Contributions
Abstract: PB1629
Type: Publication Only
Background
Adult patients (pts) diagnosed with acute lymphoblastic leukemia (ALL), are considered to have dismal outcome compare to pediatric/adolescent pts. The last two decades the incorporation of pediatric therapeutic protocols in adults–ALL treatment, resulted in promising response and survival rates, however their use still remains an experimental approach, not representing the standard of care for adult-ALL pts.
Aims
In the present study we retrospectively evaluated the outcome in terms of toxicity, complete remission (CR) achievement and overall (OS) and progression free survival (PFS), in 52 adult-ALL pts adult pts who treated with a pediatric-ALL protocol
Methods
From January 2008 to December 2017, the Children Cancer Group-1961(CCG-1961) protocol which includes Doxorubicin, Vincristin , Asparaginase, Methotrexate and Cytarabine in induction remission (InRe) and consolidation phases, was applied in 34 males and 18 females, with a median age of 21 (16-54) years. Patients with concurrent malignancies or severe co-morbitities were excluded. In 42 the malignant cells were B- and in 10 T-origin. Two pts had CNS involvement, 8 had >50000/mm3 WBCs in the peripheral blood, while 11 found to have poor risk cytogenetic or molecular abnormalities. As per protocol instructions, candidates for allogeneic stem cell transplantation (alloSCT) considered only pts with either minimal residual disease (MRD) post InRe phase or relapsed disease. All patients received antibacterial, antiviral, anti-PCP and antifungal prophylaxis Disease response was assessed at day +28 after treatment initiation. The Kaplan-Meir and log-rank tests were used for the statistical analysis.
Results
Currently, 52 pts completed the InRe and consolidation arm and 11 are in ongoing treatment. Two pts discontinued early the treatment (during the consolidation phase) because of either severe liver toxicity or intolerable mucositis (grade4). The grade 3 observed toxicities, which did not compromise the treatment plan, were febrile neutropenia in 40 (75%), liver dysfunction (elevation of liver enzymes by 3-fold) in 32 (60%), peripheral neuropathy in 4 (7%), mucositis in 7 (14%), thrombosis in 6 (11%) which was mostly venous catheter related, cardiac toxicity in 3 (6%) while 7(14%) required admission in intensive care unit. No pt experienced mortality related to the treatment protocol. In a total 46 pts were evaluated for disease response while in 6 the assessment was not avaiable; 43 (85%) were estimated to be in CR. Three (6%) had refractory disease while 11(25%) relapsed during or after protocol completion; 5/14 succumbed early due to disease refractoriness and 9 were finally able to undergo alloSCT and currently 4/9 (45%) are alive and disease free. The 2 pts who experienced severe toxicity and intolerability during consolidation treatment, underwent early alloSCT and currently are alive and well. The 11 pts with unfavorable cytogenetic/molecular abnormalities, based on protocol instructions, were not allografted in CR1 and continued with the as per protocol scheduled treatment. Five (45%) are currently alive without disease evidence. The 10-years OS and PFS (including the alloSCT treatment) are 60% and 40% respectively
Conclusion
Our study showed that the application of the CCG-1961 pediatric protocol in adult pts is feasible, offering CR rates of 85% and long term survival of 60%. However, its toxicity seems to be considerable. Prospective well organized trials with large series of patients are needed to define the role of intensive pediatric protocol in the treatment of adults-ALL
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, chemotherapy
Abstract: PB1629
Type: Publication Only
Background
Adult patients (pts) diagnosed with acute lymphoblastic leukemia (ALL), are considered to have dismal outcome compare to pediatric/adolescent pts. The last two decades the incorporation of pediatric therapeutic protocols in adults–ALL treatment, resulted in promising response and survival rates, however their use still remains an experimental approach, not representing the standard of care for adult-ALL pts.
Aims
In the present study we retrospectively evaluated the outcome in terms of toxicity, complete remission (CR) achievement and overall (OS) and progression free survival (PFS), in 52 adult-ALL pts adult pts who treated with a pediatric-ALL protocol
Methods
From January 2008 to December 2017, the Children Cancer Group-1961(CCG-1961) protocol which includes Doxorubicin, Vincristin , Asparaginase, Methotrexate and Cytarabine in induction remission (InRe) and consolidation phases, was applied in 34 males and 18 females, with a median age of 21 (16-54) years. Patients with concurrent malignancies or severe co-morbitities were excluded. In 42 the malignant cells were B- and in 10 T-origin. Two pts had CNS involvement, 8 had >50000/mm3 WBCs in the peripheral blood, while 11 found to have poor risk cytogenetic or molecular abnormalities. As per protocol instructions, candidates for allogeneic stem cell transplantation (alloSCT) considered only pts with either minimal residual disease (MRD) post InRe phase or relapsed disease. All patients received antibacterial, antiviral, anti-PCP and antifungal prophylaxis Disease response was assessed at day +28 after treatment initiation. The Kaplan-Meir and log-rank tests were used for the statistical analysis.
Results
Currently, 52 pts completed the InRe and consolidation arm and 11 are in ongoing treatment. Two pts discontinued early the treatment (during the consolidation phase) because of either severe liver toxicity or intolerable mucositis (grade4). The grade 3 observed toxicities, which did not compromise the treatment plan, were febrile neutropenia in 40 (75%), liver dysfunction (elevation of liver enzymes by 3-fold) in 32 (60%), peripheral neuropathy in 4 (7%), mucositis in 7 (14%), thrombosis in 6 (11%) which was mostly venous catheter related, cardiac toxicity in 3 (6%) while 7(14%) required admission in intensive care unit. No pt experienced mortality related to the treatment protocol. In a total 46 pts were evaluated for disease response while in 6 the assessment was not avaiable; 43 (85%) were estimated to be in CR. Three (6%) had refractory disease while 11(25%) relapsed during or after protocol completion; 5/14 succumbed early due to disease refractoriness and 9 were finally able to undergo alloSCT and currently 4/9 (45%) are alive and disease free. The 2 pts who experienced severe toxicity and intolerability during consolidation treatment, underwent early alloSCT and currently are alive and well. The 11 pts with unfavorable cytogenetic/molecular abnormalities, based on protocol instructions, were not allografted in CR1 and continued with the as per protocol scheduled treatment. Five (45%) are currently alive without disease evidence. The 10-years OS and PFS (including the alloSCT treatment) are 60% and 40% respectively
Conclusion
Our study showed that the application of the CCG-1961 pediatric protocol in adult pts is feasible, offering CR rates of 85% and long term survival of 60%. However, its toxicity seems to be considerable. Prospective well organized trials with large series of patients are needed to define the role of intensive pediatric protocol in the treatment of adults-ALL
Session topic: 2. Acute lymphoblastic leukemia - Clinical
Keyword(s): Acute lymphoblastic leukemia, chemotherapy