bluuebunny/crossref_metadata_2025 huggingface dataset:
PB1665 TREATMENT OF FAVORABLE RISK YOUNG PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) USING A LOW‐DENSE/ LOW‐INTENSE CHEMOTHERAPY PROTOCOL
Authors: Salamoon M. , balti M. , ghanem K. , kenj M.
Published: June 2019

Background:

ALL is a disease affecting the lifespan from neonates to elderly, however, overall survival reaches 90% using pediatric protocols. In older patients, survival is still very poor reaching only 45% which can be attributed to several reasons including heterogeneity of biology, physiologic status of patients as well as therapeutic approach. Another factor justifying the poor outcome is the low rate of enrollment in clinical trials of this population aged between 15‐39 years as defined by the National Cancer Institute (NCI).

Aims:

the study evaluates the response rate, progression free survival (PFS) and overall survival at % years (OS) as well as the safety profile.

Methods:

this is a multicenter study performed in part at Al Bairouni university cancer center, Al Mwasat charity and Ospedale Italiano in Damascus, Syria between 2008 and 2013 where we recruited 224 patients having a favorable risk ALL confirmed by Bone Marrow aspiration (morphologic study, Flocytometeric study and Karyotype) was performed in all patients. Induction with (Dxorubicin 45 mg/m2+ Cyclophosphamide 75 mg/m2+ Vincristin 1.4 mg/m2) every weeks X 4 weeks and prednisolone 1 mg/kg for 4 weeks. Complete responders consolidated with 1st block: Cyclophosphamide 75 mg/m2+ Cytarabine 30 mg/m2 BID/SC for 5 days+ 6‐Mercaptopurine 75 mg/m2 every day repeated every 14 days 4 times followed by a 2nd block: Methotrexate 3 gram/m2+ Kidrolase 10000IU repeated every 14 days for 4 times. Maintenance with cyclophosphamide 750 mg/m2+ Vincristin 1.4 mg/m2+ oral Methotrexate 15 mg + 6‐Mercaptopurine daily, repeated every month for 24 times. Intralthecal prophylaxis with Methotrexate as performed 2 times in the induction, with every consoloidation and every 3 month during maintenance.

Results:

complete remission in the first induction was seen in 185 patients (82.5%) with other 32 joined them after an extra induction round (96.8%). Only 8 patients progressed in the consolidation period versus 10 in the maintenance with a PFS of 88.9% at 5 years and 202 patients still surviving after 5 years with an overall survival rate of (90.17%). We have lost 4 patients in the induction and 2 in the consolidation due to unusual toxicity profile of Methotrexate, however, other toxicities were manageable. Response was more prominent in younger population (those younger than 22) (p value 0.003) and late in those with Philadelphia positive disease (p value 0.02).

Summary/Conclusion:

ALL is still a lethal disease especially in those who do not respond well to induction protocols. Progress was made during the last decade in both understanding the biology and employment of new treatment approach especially in pediatric population, however, results are still poor in elderly patients. Our study shows good results compared with published data which could be adopted in the light of other trials conducted to test our results.
PB1675 ASSESSMENT OF SERUM IL‐15 IN ADULT ACUTE LEUKEMIA PATIENTS (EGYPTIAN SAMPLE)
Authors: Moussa M.M. , Sheeba M. , Elmohsen E. Abd , Elshazly M. , Hussein N.E.
Published: June 2019

Background:

Interleukin 15 (IL‐15), a proinflammatory cytokine, regulates the functions of the immune system and controls the differentiation of hematopoietic cells. However, it may also promote the development of leukemia through its role in enhancing the survival, proliferation and differentiation of leukemic precursors.

Aims:

To assess expression of IL‐15 level in adult Egyptian acute leukemia patients, its correlation with disease free survival, overall survival and relapse rate, as well as its possible correlation with other prognostic parameters.

Methods:

Serum IL‐15 level was measured using enzyme‐linked immunosorbent assay in 30 newly diagnosed acute lymphoblastic leukemia (ALL) patients, 30 newly diagnosed acute myeloid leukemia (AML) patients and 30 age and sex‐matched healthy control subjects. The patients were recruited from clinical hematology department at Ain shams university hospital over the period from April 2017 to October 2018.

Results:

In ALL patients: The serum IL‐15 level was higher in ALL patients compared to control subjects (P = 0.015). The serum IL‐15 level was higher in ALL patients with non high risk cytogenetics compared to those with high risk cytogenetics (P = 0.047). Patients with ALL with high serum IL 15 level achieved 1stcomplete response (CR) less than those with low or average serum IL 15 level (P = 0.038). Patients with ALL with high serum IL 15 level achieved minimal residual disease (MRD) negativity less than those with low or average serum IL 15 level (P = 0.006). Patients with ALL with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P = 0.005). The optimal cut‐off value for serum IL‐15 in predicting patient survival in patients with ALL was 200 ng/L.

In AML patients: The serum IL‐15 level was higher in AML patients compared to control subjects (P =  0.010). The serum IL‐15 level was higher in AML patients with high risk features compared to those with non high risk features (P = 0.048). Patients with AML with high serum IL 15 level achieved 1stcomplete response (CR) less than those with average serum IL 15 level (P = 0.015). Patients with AML with high serum IL 15 level achieved minimal residual disease (MRD) negativity less than those with average serum IL 15 level (P = 0.002). Patients with AML with high serum IL 15 level had shorter survival compared to those with low or average serum IL 15 level (P < 0.001). The optimal cut‐off value for serum IL‐15 in predicting patient survival in patients with AML was 190 ng/L. Serum IL15 level has negative correlation with the date of death in patients with AML (P =  0.001).

Summary/Conclusion:

Interleukin 15 (IL‐15) is a useful poor prognostic marker in patients with newly diagnosed acute leukemia, also it can be used as a predictor for complete remission (CR), minimal residual disease (MRD) and survival.
PB1680 SURVIVAL OF ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA (PH NEG) WHO DEVELOP HYPERGLYCEMIA DURING THE INDUCTION OF REMISSION IN AN INTENSIVE CHEMOTHERAPY PROTOCOL IN MEXICO
Authors: Alvarado M. , Rojas F. , Alvarez J. L. , Ortiz M. , Mena V. , de la Peña A. , Espitia M.E. , Perez J. M.
Published: June 2019

Background:

During the induction phase of the treatment exist several factors, besides glycemia control, that predisposed to severe infections like decreased immunity, aplasia of the epithelia, disease activity and chemotoxicity.13 But the effect of hyperglycemia during induction to remission have impact the leukemia‐free survival (LFS) results.

Aims:

The purpose of this study is to determine the incidence of hyperglycemia in therapeutic programs that include

dexamethasone during the induction, and compare leukemia free survival (LFS) and disease‐free survival (DFS) in patients older than 15 years

Methods:

We performed a unicentric, longitudinal, case control study in ALL patients older than 15 years old admitted to the adult hematology Service of the CMN “20 de Noviembre” during the period from 2000 to 2014 treatment with the chemotherapy. Exclusion criteria: history of myelodysplastic syndrome, previous chemotherapy and / or radiotherapy, HIV infection or any condition that precluded their inclusion in chemotherapy (CT) protocols. Patients who abandoned the treatment, who violated the chemotherapy protocol or went to BMT due to high risk disease, were eliminated. Both therapeutic programs (LAL‐6 and LAL‐10) included 4 days of IV dexamethasone (pre‐induction phase) before the start of CT.

Results:

We included 159 patients, 77 women and 82 men; 77 patients presented hyperglycemia during induction phase. The mean follow‐up was 19 months (2 to 61). Hyperglycemia incidence was 51.5%.

The LAL‐6 protocol was received by 56 patients (53% of the group without hyperglycemia and 17% in the hyperglycemia group). The LAL‐10 protocol was used in 102 patients (47% and 83% respectably). The highest elevations occur immediately after concluding the use of dexamethasone, with hyperglycemia in 91 patients and without in 68. This phenomenon maintained until the end of induction and the levels of glucose start to decrease in the following phases (p = 0.0001).

In patients with hyperglycemia at the end of the induction, the average age was 44 years (SD 13) and in those who did not have it was 31 years (SD 12), p = 0. 0001.

Summary/Conclusion:

In the multivariate analysis, the factors that predict the appearance of hyperglycemia, in our experience, were age, female sex, the existence of diabetes and the basal glucose level (> 135 mg / dL). O
PB1699 A SCREENING OF ANTINEOPLASTIC DRUGS FOR ACUTE MYELOID LEUKEMIA REVEALS THAT FLUDARABINE AND CYTARABINE HAVE WEAK CAPACITY AS INDUCERS OF IMMUNOGENIC CELL DEATH
Authors: Ocadlikova D. , Lecciso M. , Redavid A. , Cavo M. , Curti A.
Published: June 2019

Background:

Although antineoplastic drugs used as induction chemotherapy for patients with acute myeloid leukemia (AML) result in high rate of complete remission, disease relapse occurs in the majority of cases, unless stem cell transplant is not performed. Development of new therapies is, then, a major medical need. Among them, strategies harnessing the immune system against leukemia are under active investigation. It is known that the cancer cell death induced by some antineoplastics drugs, such as anthracyclines, is highly immunogenic and results in the maturation of dendritic cells (DCs) and in the efficient cross‐priming of anti‐tumor T cells. This process, named immunogenic cell death (ICD), is characterized by Calreticulin (CRT) and Heat Shock Proteins 70 and 90 (HSP70/90) translocation to cell membrane and release of HMGB1 protein from nucleus.

Aims:

In this study, we were interested in in vitro comparison of five among the most widely used drugs for AML as ICD inducers.

Methods:

HL‐60 AML cell lines were treated with Daunorubicin (DNR), Cytarabine (Ara‐C), Etoposide (VP‐16), Fludarabine (Fluda) and Bortezomib. After apoptosis detection by flow cytometry, traslocation of CRT, HSPs70/90 and HMGB1 release from nucleus were evaluated using flow cytometry and immunofluorescence. Successively, the treated cells were used for loading into healthy donor‐derived DCs which were used to induce T cell proliferation as evaluated by flow cytometry using CFSE.

Results:

All five tested drugs induced a comparable levels of apoptosis. While Bortezomib and VP16 as well as DNR, which is a well‐known ICD inducer, were capable to induce CRT and HSP70/90 traslocation and HMGB1 release from nucleus, Fluda and Ara‐C have low, if any, capacity to induce ICD‐related events. Importantly, only DNR, Bortezomib and VP16 treatment, but not Ara‐C and Fluda, induced DC maturation, thus confirming that ICD‐related events correlate with immunogenic changes in DCs. At the functional level, VP16 was comparable to DNR at eliciting T‐cell proliferation via DCs, whereas Bortezomib, despite its capacity of inducing DC maturation via ICD, had low effect on T‐cell proliferation. Again, Ara‐C and Fluda had no effect on T‐cell proliferation.

Summary/Conclusion:

Our results indicate a novel and poorly‐investigated feature of antineoplastic drugs, commonly used for the treatment of AML, which is based on their different immunogenic potential. Under this viewpoint, Fluda and Ara‐C have weak, if any, capacity as inducers of immunogenic cell death, whereas VP16 and DNR are very effective. Further experiments, addressing the synergistic effects of these different drugs, may help to combine their conventional cytotoxic activity with their immunogenic capacity, thus providing the platform for a novel approach to anti‐leukemia chemotherapy.
PB1713 NEW METHODS FOR ASSESSING THE GENOTOXICITY OF CHEMOTHERAPY DRUGS IN ACUTE MYELOID LEUKEMIA
Authors: Zhogolev D. , Polyakov A. , Kolubaeva S. , Alexander Z. , Noskov Y.
Published: June 2019

Background:

This abstract presents the experience of cultivating the peripheral blast cells of a patient with resistant acute myeloid leukemia (AML) and testing 2 methods for assessing the effects of chemotherapy drugs on them.

Aims:

Suitability examination of cell sorting (CS) and micronucleus test (MT) for assessing the genotoxicity of chemotherapy drugs.

Methods:

Blast cells were obtained by taking blood from a patient with multi‐resistant AML. On sampling days, the percentage of blasts in the patient's peripheral blood ranged from 50% to 75%. In total, 3 in vitro experiments were conducted.

In experiment №1, 520650 CD34+ cells were sorted into 2 tubes, which were incubated for 4 days (37 °C, 5% CO2) in 5 ml of complete nutrient medium (CM): 80% RPMI‐1640, 10% fetal calf serum, 10% of the patient's original serum, 10 μl of phytohaemagglutinin and 100 U/ml penicillin.

After the first day, decitabine was added to one of the samples at a concentration of 1160 ng/ml. To assess the genotoxicity of the drug at the end of cultivation, we determined the number of cells that retained viability by evaluating the results of labeling free DNA.

In experiments №2 and №3, 0.5 ml of blood was cultured with 5 ml of CM. After 24 hours, various concentrations of decitabine (290 ng/ml, 580 ng/ml, 1160 ng/ml) were added to the samples of experiment №2. Daunorubicin (3400 ng/ml) was added to the samples of experiment №3, as well as its combination with interferon alpha‐2a in the calculation of 3600 IU/ml. Next, samples were cultured for 48 hours. To assess the genotoxicity in these experiments MT was used.

Results:

The results of experiment №1 are presented in Figure 1, №2 in table 1, №3 in table 2.

Summary/Conclusion:

1. CS allows selection of the required number of cells with the required phenotype and assess their viability after cultivation with high accuracy. In the sample with the addition of decitabine, living blast cells turned out to be almost 2 times less than in the control sample.

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2. MT can be used to assess the genotoxicity of chemotherapy drugs for peripheral blood blast cells. From the results of experiment №2, it follows that the concentration of the drug has a direct correlation with the level of its genotoxicity on blast cells. In experiment №3, the combination of daunorubicin with interferon showed much stronger genotoxic effects on blast cells compared to daunorubicin without interferon.
PB1727 OUTCOME OF CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA IN ADULT PATIENTS
Authors: El Gammal M. , Mahmoud A. , Samra M. , Elnagar A. , El Shakankiry N.
Published: June 2019

Background:

Core binding factor acute myeloid leukemia (CBF AML) encodes two recurrent cytogentic abnormalities, t(8;21) and inv (16) and carries an overall good prognosis, yet some cases relapse.

Aims:

is to define unfavorable group of CBF AML by analysis of (C‐KIT and FLT3‐ITD) and to correlate with outcome of therapy.

Methods:

Prospective study started at Jan 2015 till June 2017, and included 70 patients CBF AML diagnosed and managed at medical oncology department of National Cancer Institute (NCI), Cairo University. All patients received standard of care protocol at NCI (“3+7”induction followed by 3‐4 courses of high dose cytarabine consolidation. The study was approved by the Institutional Review Board (IRB), of NCI, Egypt.

Results:

the median age was 31 years (18‐60, with a male/female ratio of 4/3. 42(60%) patients had t(8;21) and 28 patients had inversion 16(40%). C‐KIT mutations (exon 8 and exon 17) were detected in 10/52 tested patients and FLT3‐ITD was detected in 3/70 patients. While patients with Inv.16 had more lymphadenopathy and splenomegaly, median initial leucocytic count and exclusive gum hyperplasia, HCV‐Ab positivity (8/42) was exclusively present in patients with t(8;21). Clinically, lymphadenopathy, pallor and dyspnea were associated with worse overall survival (OS)(<0.05). BM cellularity at day 28 of induction had a significant impact on survival (P = 0.002). Median OS was 19.5 month while median disease free survival (DFS) was not reached for the whole group. Patients with Inv.16 had non‐significant better DFS than patients with t(8;21)(P = 0.07). Neither C‐ KIT D816 V mutation nor FLT3‐ITD mutation had significant impact on OS or DFS, but when taken together (either C‐KIT or FLT3‐ITD mutant) had negative impact on DFS (P = 0.04).

Summary/Conclusion:

C‐KIT or FLT3‐ITD mutation had negative effect on DFS but not OS. HCV‐Ab positivity may be associated with t(8;21)AML, while Inv.16 is associated with more extramedullary disease

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PB1743 LIPOSOMAL ANNAMYCIN ‐ A NEW GENERATION ANTHRACYCLINE THAT OVERCOMES MDR AND HAS NO CARDIAC TOXICITY FOR THE TREATMENT OF R/R AML
Authors: Shepard R.
Published: June 2019

Background:

Anthracyclines remain the backbone for induction therapy in the treatment of AML. Unfortunately, most patients will relapse with refractory disease and quickly succumb to their AML. One of the major reasons if not the major reason for developing resistance is the development of MDR. Annamycin was developed and has been shown both preclinically and clinically to overcome MDR and have no cardiac toxicity. Furthermore, it is formulated in a nanomolecular bi‐lamellar liposomal delivery mechanism that targets the leukemic cells in the bone marrow and spares cardiac and other normal cells. Therefore, a new phase I/II clinical trial has been started in both the US and Europe using L‐Annamycin for the treatment of all patients with R/R AML agnostic of mutational status.

Aims:

The aim of the phase I component is to determine the RP2D of L‐Annamycin for the treatment of R/R AML. The phase II component is designed to demonstrate efficacy leading to a phase II registration study for accelerated approval in both the US and EU. PK determinations are being performed for all patients.

Methods:

The phase I component is a standard modified Fibonacci 3+3 design to determine the RP2D. An additional 21 patients will be enrolled as an early determinant of efficacy at the RP2D. The sample size for this is based upon an expected response rate of 15%. Utilizing the optimized Simon two stage design, the assumption is that alpha = 0.1 and beta = 0.2. If less than 1 CR is observed in the first 14 subjects, the study will be stopped for futility. To be declared a success, at least 4 subjects of the 21 needs to demonstrate a CR. A DMC will monitor all data and decide if the study should continue and if any changes to the protocol are needed.

Results:

The study is ongoing in both Europe and the US. The first cohort has completed in the US. Even at the very low starting dose, one of the three patients had a near CR with just MRD after just one three‐day course of L‐Annamycin. The first cohort in Europe has enrolled two patients and updated results will be presented at the EHA Congress.

Summary/Conclusion:

Anthracyclines remain the backbone of induction therapy in AML but most patients will relapse and die from their refractory disease. Resistance develops because of MDR. L‐Annamycin overcomes this and has little to no cardiac toxicity even with up to eight cycles. This study will is designed to demonstrate its efficacy in all patients with R/R AML including the majority with no targetable mutations.

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PB1753 CHIDAMIDE MAY BE EFFECTIVE FOR RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA, ESPECIALLY FOR AML/ETO POSITIVE PATIENTS
Authors: Yao W. , Tong J. , Liu H. , Sun Z.
Published: June 2019

Background:

Epigenetic changes are encountered in acute myeloid leukemia (AML) and are thought to contribute to leukemogenesis. Decreased histone acetylation was frequently found in AML, especially in high‐risk cytogenetics, higher age, secondary or relapsed/refractory AML. HDAC inhibitors have been found to be effective in AML. But the data was limited in China.

Aims:

This retrospective study evaluated the clinical outcomes of chidamide combined with FLAG regimen for relapsed/refractory AML in our single center.

Methods:

From May 2018 to December 2018, 12 patients with relapsed/refractory AML including 6 AML/ETO positive received induction chemotherapy of “chidamide +FLAG” regimen (chidamide 30 mg/d twice a week for two weeks, fludarabine 30 mg/m2/ d for 5 days, Ara‐C 2 g/m2 /d for 5 days, G‐CSF 5‐10ug/kg/d continuedly until neutrophil recoverd).

Results:

A total of 7 patients achieved a complete remission (CR) after induction chemotherapy (CR rate 58.3%). In 6 AML/ETO positive patients, 5 patients achieved molecular remission (CR rate 83.3%). At the end of the follow‐up period, 8 patients underwent hematopoietic stem cell transplantation and 7 patients survived in CR.

Summary/Conclusion:

Chidamide might be suitable drugs in relapsed/refractory AML therapy, especially in AML/ETO positive patients.
PB1754 THE PERIPHERAL CD4+CD8+ T‐CELL LEVEL OF ACUTE LEUKEMIA PATIENTS AFTER HAPLO‐HSCT IS HIGHER THAN THAT OF THESE PATIENTS AFTER HLA‐IDENTICAL‐HSCT
Authors: Li Y. , Dai J. , Huang X.
Published: June 2019

Background:

Nowadays, we generally think that the immune responses after the HLA‐haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) of acute leukemia (AL) patients mainly results from the cross reactivate by donor‐derived memory T‐cells. However, the role of thymus on immune reconstitution after haplo‐HSCT is not clearly understood yet.

Aims:

Regarding the development of CD4‐CD8− (double negative, DN) and CD4+CD8+ (double positive, DP) T‐cell is associated with the function of thymus, we investigate the levels of DN and DP T‐cell in AL patients who have received the haplo‐HSCT or HLA‐identical hematopoietic stem cell transplantation (identical‐HSCT).

Methods:

In the 1st to the 12th months after hematopoietic stem cell transplantation (HSCT), the DN T‐cell and DP T‐cell levels in the peripheral blood of 77 AL patients are evaluated by flow cytometry. And 51 of these patients received haplo‐HSCT, while 26 of them received identical‐HSCT. The repeated measures one‐way ANOVA is used for statistic analysis.

Results:

The DP T‐cell level of AL patients after haplo‐HSCT is significantly higher than those patients after identical‐HSCT (F = 12.02, p = 0.00). however, The DN T‐cell level in these two groups of patients do not show a significantly difference (F = 0.87, p = 0.36). Furthermore, when we only look into the haplo‐HSCT group, we found that the DP T‐cell level of patients donated by the parents (n = 31) is significantly higher than that of the patients donated by the children, (n = 7, F = 6.37, p = 0.03) as well as that of the patients donated by the sister/brother(n = 13, F = 6.64, p = 0.02).

Summary/Conclusion:

From the data of our center, in AL patients after haplo‐HSCT show a high DP T‐cell level than these patients after identical‐HSCT, and this indicates that thymus as the human central immune organ, has a possibility to play a role in immune reconstitution after haplo‐HSCT. But the clinical significance of DP T‐cell on predicting thymus function and immune reconstitution need to be further explored with more patient data. Here, we would like to share our finding on the peripheral DP T‐cell level after haplo‐HSCT, in order to inspire further exploration with other hematologists to clarify the mechanism involve in it.
PB1756 EFFICACY OF SALVAGE CHEMOTHERAPY REGIMENS IN PATIENTS WITH REFRACTORY OR RELAPSED ACUTE MYELOID LEUKEMIA SINGLE CENTER EXPERIENCE
Authors: Simeonova K. , Nikolova V. , Naseva E. , Stoychov M. , Yankova T. , Donchev M. , Arnaudov G. , Balazenkou G. , Guenova M. , Spasov B.
Published: June 2019

Background:

Although understanding in the pathology of AML has developed and a variety of new therapies to AML have been found recently, no response to induction therapy still happens in 20–40% and relapse after CR occurs in 50–70% of the patients, respectively, which are called refractory or relapsed AML (R/R AML) Thus, it is necessary to find effective therapies in treating R/R AML patients.

Aims:

To compare the remission rate and survival between CLARA and FLAG‐Ida salvage chemotherapy in treating patients with refractory or relapsed acute myeloidleukemia (R/R AML).

Methods:

18 R/R AML patients with the following demographic and disease characteristics were treated in our center between 2017‐2018(Table 1.). 7 patients with mean age 46.71 years were treated by CLARA salvage chemotherapy as follows:30 mg/m2/day clofarabine (days 1–5); 1 g/m2/day cytarabine(days 1–5) and 300 mcg/day filgrastim (days 0–till neutrophille recovery). While 11 patients with mean age 50 yeras were treated by FLAG‐Ida: 30 mg/m2/day fludarabine(days 1–5), 2 g/m2/day cytarabine (days 1–5), 8 mg/m2/day idarubicine (days 1–5) and 300 mcg/day filgrastim (days 0–till neutrophille recovery).

Results:

CLARA salvage therapy achieved 57.1 % complete remission rate (CR) and 85.7% overall remission rate (ORR), which was better than FLAG ‐ Ida chemotherapy which realized 36.4% CR and 54.5% ORR. The 30‐day survival rate was higher in CLARA group 85.7% compared to 63.6 in FLAG‐Ida group and it seemed to realize a prolonged OS compared to FLAG – Ida (Table. 3)

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Summary/Conclusion:

In our small group of patients with relapsed/refracoty disease CLARA seemed to be a better tretment option than FLAG ‐ Ida related to both overall response rte and overal survival.
PB1757 MORPHOLOGICAL CHARACTERISTICS, CYTOGENETIC PROFILEAND TREATMENT OUTCOME OF AML1‐ETO POSITIVE ACUTE MYELOID LEUKEMIA; INDIAN PERSPECTIVE.
Authors: S.  , Gupta R. , Gupta A. , Garg A. , Rehman K. , Nityanand S.
Published: June 2019

Background:

Acute myeloid leukemia (AML) is characterized by the proliferation of leukemic myeloid blasts bearing granules and/or Auer rods. Besides acute promyelocytic leukemia, the myeloid blasts in other subtypes of AML have a non‐descript morphology.

Aims:

The aim of this analysis was to determine the morphological features of t (8;21) positive AML and define a score for predicting positivity for this fusion protein in AML.

Methods:

A retrospective analysis of all the cases of AML diagnosed over a period of five years (2013‐2017) at our centre was performed. The clinical and laboratory data of the patients was collected from the patient medical records. The bone marrow aspirate smears were reviewed to define the specific features of t (8;21) positive AML; dyspoiesis in maturing granulocytes, long thin Auer rods, eosinophilia, cytoplasmic vacuoles and presence of Auer rods in maturing myeloid cells.

Results:

A total of 68 cases of t (8;21) positive AML were diagnosed during the study period, with a median age of 19.5 years (range 5‐75 years) with a M:F of 1.7:1. Only twenty percent (14/68) patients belonged to the paediatric age‐group (≤14 years). Granulocytic sarcoma was observed in 10.2% patients at presentation. Morphologically, in accordance to the FAB classification there were 56 AML‐M2, 5 AML‐M1 and 7 AML‐M4 subtypes. Thirteen cases (n = 68) exhibited less than 20% blast in the bone marrow. Characteristic morphological features included presence of dyspoiesis (71%), slender long Auer rods (48%), eosinophilia (19%) cytoplasmic vacuoles in the golgi zone of blasts and maturing myeloid cells (48%). Mast cells, and Auer rods in maturing granulocytic series of cells were seen in a very small fraction of patients, 11% and 3% respectively. 29/68 patients opting for treatment were managed as per the 3+7 protocol. Seventy percent (21/30) achieved CR; there were 5 induction and 8 post induction deaths. With a median follow‐up of 27 months, (range 4‐51 months), the overall survival is 40%. Eleven patients relapsed with a median interval of 7 months, twelve patients‐maintained CR.

Summary/Conclusion:

Since this sub‐group of AML is believed to be a harbinger of good prognosis, recognition of the distinct morphological features of AML1‐ETO AML is essential; it will facilitate a screening for this genetic abnormality. There was no prognostic correlation with any laboratory parameter, however, presence of granulocytic sarcoma in these patients portends a poor prognosis.
PB1773 OVERAL SURVIVAL OF MEXICAN NATIONAL REGISTRY OF ACUTE PROMYEOLOCYTIC LEUKEMIA, AN ANALYSIS OF 324 CASES
Authors: Zapata N. , Montaño E. , Ramos C. , Espinoza R. , Solis J.C. , Barrera E. , Mijangos J. , Diaz G. , Solís R. , Perez O. , Herrera M. , Gomez D. , Cabrera A. , Flores J.A. , Solano M. , Guillermo V. , Ceballos A. , Ojeda J. , Gomez G. , Lyn L. , Mena V. , De la Peña J.A. , Ortiz M. , Perez J. , Espitia M.E. , Alvarez J.L. , Aguilar M. , Alvarado M.
Published: June 2019

Background:

Acute Promyelocytic Leukemia is a myeloid dissease wich is informed to be more frequent in latinos, but there is few epidemiological data about these.

This is a review of 19 Hospitals in different states of Mexico, from Northern to South of Mexico.

A retrospective study of all cases of acute promyelocytic leukemia treated from 2007‐2018, a total of 324 cases.

Aims:

Our Aim objective is to know our overall survival of the population with acute promyelocyic leukemia treated in different institutions in Mexico

Secondary objectives: Learn about treatment used in theses different institutions, and mortality related.

Methods:

We perform a rtrospective analysis from 2007‐2018, a total of 324 cases diagnose with acute promylocytic leukemia, inform consent was perform in all cases

Results:

The Median age 36 years old (range 15‐73), relation male:female 163:161. Infection at diagnosis 12%(39cases), DIC 31% (102 cases), Hemorrages 21%, CNS:8cases, Gastrointestinal 18cases, urinary tract:15, skin:28 cases. Leucocite at diagnosis median of 22.3 (1.0‐450), Platelets median of 40 (2‐318), Fybrogen median 190 range22‐825, TTPa 32 seconds (28‐255).

Risk at diagnosis: low 36%, intermediate:24%, high risk:40%. ATRA used in 94% of the cases and antracyclines used Daunorrubicin 58%, and Idarrubicin 42%. Mortality of 14%. ATRA syndrome 16% in the Daunorrubicin arm and 20% idarrubicin

Summary/Conclusion:

We show that patient treated with daunorrubicin had a better survival during the induction, with a overall mortality of 14% in the induction related mortality.

Median age of diagnosis 36 years old.

In Mexico there is no ATO, so we still treating patients with chemotherapy and a maintenance of 2 years afther 3 consolidations, the most used atracycline is daunorrubicin. There was no difference between the ATRA syndrome in both antracyclines.
PB1797 DEATHS IN PEDIATRIC BURKITT LYMPHOMA PATIENTS. WHAT COULD BE IMPROVED?
Authors: Abdelrahman H. , Hamoda A. , El Kenaai N. , Salem S. , Zaki I. , Taha G. , Ahmed O.
Published: June 2019

Background:

Many patients with Burkitt lymphoma has rapid tumor regression following administration of chemotherapeutic drugs. However, while the patients are making “good progress” clinically, some of them suddenly collapse and die.

Aims:

The aim of this work is to analyze causes of death among pediatric mature B cell NHL, to identify adverse prognostic factors that might put those patients at high risk of mortality at different phases of treatment. And finally, to set a series of recommendation to ameliorate the OS and avoid unexpected treatment related mortality

Methods:

We conducted a retrospective analysis that included all Burkitt Lymphoma (BL) patients who were diagnosed and treated at CCHE during the period from 06/2012 till end of 12/2018 and died. All patients were treated according to LMB96 protocol, and were stratified as low, intermediate or high risk group. Analysis included epidemiologic data, initial presentation, laboratory and radiologic investigations, tumor stage, risk stratification, direct cause of death, associated co‐morbidity and phase of treatment where death occurred.

Results:

Out of 570 patients recorded during the study period, 84 (14.7%) died. Majority (69%) were males with mean age 7.6 years. Most of them (94%) had advanced stage (III and IV) disease. Forty eight patients from intermediate (12.2%), and 36 from high risk group (28.3%) died. Majority of patients (78.6%) died in active disease, while 21.4% died in CR/PR. Main causes of death were septic shock (34.5%), disease progression in (31%), tumor lysis syndrome (TLS) (11.9%). Other reported causes of death were sever chest infection (6%), multi‐organ failure associated with sepsis (6%), pulmonary hemorrhage (2.4%), neutropenic enterocolitis, GVHD, and gut perforation (1.2%) each. Three patients (3.6%) died upon arrival to the hospital without receiving any kind of chemotherapy, 17 (20.4%) during prephase, 24 (28.5%) during induction, 8 (9.5%) during consolidation, 2 (6.1%) during maintenance phase. For relapsing patients, 18 (21.4%) died from chemotherapy toxicity of second line, while 6 (7.1%) were on palliative care when they died.

Summary/Conclusion:

Despite being a well‐equipped tertiary care hospital dedicated to the management of pediatric malignancies, we report a very high mortality rate in our hospital. Late presentation, TLS and sever sepsis are main causes of death throughout different phases of treatment. For relapsed patient, toxicity of 2nd line chemotherapy and tumor progression are the main causes of death. We need intensify supportive care measures, and to better identify patients at high risk for mortality to avoid unnecessary patients’ death.
PB1804 OUTCOME OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN FIRST COMPLETE REMISSION IN PATIENTS WITH LOW‐RISK PERIPHERAL T‐CELL LYMPHOMAS (PTCLS)
Authors: Huang H. , Liu S. , Chen X. , Jin Z. , Wu D.
Published: June 2019

Background:

Patients with peripheral T cell lymphomas (PTCLs) generally have a poor prognosis with conventional chemotherapy. Consolidation with autologous stem cell transplantation is an option for patients with PTCL. However, whether prospective or retrospective studies on the timing of autologous stem cell transplantation remains controversial. We cannot determine whether autologous stem cell transplantation is necessary in patients with PTCL achieving first complete remission (CR1) following induction chemotherapy, especially in patients with low‐risk group. Therefore, we compare prognosis of low‐risk patients who underwent ASCT in CR1 following induction regimens and patients who underwent observation and waiting during CR1.

Aims:

We compare progression‐free survival of low‐risk patients who underwent ASCT in CR1 following induction regimens and patients who underwent observation and waiting during CR1.

Methods:

We completed a retrospective analysis for low‐risk PTCL patients who underwent either observation or up‐front ASCT during CR1 in our center between 1/1/2007 and 12/31/2018. In our study, patients with PTCL age ≤65 years(median age, 52 years) and IPI score 0‐1 were included. Histologic subtypes include PTCL not otherwise specified (PTCL‐NOS), angioimmunoblastic T‐cell lymphoma a(AITL) and anaplastic lymphoma kinase‐negative large cell lymphoma (ALK‐negative ALCL). In addition, patients with cutaneous T cell lymphoma and anaplastic lymphoma kinase‐positive large cell lymphoma (ALK‐positive ALCL) were excluded. The probabilities of PFS was calculated by the Kaplan‐Meier method and compared by a log‐rank test. The estimated lymphoma of relapse was calculated using cumulative incidence.

Results:

In our center, 42 patients met all inclusion and exclusion criteria. And 29 patients underwent observation and waiting in CR1, 13 patients underwent consolidative ASCT. In low‐risk patients of PTCL, with a median follow‐up of 22 months, estimated 2‐year PFS and 5‐year PFS in the observation group were 57.4% and 46.0%, respectively. Among ASCT recipients, the 2‐year and 5‐year PFS were 67.7% and 54.2%, respectively. When considering incidence of disease relapse, the 1‐year cumulative incidence of relapse in the observation and ASCT groups was 20.3% and 32.3%, respectively. However, there were no difference between observation and ASCT groups.

Summary/Conclusion:

In conclusion, for low‐risk PTCL patients achieving CR1 following induction therapy, consolidative ASCT does not extend progression‐free survival compared to observation. We favor proceeding to observe and wait because of high toxic of hematopoietic stem cell transplantation.

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PB1811 A SINGLE ARM MULTICENTENNIAL CLINICAL STUDY IN THE TREATMENT OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA(PCNSL) WITH ALTERNATIVE CHEMOTHERAPY SEQUENT WITH AUTOLOGOUS TRANSPLANTATION
Authors: zhou S. , Li J. , Wen Q. , Wang S. , Lou S. , Yang T. , Li B. , Liu X. , Han X. , Gao L. , Zhang C. , Kong P. , Gao L. , Liu Y. , Zhang X.
Published: June 2019

Background:

Primary central nervous system lymphoma(PCNSL)is a highly aggressive form of lymphoma with poor clinical outcomes and lack of a standard treatment regimen.

Aims:

To explore the methods of treatment in PCNSL.

Methods:

Patients aged 18‐60 years with newly diagnosised PCNSL are treated with MTX+CDOD (Cyclophosphamide 750 mg/m2 d1, Doxorubicin HCl 40 mg/m2 d1, Vindesine 4 mg d1, dexamethasone 10 mg d1‐5, MTX 3 g/m2 d2) /MTX+HD‐Ara‐C (cytarabine 1.5 g/m2 q12 h d1‐2, methotrexate 3 g/m2 d3) Alternative chemotherapy for 6 total cycles, whose response evaluation is more than partial remission(PR) then sequentially with ASCT.

Results:

From June 2017 to June 2018, 17 patients in five hospitals in southwest China accepted CDOD+MTX/HD‐Ara‐C+MTX Alternative chemotherapy sequent with ASCT. The median age was 46(32‐57), 9 males and 8 females, among the pathological types, 1 patient was high‐grade B‐cell lymphoma, and the rest were DLBCL. Two patients dropped out of the study at course 4 and 5 of chemotherapy for disease progression, the remaining 15 patients received ASCT sequentially. Before transplantation, 12 patients reached complete remission(CR), 3 patients reached PR. The overall remission rate of chemotherapy is 88%. After transplantation, 13 patients CR, 2 patients still PR. By January 2019, the median follow‐up time was 9 months(7‐12), two patients relapsed and one patient died after recurrence, the median overall survival(OS) is 9months9(7‐12), and the median progression free survival(PFS) is also 9 months9(6‐12). No grade III/IV hematological or non‐hematological adverse events were observed.

Summary/Conclusion:

Our preliminary results show that RCDOD+MTX/HD‐Ara‐C+MTX alternative chemotherapy sequent with ASCT is a effective and safe trentment for PCNSL, and long‐term follow‐up is needed to further evaluate its efficacy.
PB1822 HIV‐ASSOCIATED LYMPHOMA: A REPORT OF 40 CASES AT YOPOUGON TEACHING HOSPITAL IN CÔTE D’IVOIRE
Authors: Kouakou B. , Diakité M. , Silué A.D. , Packo D.L.V.S.C. , Atiméré Y.N. , N’dhatz‐Comoé E. , Kamara I. , Chefou E.H.M. , Botti R.‐P. , Danho N.C. , Tolo‐Dièbkilé A. , Koffi G.K. , Sanogo I.
Published: June 2019

Background:

Lymphomas are a heterogeneous group of malignant haemopathies characterized by ganglionic and extra ganglionic infiltration of lymphoid cells. Their occurrence during the HIV infection had a specific clinical, therapeutic and evolutionary particularities.

Aims:

The aims of our study was to evaluate and compare the clinical, therapeutic and evolutionary aspects of HIV and none HIV patients.

Methods:

It was a descriptive and analytical case‐control study of patients with lymphoma followed at the department of clinical hematology at Yopougon Teaching Hospital from January 2014 to October 2016. The histology and immunohistochemistry was the diagnosis’ means to retain the diagnostic of lymphoma. The HIV test was performed by Western Blood. The variables of our study were the epidemiological, clinical, therapeutic and evolutionary aspects. Statistical analyzes were performed with épi info 351 and SPSS. The statistical test used was the ki2 test.

Results:

We collected 40 cases of lymphoma including 15 cases of HIV positive and 25 cases negative. The average age was 47 years with extremes of 27 and 65 years old. There was more male than female with a sex ratio of 2 for HIV positive and 3.16 for HIV negative. The reasons of consultation were dominated by polyadenopathies. The WHO performans status was stage 2 for 53.33% of HIV‐positive patient and stage 1 for 68% of HIV‐negative patients. Among HIV‐positive patients, 60% knew their status before the discovery of lymphoma and 53% already had opportunistic infections dominated by digestive and genital candida infection in 50% of cases. We noted 80% of aggressive lymphoma in the HIV‐positive patients with 26.6% Burkitt's lymphoma versus 68% aggressive lymphoma in the HIV‐negative patient. The lymph node localization was the most common with 66.6% for HIV‐positive patients and 84% for HIV‐negative patients. The breast localization was particularity observed with HIV positive patient. 86.6% of HIV‐positive patients have a bad prognosis against 16% for the HIV‐negative patients. For the treatment, the CHOP 21 protocol was the most used in both groups with 66.8% for HIV‐positive patients and 60% for HIV‐negative patients. The compliance was poor at 77% with HIV‐positive patients. The Median survival was 33 and 11 months, respectively, in the HIV‐negative and HIV‐positive patients.

Summary/Conclusion:

The prognosis of lymphoma with HIV remains pejorative in our country because often unknown before the diagnosis of lymphoma.
PB1823 PROGNOSTIC FACTORS AND TREATMENT OUTCOME OF RELAPSING AND REFRACTORY MATURE B CELL NON HODGKIN LYMPHOMA CCHE EXPERIENCE
Authors: Hamoda A. , Abdelrahman H. , Fathy el semary S. , El Kinaai N. , Zaki I. , Salem S. , Naggy N. , Ahmed O.
Published: June 2019

Background:

Treatment of non‐Hodgkin lymphoma (NHL) is an example of successful therapy of cancer in children with a cure rate approximating 80%. Unfortunately, relapsed NHL has a dismal outcome, and customary treatment is by highly toxic chemotherapy followed by hematopoietic stem cell transplantation (HSCT).

Aims:

To analyze prognostic factors, and to report treatment outcome of relapsing/refractory mature B cell NHL.

Methods:

A retrospective analysis including all patients less than 18 years initially diagnosed as mature B cell NHL who were primary refractory to chemotherapy or relapsed during the period between July 2012 till end of 2017 at the Children Cancer Hospital Egypt (CCHE).

Results:

Out of 494 patients diagnosed during the study period, 34 (7%) were included in our study. Twenty‐three (67.6%) had Burrkitt lymphoma, while 5 (14.7%) had diffuse large B cell lymphoma. The majority were males (79.4%), with a median age 6.2 years. According to Modified Murphy Staging, 6 patients (17.6%) were stage II, 24 (70.6%) stage III, and 4 (11.8%) stage IV. Bone marrow (BM) involvement at presentation was detected in 2 patient, and 3 (8.8%) had CNS infiltration. Thirty patients (88.2%) received LMB protocol, and 4 (11.8%) R‐CHOP as primary chemotherapy. One patient (2.9%) was treated as low risk, 28 (82.4%) as intermediate, and 5 (14.7%) high risk. Median delay in 1st line treatment was 22 days (range 0 to 162).Twenty two patients (64.7%) relapsed, and 12 (35.3%) had tumor progression. Relapse was early in 15 (68.2%), and late in 7 patients (31.8%). It was documented by tissue biopsy in 30 patients (88.2%), and bone marrow aspirate in 3 (8.8%). Patients relapsed other than primary site were 6/34 (17.6%). CNS relapse was detected in 8 (23.5%), BM in 8 (20.5%), while combined BM and CNS in 2 (5.9%). R‐ICE was the 2nd line of treatment in 29 patients (85.3%), and complete 2nd remission (CR) was achieved in 7 patients (20.6%). Allogeneic HSCT was done for 2 patients (5.9%), and autologous HSCT for 3 patients (8.8%). Finally, 7/34 (20.5%) patients were alive in CR, and 24/37 (70.5%) died. The 3 years Overall survival (OS) 35.3%, with no statistical difference between relapsing and progression. The 3 years OS for patient who underwent HSCT was 80% compared 20% for no HSCT (p = 0.034).

Summary/Conclusion:

Our relapse rate is higher than the literature probably due to delay of chemotherapy with loss of dose intensity. For patients in second remission, HSCT markedly improves the outcome.
PB1824 MARITAL STATUS AS A PROGNOSTIC FACTOR IN DIFFUSE LARGE B‐CELL LYMPHOMA, SEER DATA BASED STUDY
Authors: Ahmed M. , Pandu A. , Darwish T. , Mostafa N.
Published: June 2019

Background:

Studies showed that marital status has an impact on the survival of patients with different types of cancers. There's no study, up to our knowldge, that discussed the prognostic impact of marital status on the outcome of Diffuse Large B‐cell Lymphoma (DLBCL) Patients.

Aims:

To assess the impact of marital status on the outcome of patients with DLBCL before and after the addition of Rituximab to the treatment.

Methods:

We reviewed the Surveillance, Epidemiology, and End Results (SEER) registry and compared survival trends among DLBCL patients from 1973 to 2015. Patients were classified according to their marital status into 3 gropus; Group I (married), group II (Single) and group III (Widowed/Divored/separated)

Results:

We identified 118293 patients above the age 19 years, (54% males, 85% white, 62% are 60+ years), staging information was available for 90% of cases, were distributed between early stage (I/II) and advanced stage (III/IV) (45% each).

Fifty Eight percent of patients were in group I, 16% in gruop II and 26% in group 3. After excluding patients with missed data it was found that group III are significantly associated with older age (>60 years) and female sex compared to group I and group II with p‐value 0.00 each.

Median overall survival time (OS) in pre‐Rituximab era (Diagnosed 1997 or before) was 29 Months compared to 213 Months in post‐Rituximab era (after 1997). Before introduction of Rituximab There was statically significant difference in the OS of Married group (50 Months) compared to Single (15 months)and widowed/divorced/separated group (17 months), P Value 0.00. After 1997, Married & single patients were associated with better outcome with Median OS of (227 Months) compared to (63 months) in the widowed/divorced/separated group, p‐value 0.00.

Summary/Conclusion:

Marital status has a prognostic significance on the outcome of DLBCL. Widowed/divorced/separated group had worse prognosis than married group, this group may need more social support to improve their outcome.