- Email: [email protected]
Refractory Acute Lymphoblastic Leukemia
Abstracts ALL-224
ALL-226
Evaluation of CD 25 (IL2 Receptor Alpha) Expression in Adult Acute Lymphoblastic Leukemia Patients
MTHFR C677T Polymorphism Screening: A Challenge in Acute Lymphoblastic Leukemia
Rasha Magdy Mohammed Said ,3 Inas Ahmed Asfour,1 Gihan Mohamed Kamal Shams El Din,2 Entessar Mabrook Juadam4
Rim Frikha Tarek Rebai
1
Context: Genotyping of MTHFR polymorphism is a challenge for personalized medicine in acute lymphoblastic leukemia(ALL). Objective: To assess the prevalence of MTHFR polymorphism, mainly the C677T in a cohort of patients with acute lymphoblastic leukemia. Design: A retrospective study. Setting: university hospital. Patients or Other Participants: 35 patients with acute lymphoblastic leukemia who attended the hematology department. Interventions: clinical; biological and therapeutic data were recorded. Main Outcomes Measures: Genomic DNA was extracted from EDTA-anticoagulant blood samples according to salting protocol. Genotyping of the C677T of MTHFR was performed by PCR RFLP using the HinfI. Results: The frequency of the MTHFR 677C>T was 22.8% among the ALL patients with a particularly history of relapse and toxicity during methotrexate treatment. Conclusions: Despite the limit of this study (size and duration), our finding highlights the impact of the c677T variant of MTHFR on leukemogenesis. Thus, genotyping of MTHFR polymorphism, the C677T, is mandatory to personalize therapy and reduce methotrexate toxicity in ALL.
Professor of Internal Medicine and Clinical Hematology, Faculty of
Medicine - Ain Shams University, Cairo, Egypt; 2Assistant Professor of Internal Medicine and Clinical Hematology, Faculty of Medicine Ain Shams University, Cairo, Egypt; 3Lecturer of Internal Medicine and Clinical Hematology, Faculty of Medicine - Ain Shams University, Cairo, Egypt; 4Sabratha Oncology Center-Libya, Sabratha, Libya
Background: Acute lymphoblastic leukemia (ALL) in which 8085% of ALL are of B-cell lineage (B-cell precursor ALL), and 1520% are of T-cell lineage (T-ALL) .The IL-2 Receptor (IL-2R) a subunit has low affinity for its ligand but has the ability (when bound to the b and Y subunit) to increase the IL-2R affinity 100fold. Heterodimerization of the b and Y subunits of IL-2R is essential for the signalling in T cells. Our study performed a detailed assessment of the clinical implications and the prognostic value of the CD25. Patients and Methods: It was conducted on 30 adults patients recruited from inpatient and outpatient departments in Ain Shams university, newly diagnosed as ALL with ages above 18 years old, during 2015 and 2016.Immunophenotyping was performed on fresh cells according to standard protocol for ALL in addition CD25 marker was assessed for all patients using Coulter EPICSXL.7Mononuclear cell fractions were isolated from heparinized bone marrow or peripheral blood samples by FicolleHypaque density gradient centrifugation .PCR and Fluorescence in situ hybridization (FISH) for BCR e ABLI fusion gene were also performed . Results: In our study 13 (43. 33%) patients with ALL had positive CD25. We showed that CD25 measurements compare favorably with other ALL prognostic criteria. This is an important finding because the CD25 assay is a robust assay that is simple to perform, widely available, has a well established inter-laboratory reference range and is relatively inexpensive. In our study (70%) patients were males while (30%) were females with no significant difference as correlated with CD25. Also recurrent infections had occurred in 8 patients (26. 67%) with no significant correlation with CD 25 (P ¼ 0. 361), 16 (53. 33%) patients suffered from fever, while 5 (16. 67%) experienced bleeding with no significant correlation of them with CD 25 (P> 0. 05 in both). FISH cytology and PCR were positive in 11 (36. 67%) patients. CD25 is found to be an independent prognostic factor in patients with ALL. There was a significant correlation between CD 25 and FISH and PCR for BCR-BLI, LDH, total leucocytic count (P value <0.05). Conclusion: (CD25) expression was corresponding to Philadelphia chromosome and it differed according to the acute leukemia subgroups. IL-2R a (CD25) might be a valuable marker for monitoring ALL after chemotherapy. It represents highly important parameter for prognosis and follow-up of ALL patients.
Laboratory of Histology; Faculty of Medicine of Sfax; Tunisia, Sfax, Tunisia
ALL-237 Use of Bortezomib in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia Adriana Bello ,1 Rossana Cortez,2 Maylu Collazo2 1
Hospital Dr Carlos Arvelo, Caracas, Venezuela; 2Ciudad Hospitalaria
Dr Enrique Tejera, Valencia, Venezuela
Context: Treating relapsed /refractory pediatric acute lymphoblastic leukemia (ALL), in developing countries, is a challenge. Novel options with reasonable efficacy /toxicity profile are needed. Objective: To determine whether a Bortezomib containing regimen, is efficacious in achieving complete remissions, in pediatric patients with relapsed /refractory ALL, in low resource setting. Design /Setting: We retrospectively evaluated a cohort patients, with relapsed /refractory ALL, who received Bortezomib with chemotherapy, from 2013 to 2016, at two referral centers under the supervision of this study’s authors. Patients: 15 pediatric patients, aged 2 to 15, affected B-cell precursor or T cell ALL, either from our institutions or referred, were given Bortezomib with standard chemotherapy. Bone marrow (BM) blast percentage was above 25%, before treatment. Relapse was either hematological, or combined. Early or late relapse, as well as primary resistant.
Clinical Lymphoma, Myeloma & Leukemia September 2017
- S269
Abstracts Table 1 Characteristics of Patients
End of induction Number MRD Response Complic relapse Initial risk
Lines of treatment pre Bort comb
A
G
Type
Relapse
Perform score (ECOG)
3
M
B
early
0
BM
1
low
positive
CR
F/N
1
4 2
M M
T ETP
early early
0 0
CNS + BM CNS+BM
1 1
high high
neg positive
CR Resistant
F/N TLS
1 1
3 4
M M
B B
early early
0 0
BM CNS+BM
1 1
low low
neg neg
Resistant CR
F/N none
1 1
13 15
M F
B T
resist late
0 0
BM CNS+BM
2
high high
pos neg
Resistant Partial
death death
1 3
5 13
M M
B T
late early
0 0
Test+BM CNS+BM
1 1
low high
neg neg
CR Resist
none F/N
1 2
9 15
F F
B B
early resist
0 0
BM BM
1
low high
neg positive
CR Partial
none death
2 1
10 15
M M
B B
late early
0 0
Test+BM BM
2 1
high high
neg pos
CR Resistant
none F/N
2 2
5 12
M M
B B
early late
0 0
BM CNS+BM
2 2
low high
neg neg
Resistant Partial
F/N death
3 2
Site
Had received BMT Had t(1;19)
Number of relapses, previous treatments, including bone marrow transplantation (BMT), initial features and molecular studies were summarized in the table 1. Intervention: Bortezomib 1.3mg/m2 intravenously on days 1, 4, 8 and 11. Dexamethasone 20mg/m2/d during10 days, vincristine 4 doses, Peg-asparaginase on days 2 and 15 (or E. Coli or Erwinia), mitoxantrone 10mg/m2 days 1 and 8, and 4 triple intrathecals, were given as per Children’s Oncology Group protocol COG-ALL07P1. Prophylactic broad spectrum antibiotics and antifungal were provided to all patients. Main Outcome Measure: Complete remission (CR) was assessed at day 29, was defined as a recovered marrow, with less than 5% blasts by bone marrow morphology, as well as minimal residual disease (MRD) less 0.1%. Results: Complete remission was achieved in 6/15 patients (40%). Three patients died before finishing the protocol, from febrile neutropenia (FN). 1 patient with early T progenitors (ETP) ALL died from tumor lysis syndrome (TLS), and another with t(1;19) had severe spinal compromise, and died from central nervous system (CNS) infection. Six patients were refractory. Conclusions: Bortezomib with chemotherapy is feasible, tolerated and efficacious in low resource setting as salvage for relapsed /refractory pediatric acute lymphoblastic leukemia.
S270
-
Clinical Lymphoma, Myeloma & Leukemia September 2017
Acute Myeloid Leukemia
AML-003 Extra Medullary Relapse post Allogenic Stem Cell Transplantation Tends to Occur Late, Patients have a Better Chance of Receiving a Second Transplant with Better Outcomes Mona Hassanein , Ghada Elgohary, Noura Alhashim, Maamoun Alsermani, Muhned Alhumaid, Syed Osman Ahmed, Feras Alfraih, Mahmoud Aljurf, Fahad Almohareb, Fahad Alsharif, Hazzaa Alzahrani, Naeem Chaudhri, Amr Hanbali, Shahrukh Hashmi, Mohamed Said, Waleed Rasheed, Marwan Shaheen, Riad Elfakih King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Context: Acute myeloid leukemia (AML) relapse after Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) remains a significant cause of mortality and morbidity. Bone marrow Relapse is the most frequent presentation. Extra Medullary Relapse (EMR) is less common, the incidence of EMR in the literature ranges from 0.65% up to 41%. Objective: To study the characteristics, outcomes and risk Factors of EMR post Allo-HSCT for adult AML, and to compare with Isolated Medullary Relapse (IMR). Design: Retrospective Study included AML patients, who underwent AlloHSCT from January 2005 to December 2015. Setting: Single institution study from King Faisal specialist hospital and Research Center, Riyadh, KSA. Patients: A total of 268 patients, 95 experienced disease relapse, 59 had IMR and 36 had EMR with or
ALL-226
Evaluation of CD 25 (IL2 Receptor Alpha) Expression in Adult Acute Lymphoblastic Leukemia Patients
MTHFR C677T Polymorphism Screening: A Challenge in Acute Lymphoblastic Leukemia
Rasha Magdy Mohammed Said ,3 Inas Ahmed Asfour,1 Gihan Mohamed Kamal Shams El Din,2 Entessar Mabrook Juadam4
Rim Frikha Tarek Rebai
1
Context: Genotyping of MTHFR polymorphism is a challenge for personalized medicine in acute lymphoblastic leukemia(ALL). Objective: To assess the prevalence of MTHFR polymorphism, mainly the C677T in a cohort of patients with acute lymphoblastic leukemia. Design: A retrospective study. Setting: university hospital. Patients or Other Participants: 35 patients with acute lymphoblastic leukemia who attended the hematology department. Interventions: clinical; biological and therapeutic data were recorded. Main Outcomes Measures: Genomic DNA was extracted from EDTA-anticoagulant blood samples according to salting protocol. Genotyping of the C677T of MTHFR was performed by PCR RFLP using the HinfI. Results: The frequency of the MTHFR 677C>T was 22.8% among the ALL patients with a particularly history of relapse and toxicity during methotrexate treatment. Conclusions: Despite the limit of this study (size and duration), our finding highlights the impact of the c677T variant of MTHFR on leukemogenesis. Thus, genotyping of MTHFR polymorphism, the C677T, is mandatory to personalize therapy and reduce methotrexate toxicity in ALL.
Professor of Internal Medicine and Clinical Hematology, Faculty of
Medicine - Ain Shams University, Cairo, Egypt; 2Assistant Professor of Internal Medicine and Clinical Hematology, Faculty of Medicine Ain Shams University, Cairo, Egypt; 3Lecturer of Internal Medicine and Clinical Hematology, Faculty of Medicine - Ain Shams University, Cairo, Egypt; 4Sabratha Oncology Center-Libya, Sabratha, Libya
Background: Acute lymphoblastic leukemia (ALL) in which 8085% of ALL are of B-cell lineage (B-cell precursor ALL), and 1520% are of T-cell lineage (T-ALL) .The IL-2 Receptor (IL-2R) a subunit has low affinity for its ligand but has the ability (when bound to the b and Y subunit) to increase the IL-2R affinity 100fold. Heterodimerization of the b and Y subunits of IL-2R is essential for the signalling in T cells. Our study performed a detailed assessment of the clinical implications and the prognostic value of the CD25. Patients and Methods: It was conducted on 30 adults patients recruited from inpatient and outpatient departments in Ain Shams university, newly diagnosed as ALL with ages above 18 years old, during 2015 and 2016.Immunophenotyping was performed on fresh cells according to standard protocol for ALL in addition CD25 marker was assessed for all patients using Coulter EPICSXL.7Mononuclear cell fractions were isolated from heparinized bone marrow or peripheral blood samples by FicolleHypaque density gradient centrifugation .PCR and Fluorescence in situ hybridization (FISH) for BCR e ABLI fusion gene were also performed . Results: In our study 13 (43. 33%) patients with ALL had positive CD25. We showed that CD25 measurements compare favorably with other ALL prognostic criteria. This is an important finding because the CD25 assay is a robust assay that is simple to perform, widely available, has a well established inter-laboratory reference range and is relatively inexpensive. In our study (70%) patients were males while (30%) were females with no significant difference as correlated with CD25. Also recurrent infections had occurred in 8 patients (26. 67%) with no significant correlation with CD 25 (P ¼ 0. 361), 16 (53. 33%) patients suffered from fever, while 5 (16. 67%) experienced bleeding with no significant correlation of them with CD 25 (P> 0. 05 in both). FISH cytology and PCR were positive in 11 (36. 67%) patients. CD25 is found to be an independent prognostic factor in patients with ALL. There was a significant correlation between CD 25 and FISH and PCR for BCR-BLI, LDH, total leucocytic count (P value <0.05). Conclusion: (CD25) expression was corresponding to Philadelphia chromosome and it differed according to the acute leukemia subgroups. IL-2R a (CD25) might be a valuable marker for monitoring ALL after chemotherapy. It represents highly important parameter for prognosis and follow-up of ALL patients.
Laboratory of Histology; Faculty of Medicine of Sfax; Tunisia, Sfax, Tunisia
ALL-237 Use of Bortezomib in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia Adriana Bello ,1 Rossana Cortez,2 Maylu Collazo2 1
Hospital Dr Carlos Arvelo, Caracas, Venezuela; 2Ciudad Hospitalaria
Dr Enrique Tejera, Valencia, Venezuela
Context: Treating relapsed /refractory pediatric acute lymphoblastic leukemia (ALL), in developing countries, is a challenge. Novel options with reasonable efficacy /toxicity profile are needed. Objective: To determine whether a Bortezomib containing regimen, is efficacious in achieving complete remissions, in pediatric patients with relapsed /refractory ALL, in low resource setting. Design /Setting: We retrospectively evaluated a cohort patients, with relapsed /refractory ALL, who received Bortezomib with chemotherapy, from 2013 to 2016, at two referral centers under the supervision of this study’s authors. Patients: 15 pediatric patients, aged 2 to 15, affected B-cell precursor or T cell ALL, either from our institutions or referred, were given Bortezomib with standard chemotherapy. Bone marrow (BM) blast percentage was above 25%, before treatment. Relapse was either hematological, or combined. Early or late relapse, as well as primary resistant.
Clinical Lymphoma, Myeloma & Leukemia September 2017
- S269
Abstracts Table 1 Characteristics of Patients
End of induction Number MRD Response Complic relapse Initial risk
Lines of treatment pre Bort comb
A
G
Type
Relapse
Perform score (ECOG)
3
M
B
early
0
BM
1
low
positive
CR
F/N
1
4 2
M M
T ETP
early early
0 0
CNS + BM CNS+BM
1 1
high high
neg positive
CR Resistant
F/N TLS
1 1
3 4
M M
B B
early early
0 0
BM CNS+BM
1 1
low low
neg neg
Resistant CR
F/N none
1 1
13 15
M F
B T
resist late
0 0
BM CNS+BM
2
high high
pos neg
Resistant Partial
death death
1 3
5 13
M M
B T
late early
0 0
Test+BM CNS+BM
1 1
low high
neg neg
CR Resist
none F/N
1 2
9 15
F F
B B
early resist
0 0
BM BM
1
low high
neg positive
CR Partial
none death
2 1
10 15
M M
B B
late early
0 0
Test+BM BM
2 1
high high
neg pos
CR Resistant
none F/N
2 2
5 12
M M
B B
early late
0 0
BM CNS+BM
2 2
low high
neg neg
Resistant Partial
F/N death
3 2
Site
Had received BMT Had t(1;19)
Number of relapses, previous treatments, including bone marrow transplantation (BMT), initial features and molecular studies were summarized in the table 1. Intervention: Bortezomib 1.3mg/m2 intravenously on days 1, 4, 8 and 11. Dexamethasone 20mg/m2/d during10 days, vincristine 4 doses, Peg-asparaginase on days 2 and 15 (or E. Coli or Erwinia), mitoxantrone 10mg/m2 days 1 and 8, and 4 triple intrathecals, were given as per Children’s Oncology Group protocol COG-ALL07P1. Prophylactic broad spectrum antibiotics and antifungal were provided to all patients. Main Outcome Measure: Complete remission (CR) was assessed at day 29, was defined as a recovered marrow, with less than 5% blasts by bone marrow morphology, as well as minimal residual disease (MRD) less 0.1%. Results: Complete remission was achieved in 6/15 patients (40%). Three patients died before finishing the protocol, from febrile neutropenia (FN). 1 patient with early T progenitors (ETP) ALL died from tumor lysis syndrome (TLS), and another with t(1;19) had severe spinal compromise, and died from central nervous system (CNS) infection. Six patients were refractory. Conclusions: Bortezomib with chemotherapy is feasible, tolerated and efficacious in low resource setting as salvage for relapsed /refractory pediatric acute lymphoblastic leukemia.
S270
-
Clinical Lymphoma, Myeloma & Leukemia September 2017
Acute Myeloid Leukemia
AML-003 Extra Medullary Relapse post Allogenic Stem Cell Transplantation Tends to Occur Late, Patients have a Better Chance of Receiving a Second Transplant with Better Outcomes Mona Hassanein , Ghada Elgohary, Noura Alhashim, Maamoun Alsermani, Muhned Alhumaid, Syed Osman Ahmed, Feras Alfraih, Mahmoud Aljurf, Fahad Almohareb, Fahad Alsharif, Hazzaa Alzahrani, Naeem Chaudhri, Amr Hanbali, Shahrukh Hashmi, Mohamed Said, Waleed Rasheed, Marwan Shaheen, Riad Elfakih King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
Context: Acute myeloid leukemia (AML) relapse after Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) remains a significant cause of mortality and morbidity. Bone marrow Relapse is the most frequent presentation. Extra Medullary Relapse (EMR) is less common, the incidence of EMR in the literature ranges from 0.65% up to 41%. Objective: To study the characteristics, outcomes and risk Factors of EMR post Allo-HSCT for adult AML, and to compare with Isolated Medullary Relapse (IMR). Design: Retrospective Study included AML patients, who underwent AlloHSCT from January 2005 to December 2015. Setting: Single institution study from King Faisal specialist hospital and Research Center, Riyadh, KSA. Patients: A total of 268 patients, 95 experienced disease relapse, 59 had IMR and 36 had EMR with or