besides, the IPSS-R described by Greenberg et al (Blood 2012) has demonstrated a strong prognostic value for OS and LFS as compared to the IPSS when applied to different independent series of MDS patients. The prognostic impact of the LR-PSS has not been analyzed in MDS patients with very low-, low- and intermediate IPSS-R scores. Aim: To analyze the prognostic impact according to OS and leukemia free survival of the LR-PSS when applied to a population MDS patients with very low, low and intermediate IPSS-R. Methods: A total of 789 consecutive patients diagnosed with MDS (01/1992-12/2014) at the Catalan Institute of Oncology of Barcelona were included in the study. 413 (52%) had available cytogenetics and therefore, IPSS-R was calculated. Overall, 371 (89%) patients were classified as very low, low and intermediate IPSS-R and included in the study. Results: 123 (30%) patients were classified as very low, 182 (44%) low and 66 (16%) intermediated IPSS-R risk MDS; median age 72 years (range 32-101) and 258 (69%) male. 1.4 % CRDU, 7.6 % RA, 41.6 % RCMD, 16.2 % RAEB‐1, 4.1 % RAEB‐2, 25.9 % CMML and 3.2 % MDS‐U with isolated 5q deletion according to the 2008 WHO classification. At diagnosis, median hemoglobin, platelet and bone marrow blast were 11.8 g/dL (5.5-17.1), 152 x109/L (1-1492) and 3 % (0-17), respectively and fifty-three (14.3 %) patients had unfavorable LR-PSS cytogenetics. For the whole population, median follow up was 6.6 years (range 6-7.7). At the time of last follow up, 48.2 % (179) had died and only 49 (13%) had progressed to acute myeloid leukemia. When the LR-PSS was applied to the very low, low and intermediate IPSS-R subgroups three well-differentiated prognostic categories could be identified: 58 patients (15.6%) category 1, scores 0-2; 277 (74.6%) patients category 2, scores 3-4 and 36 (9.8%) patients category 3, scores 5-7 with significantly different overall survival and leukemia free survival. Median OS for categories 1 (9.4 years; 95% CI 6.7-12), 2 (6 years; 95% CI 5-7.1) and 3 (2.6 years; 95% CI 2.1-3) were significantly different (p<0.001; Figure 1). Moreover, the rate of progression to acute myeloid leukemia was 5% (3/58), 13% (37/277) and 25% (9/36) for categories 1, 2 and 3, respectively. Summary/Conclusion: When applied to a low risk (very low, low and intermediate) IPSS-R cohort of MDS population, the LR-PSS identifies a subgroup of patients with a significantly worse prognosis who could benefit from an early intervention. Further studies are warranted. Fig 1. Kaplan-Meier survival for patients with very low-, low- and intermediate IPSS-R risk assigned to categories 1 to 3 by LR-PSS. Fig 1. Kaplan-Meier survival for patients with very low-, low- and intermediate IPSS-R risk assigned to categories 1 to 3 by LR-PSS. Disclosures Sureda: Takeda: Consultancy, Speakers Bureau.

scholarly journals Validation of Low Risk Prognostic Scoring System (LR-PSS) in Patients with Lower Risk IPSS-R Myelodysplastic Syndrome. Results from a Single Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4270-4270
Author(s):  
Montserrat Arnan Sangerman ◽  
Helena Pomares ◽  
Esther Alonso ◽  
Mercedes Galiano ◽  
Maite Encuentra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Scoring System ◽  
Lower Risk ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Low Risk ◽  
Acute Myeloid

Background: Myelodysplastic syndrome (MDS) therapeutic decisions have been traditionally based on the International Prognostic Scoring System (IPSS) (Greenberg et al, Blood 1997) and IPSS-R (Greenberg et al, Blood 2012). Recently, next-generation sequencing genetics has been incorporated into management of MDS, however its use is limited in routine clinical practice. Current prognostic models do not allow the identification of patients with low risk disease (low or intermediate-1 IPSS) and poor prognosis, who could benefit from an early intervention. Garcia-Manero et al (Leukemia 2008) described a specific prognostic scoring system for this subgroup of patients (LR-PSS) based on age ≥60 years, hemoglobin <10g/dl, platelet count <50k/uL or 50-200k/uL, bone marrow blasts ≥4% and unfavorable cytogenetics (non-del(5q), non-diploid). This LR-PSS score system enables the stratification of low risk MDS patients into 3 different risk categories; interestingly, the third category identifies a subgroup of patients with a median overall survival (OS) similar to that of patients classified as intermediate-2 and high risk IPSS. Besides, the IPSS-R described by Greenberg et al (Blood 2012) has demonstrated a strong prognostic value for OS and LFS as compared to the IPSS when applied to different independent series of MDS patients. The prognostic impact of the LR-PSS has not been analyzed in MDS patients with very low-, low- and intermediate IPSS-R scores. Aim: To analyze the prognostic value of Low Risk Prognostic Scoring System(LR-PSS) in a population of lower risk MDS patients (very low, low and intermediate IPSS-R) analyzing as endpoints overall survival (OS) and leukemia free survival (LFS). Methods: A total of 890 consecutive patients with MDS (01/1992-7/2018) diagnosed at the Catalan Institute of Oncology in Barcelona were included in the study. 539 (60%) had available cytogenetics and therefore, IPSS-R could be assessed. 474 (88%) patients were classified as very low, low and intermediate IPSS-R and were included in the study. Results: 178 (37.6%) patients were classified as very low, 219 (46.2%) low and 77 (16.2%) intermediated IPSS-R risk MDS. Median age at diagnosis was 73 years (range 32-101). 332 (70%) were male. According to the 2008 WHO classification, 2.5% CRDU, 7.4% RA, 42.2% RCMD, 13.7% RAEB‐1, 3.6% RAEB‐2, 26.4% CMML and 4.2% MDS‐U with isolated 5q deletion. At diagnosis, median hemoglobin, platelet and bone marrow blast were 11.6 g/dL (5.5-17.1), 157 x109/L (1-1492) and 2 % (0-17), respectively. 84 (17.7%) patients had unfavorable LR-PSS cytogenetics at diagnosis. Median follow up time for survivors was 5.4 years (range 0.25-23.8). At the time of last follow up, 58.4 % (277) had died and 71 (15%) had progressed to acute myeloid leukemia. When the LR-PSS was applied to the very low, low and intermediate IPSS-R subgroups, three well-differentiated prognostic categories could be identified: 103 patients (21.7%) category 1 (scores 0-2); 330 (69.6%) patients category 2 (scores 3-4) and 41 (8.7%) patients category 3 (scores 5-7) with significant different OS and LFS. Median OS for categories 1, 2 and were 7.1 years (95% CI 4.9-9.2), 5.7 years (95% CI 4.7-6.7) and 2.8 years (95% CI 2.1-3.6), p<0.001 (Figure 1), respectively. Rate of progression to acute myeloid leukemia was 10% (10/99), 15% (48/323) and 27% (11/411) for categories 1, 2 and 3, respectively. Summary/Conclusion: When applied to a low risk (very low, low and intermediate) IPSS-R cohort of MDS population, LR-PSS identifies a subgroup of patients with a significantly worse prognosis who could benefit from an early treatment intervention. Disclosures Sureda: Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead: Consultancy; Roche: Honoraria; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

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