ARSENIC TRIOXIDE AS THE FIRST LINE THERAPY FOR PATIENTS WITH SECONDARY MITOXANTRONE-RELATED ACUTE PROMYELOCYTIC LEUKEMIA ON THE BACKGROUND OF MULTIPLE SCLEROSIS
(Abstract release date: 05/19/16)
EHA Library. Lobanova T. 06/09/16; 134575; PB1675
Ms. Tatiana Lobanova
Contributions
Contributions
Abstract
Abstract: PB1675
Type: Publication Only
Background
Mitoxantrone (MT) is a topoisomerase II inhibitor which impairs DNA repair mechanisms. It is well known to induce acute leukemia with absence of myelodysplastic phase. MT therapy is often associated with translocation t(15;17), which defines the development of acute promyelocytic leukemia (APL). MT remains an effective drug for treatment of remitting progressive phase of multiple sclerosis (MS). The APL risk in patients with MS depends on MT dose (≤60mg/m2, ≥60mg/m2). Long MS anamnesis, severity of somatic status and evolvement of therapy-related acute leukemia (TRAL) in such patients requires new approaches to treatment.
Aims
To describe the optimal treatment protocols for MS patients with APL, taking into account the patients somatic status.
Methods
From January 2014 to February 2016 in the Department of Hematological Oncology and BMT 15 pts with APL were treated, and 2 of them (39 and 58 y.o.) were with long anamnesis (over 15 years) of MS (remitting progressive phase, cerebral-spinal form). First patient (pt) due to fast progression of MS got MT therapy several times a year, in total≥60mg/m2, second pt received MT with 60mg in total. Both pts developed APL after 2 years of MT injections. Severity of somatic status was determined by hemorrhagic syndrome (skin and mucosa), coagulation disturbances, granulocytopenia and lower paraparesis with pelvic organs dysfunction due to MS. Pts had intermediate risk APL, cytogenetic analysis showed translocation t(15;17), molecular – bcr1 transcript in both cases.
Results
For the first patient we started all trans-retinoic acid (ATRA) therapy with arsenic trioxide (ATO). Good tolerance to treatment was stated. After 1 month of treatment APL molecular remission was established. The neutropenia period lasted 6 days; catheter-associated sepsis, vaginal and urinary infections, QTc lengthening to 0,48ms were diagnosed. The course of treatment was completed according to ATRA and ATO protocol (E. Estey, 2006). APL remission retains for 16 months. Neurologic symptoms of MS stay stable since the start of APL therapy.The second pt was started with chemotherapy protocol (AIDA), on day 14 he developed septic shock, severe pneumocystis pneumonia with acute respiratory failure. In 2 days he was transferred to the intensive care unit for prolonged invasive mechanical ventilation. Due to long lasting cytopenia (30 days), severe infectious complications, the polyneuropathy deteriorated and tetraplegia developed after status stabilization. ATO therapy with further combination ATRA+ATO was started. Morphological complete remission (CR) and cytogenetic CR were achieved after chemotherapy, molecular CR – after 28 days of ATO. 5 courses of ATO and ATRA+ATO treatment completed. No severe complications were noted and the duration of CR is 8 months. Upper limbs function has recovered, lower limbs – only partially.
Conclusion
Our experience shows high toxicity of chemotherapy protocol in APL patients with MS. Such protocols cause severe infectious complications due to long period of immunosuppression and may worsen the neurologic status. ATO and ATRA combination as the first line therapy of therapy-related APL in such pts allows to achieve molecular remission with lower toxic effects and without deterioration of MS course.
Session topic: E-poster
Keyword(s): Acute promyelocytic leukemia, Infection, Pancytopenia, Toxicity
Type: Publication Only
Background
Mitoxantrone (MT) is a topoisomerase II inhibitor which impairs DNA repair mechanisms. It is well known to induce acute leukemia with absence of myelodysplastic phase. MT therapy is often associated with translocation t(15;17), which defines the development of acute promyelocytic leukemia (APL). MT remains an effective drug for treatment of remitting progressive phase of multiple sclerosis (MS). The APL risk in patients with MS depends on MT dose (≤60mg/m2, ≥60mg/m2). Long MS anamnesis, severity of somatic status and evolvement of therapy-related acute leukemia (TRAL) in such patients requires new approaches to treatment.
Aims
To describe the optimal treatment protocols for MS patients with APL, taking into account the patients somatic status.
Methods
From January 2014 to February 2016 in the Department of Hematological Oncology and BMT 15 pts with APL were treated, and 2 of them (39 and 58 y.o.) were with long anamnesis (over 15 years) of MS (remitting progressive phase, cerebral-spinal form). First patient (pt) due to fast progression of MS got MT therapy several times a year, in total≥60mg/m2, second pt received MT with 60mg in total. Both pts developed APL after 2 years of MT injections. Severity of somatic status was determined by hemorrhagic syndrome (skin and mucosa), coagulation disturbances, granulocytopenia and lower paraparesis with pelvic organs dysfunction due to MS. Pts had intermediate risk APL, cytogenetic analysis showed translocation t(15;17), molecular – bcr1 transcript in both cases.
Results
For the first patient we started all trans-retinoic acid (ATRA) therapy with arsenic trioxide (ATO). Good tolerance to treatment was stated. After 1 month of treatment APL molecular remission was established. The neutropenia period lasted 6 days; catheter-associated sepsis, vaginal and urinary infections, QTc lengthening to 0,48ms were diagnosed. The course of treatment was completed according to ATRA and ATO protocol (E. Estey, 2006). APL remission retains for 16 months. Neurologic symptoms of MS stay stable since the start of APL therapy.The second pt was started with chemotherapy protocol (AIDA), on day 14 he developed septic shock, severe pneumocystis pneumonia with acute respiratory failure. In 2 days he was transferred to the intensive care unit for prolonged invasive mechanical ventilation. Due to long lasting cytopenia (30 days), severe infectious complications, the polyneuropathy deteriorated and tetraplegia developed after status stabilization. ATO therapy with further combination ATRA+ATO was started. Morphological complete remission (CR) and cytogenetic CR were achieved after chemotherapy, molecular CR – after 28 days of ATO. 5 courses of ATO and ATRA+ATO treatment completed. No severe complications were noted and the duration of CR is 8 months. Upper limbs function has recovered, lower limbs – only partially.
Conclusion
Our experience shows high toxicity of chemotherapy protocol in APL patients with MS. Such protocols cause severe infectious complications due to long period of immunosuppression and may worsen the neurologic status. ATO and ATRA combination as the first line therapy of therapy-related APL in such pts allows to achieve molecular remission with lower toxic effects and without deterioration of MS course.
Session topic: E-poster
Keyword(s): Acute promyelocytic leukemia, Infection, Pancytopenia, Toxicity
Abstract: PB1675
Type: Publication Only
Background
Mitoxantrone (MT) is a topoisomerase II inhibitor which impairs DNA repair mechanisms. It is well known to induce acute leukemia with absence of myelodysplastic phase. MT therapy is often associated with translocation t(15;17), which defines the development of acute promyelocytic leukemia (APL). MT remains an effective drug for treatment of remitting progressive phase of multiple sclerosis (MS). The APL risk in patients with MS depends on MT dose (≤60mg/m2, ≥60mg/m2). Long MS anamnesis, severity of somatic status and evolvement of therapy-related acute leukemia (TRAL) in such patients requires new approaches to treatment.
Aims
To describe the optimal treatment protocols for MS patients with APL, taking into account the patients somatic status.
Methods
From January 2014 to February 2016 in the Department of Hematological Oncology and BMT 15 pts with APL were treated, and 2 of them (39 and 58 y.o.) were with long anamnesis (over 15 years) of MS (remitting progressive phase, cerebral-spinal form). First patient (pt) due to fast progression of MS got MT therapy several times a year, in total≥60mg/m2, second pt received MT with 60mg in total. Both pts developed APL after 2 years of MT injections. Severity of somatic status was determined by hemorrhagic syndrome (skin and mucosa), coagulation disturbances, granulocytopenia and lower paraparesis with pelvic organs dysfunction due to MS. Pts had intermediate risk APL, cytogenetic analysis showed translocation t(15;17), molecular – bcr1 transcript in both cases.
Results
For the first patient we started all trans-retinoic acid (ATRA) therapy with arsenic trioxide (ATO). Good tolerance to treatment was stated. After 1 month of treatment APL molecular remission was established. The neutropenia period lasted 6 days; catheter-associated sepsis, vaginal and urinary infections, QTc lengthening to 0,48ms were diagnosed. The course of treatment was completed according to ATRA and ATO protocol (E. Estey, 2006). APL remission retains for 16 months. Neurologic symptoms of MS stay stable since the start of APL therapy.The second pt was started with chemotherapy protocol (AIDA), on day 14 he developed septic shock, severe pneumocystis pneumonia with acute respiratory failure. In 2 days he was transferred to the intensive care unit for prolonged invasive mechanical ventilation. Due to long lasting cytopenia (30 days), severe infectious complications, the polyneuropathy deteriorated and tetraplegia developed after status stabilization. ATO therapy with further combination ATRA+ATO was started. Morphological complete remission (CR) and cytogenetic CR were achieved after chemotherapy, molecular CR – after 28 days of ATO. 5 courses of ATO and ATRA+ATO treatment completed. No severe complications were noted and the duration of CR is 8 months. Upper limbs function has recovered, lower limbs – only partially.
Conclusion
Our experience shows high toxicity of chemotherapy protocol in APL patients with MS. Such protocols cause severe infectious complications due to long period of immunosuppression and may worsen the neurologic status. ATO and ATRA combination as the first line therapy of therapy-related APL in such pts allows to achieve molecular remission with lower toxic effects and without deterioration of MS course.
Session topic: E-poster
Keyword(s): Acute promyelocytic leukemia, Infection, Pancytopenia, Toxicity
Type: Publication Only
Background
Mitoxantrone (MT) is a topoisomerase II inhibitor which impairs DNA repair mechanisms. It is well known to induce acute leukemia with absence of myelodysplastic phase. MT therapy is often associated with translocation t(15;17), which defines the development of acute promyelocytic leukemia (APL). MT remains an effective drug for treatment of remitting progressive phase of multiple sclerosis (MS). The APL risk in patients with MS depends on MT dose (≤60mg/m2, ≥60mg/m2). Long MS anamnesis, severity of somatic status and evolvement of therapy-related acute leukemia (TRAL) in such patients requires new approaches to treatment.
Aims
To describe the optimal treatment protocols for MS patients with APL, taking into account the patients somatic status.
Methods
From January 2014 to February 2016 in the Department of Hematological Oncology and BMT 15 pts with APL were treated, and 2 of them (39 and 58 y.o.) were with long anamnesis (over 15 years) of MS (remitting progressive phase, cerebral-spinal form). First patient (pt) due to fast progression of MS got MT therapy several times a year, in total≥60mg/m2, second pt received MT with 60mg in total. Both pts developed APL after 2 years of MT injections. Severity of somatic status was determined by hemorrhagic syndrome (skin and mucosa), coagulation disturbances, granulocytopenia and lower paraparesis with pelvic organs dysfunction due to MS. Pts had intermediate risk APL, cytogenetic analysis showed translocation t(15;17), molecular – bcr1 transcript in both cases.
Results
For the first patient we started all trans-retinoic acid (ATRA) therapy with arsenic trioxide (ATO). Good tolerance to treatment was stated. After 1 month of treatment APL molecular remission was established. The neutropenia period lasted 6 days; catheter-associated sepsis, vaginal and urinary infections, QTc lengthening to 0,48ms were diagnosed. The course of treatment was completed according to ATRA and ATO protocol (E. Estey, 2006). APL remission retains for 16 months. Neurologic symptoms of MS stay stable since the start of APL therapy.The second pt was started with chemotherapy protocol (AIDA), on day 14 he developed septic shock, severe pneumocystis pneumonia with acute respiratory failure. In 2 days he was transferred to the intensive care unit for prolonged invasive mechanical ventilation. Due to long lasting cytopenia (30 days), severe infectious complications, the polyneuropathy deteriorated and tetraplegia developed after status stabilization. ATO therapy with further combination ATRA+ATO was started. Morphological complete remission (CR) and cytogenetic CR were achieved after chemotherapy, molecular CR – after 28 days of ATO. 5 courses of ATO and ATRA+ATO treatment completed. No severe complications were noted and the duration of CR is 8 months. Upper limbs function has recovered, lower limbs – only partially.
Conclusion
Our experience shows high toxicity of chemotherapy protocol in APL patients with MS. Such protocols cause severe infectious complications due to long period of immunosuppression and may worsen the neurologic status. ATO and ATRA combination as the first line therapy of therapy-related APL in such pts allows to achieve molecular remission with lower toxic effects and without deterioration of MS course.
Session topic: E-poster
Keyword(s): Acute promyelocytic leukemia, Infection, Pancytopenia, Toxicity
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