
Contributions
Type: Publication Only
Background
Anaplastic large cell lymphoma (ALCL) is an aggressive T cell non-Hodgkin lymphoma, characterized by an increased risk of relapse. Its presentation maybe cutaneous or systemic. It is classified on the basis of the expression of anaplastic lymphoma kinase (ALK) protein, which carries the translocation t(2;5)(p23;q35) and results in the specific fusion gene Nucleophosmin (NPM-ALK). In 50% to 60% of patients with NPM-ALK–positive ALCL, NPM-ALK–expressing cells can be detected in peripheral blood and bone marrow samples by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR). ALCL is designated by the uniform expression of CD30, making this surface antigen a target for immunotherapeutic approaches.
Aims
The purpose of the present report was the evaluation of minimal residual disease in children with ALCL and its usage in guiding treatment with targeted therapy, namely the anti-CD30 antibody-drug conjugate, Brentuximab vedotin.
Methods
RT-PCR for NPM-ALK was performed in bone marrow or peripheral blood samples in two pediatric patients with NPM-ALK–positive ALCL, at regular time points.
Results
The first patient is an 11-year-old girl with systemic NPM-ALK–positive (lymphadenopathy, skin, orbit and central nervous system involvement). She achieved remission and completed chemotherapy based on the AEIOP protocol. Three months after treatment completion she presented with disseminated relapse and required ventillatory support. She started targeted treatment with Brentuximab vedotin. She promptly responded to the treatment and she was able to be weaned off ventillatory support within 3 days after the infusion. The patient entered clinical and radiological remission (MRI and PET scan) with Brentuximab vedotin given at dose of 1.8 mg/kg IV every 3 weeks. She received a total of 6 cycles and subsequently underwent mega-therapy with autologous bone marrow transplantation rescue. Six months after transplantation, RT-PCR for NPM-ALK became positive, while the patient remained in clinical remission and the imaging examinations were negative for disease. Brentuximab vedotin was reinstituted and she entered molecular remission with negative minimal residual disease after the 5th cycle. The second patient is a 9-year-old boy with systemic NPM-ALK–positive ALCL, presenting with an abdominal primary mass. He completed chemotherapy and is monitored by radiological examinations and RT-PCR for NPM-ALK at regular time points. Minimal residual disease in this patient remains negative six months after the end of therapy.
Summary
Recent advances in the treatment of adult patients with NPM-ALK–positive ALCL have led to better follow up and expanded options of therapeutic modalities, especially for patients who relapse. Early detection of relapse by assessing minimal residual disease with molecular techniques seems to be superior to classical clinical risk features, identifying a high risk for overt relapse group of patients, which can be amenable by alternative therapeutic approaches. In conclusion, the potential use of minimal residual disease detection and second-line treatment like the novel antibody-drug conjugate, Brentuximab vedotin, warrant further evaluation for pediatric patients with CD30-expressing ALCL.
Keyword(s): Anaplastic large cell lymphoma, Anaplastic lymphoma kinase, Real time PCR, Targeted therapy
Session topic: Publication Only
Type: Publication Only
Background
Anaplastic large cell lymphoma (ALCL) is an aggressive T cell non-Hodgkin lymphoma, characterized by an increased risk of relapse. Its presentation maybe cutaneous or systemic. It is classified on the basis of the expression of anaplastic lymphoma kinase (ALK) protein, which carries the translocation t(2;5)(p23;q35) and results in the specific fusion gene Nucleophosmin (NPM-ALK). In 50% to 60% of patients with NPM-ALK–positive ALCL, NPM-ALK–expressing cells can be detected in peripheral blood and bone marrow samples by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR). ALCL is designated by the uniform expression of CD30, making this surface antigen a target for immunotherapeutic approaches.
Aims
The purpose of the present report was the evaluation of minimal residual disease in children with ALCL and its usage in guiding treatment with targeted therapy, namely the anti-CD30 antibody-drug conjugate, Brentuximab vedotin.
Methods
RT-PCR for NPM-ALK was performed in bone marrow or peripheral blood samples in two pediatric patients with NPM-ALK–positive ALCL, at regular time points.
Results
The first patient is an 11-year-old girl with systemic NPM-ALK–positive (lymphadenopathy, skin, orbit and central nervous system involvement). She achieved remission and completed chemotherapy based on the AEIOP protocol. Three months after treatment completion she presented with disseminated relapse and required ventillatory support. She started targeted treatment with Brentuximab vedotin. She promptly responded to the treatment and she was able to be weaned off ventillatory support within 3 days after the infusion. The patient entered clinical and radiological remission (MRI and PET scan) with Brentuximab vedotin given at dose of 1.8 mg/kg IV every 3 weeks. She received a total of 6 cycles and subsequently underwent mega-therapy with autologous bone marrow transplantation rescue. Six months after transplantation, RT-PCR for NPM-ALK became positive, while the patient remained in clinical remission and the imaging examinations were negative for disease. Brentuximab vedotin was reinstituted and she entered molecular remission with negative minimal residual disease after the 5th cycle. The second patient is a 9-year-old boy with systemic NPM-ALK–positive ALCL, presenting with an abdominal primary mass. He completed chemotherapy and is monitored by radiological examinations and RT-PCR for NPM-ALK at regular time points. Minimal residual disease in this patient remains negative six months after the end of therapy.
Summary
Recent advances in the treatment of adult patients with NPM-ALK–positive ALCL have led to better follow up and expanded options of therapeutic modalities, especially for patients who relapse. Early detection of relapse by assessing minimal residual disease with molecular techniques seems to be superior to classical clinical risk features, identifying a high risk for overt relapse group of patients, which can be amenable by alternative therapeutic approaches. In conclusion, the potential use of minimal residual disease detection and second-line treatment like the novel antibody-drug conjugate, Brentuximab vedotin, warrant further evaluation for pediatric patients with CD30-expressing ALCL.
Keyword(s): Anaplastic large cell lymphoma, Anaplastic lymphoma kinase, Real time PCR, Targeted therapy
Session topic: Publication Only