NCOG-36. LONG-TERM SURVIVAL AND COGNITIVE FUNCTION FOLLOW UP OF PRIMARY CNS LYMPHOMA TREATED WITH R-MVP FOLLOWED BY HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL TRANSPLANT CONSOLIDATION

BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare central nervous system malignancy, and long-term follow up studies are uncommon. First line therapy is based on high-dose methotrexate and different consolidation therapy options. This is a long-term follow up study of PCNSL patients enrolled in a prospective trial using R-MPV chemotherapy regimen followed by high dose chemotherapy and autologous stem cell rescue to determine long-term survival and cognitive effects. METHODS From June 2005 to September 2011, 32 newly diagnosed immunocompentent PCNSL were enrolled. Patients received 5-7 doses of rituximab (500mg/m2), methotrexate (3.5 gm/m2), procarbazine (100mg/m2), and vincristine (1.4mg/m2) (R-MVP). Consolidation therapy consisted of high dose chemotherapy (HDC) with thiotepa (250 mg/m2), busulfan (3.2 mg/kg), and cyclophosphamide (60 mg/kg), followed by autologous stem cell rescue (ASCT) in those with partial or complete response to R-MVP. Long-term follow-up status including disease status, cognitive status (KPS, NANO score), and leukoencephalopathy (modified Fazkas Scale) were collected. RESULTS 26 of 36 underwent HDC and ACST. Of those, 3 died due to treatment related effects; 2 died of disease progression within two years after ASCT. After a median follow-up of 10.5 years, none of the remaining 21 patients progressed. At the time of last follow up, the median KPS was 90, compared to 80 at time of ASCT. The median NANO score and leukoencephalopathy score post ASCT and at follow-up did not change. Of note, 2 of 4 patients with a partial or complete response to R-MVP that elected not to proceed with HDC-ASCT consolidation, experienced progression at a mean of 52 months. CONCLUSION Long-term follow up demonstrates that treatment was tolerated well with stable leukoencephalopathy on MRI and good performance status. Disease recurrence 2 years after HDC with ASCT consolidation was not observed.

Concurrent Extramedullary Hematopoiesis and Pseudometastatic Hypervascular Lesions Masquerading as Metastases in Liver in a Case of Neuroblastoma

Neuroblastoma is a common embryonic tumor presenting in childhood. Improving treatment protocols which include a combination of chemotherapy, surgical resection, hematopoietic stem cell rescue, and radiation therapy have tremendously improved outcomes. Childhood survivors are at risk of developing lesions which may mimic metastases. It is essential to accurately diagnose these due to its prognostic implications.

Pretransplant Determinants of Outcome in Patients with Myeloma Undergoing Autologous Transplantation in Lower Resource Settings

The treatment landscape in multiple myeloma has significantly changed since the introduction of high-dose melphalan with autologous stem cell rescue in the 1980s. Many randomised controlled trials have clearly demonstrated the superiority of autologous stem cell transplantation in improving survival compared to conventional chemotherapy. However, outcomes in myeloma are highly variable with median survival as short as 2 years and as long as 10 years or more. The main adverse factor predicting shorter survival is presence of high-risk cytogenetics. However, there are many other potential factors that can contribute to the treatment outcomes. This review looks at the various pretransplant variables that are associated with post-transplant outcomes in myeloma.

ATRT-08. TARGETING THE TP53-MDM2 ENHANCES RADIATION SENSITIVITY IN ATRT

Atypical Teratoid Rhabdoid Tumor is a highly aggressive pediatric brain tumor. Despite radiation, aggressive chemotherapy and autologous stem cell rescue, the children usually have poor survival. A functional genomic screen identified the TP53-MDM2 axis as a therapeutic vulnerability in ATRT. Gene expression demonstrates that all ATRT sub-groups have high level of MDM2 a negative regulator of p53. We demonstrate that MDM2 inhibition by shRNA or with small-molecule drugs, Nutlin3 and Idasanutlin resulted in decreased ATRT cell growth, inhibition of clonogenic potential and induction of apoptosis in vitro and in vivo. MRI imaging of intracranial tumors shows that Apparent Diffusion Coefficient (ADC), a good marker for successful treatment, significantly increased with Idasanutlin treatment showing tumor necrosis. Moreover, Idasanutlin significantly decreased growth of intracranial orthotopic ATRT brain tumors as evaluated by T2 MRI imaging and prolonged survival compared to control animals. Further idasanutlin potentiated radiation induced DNA damage and increased sensitivity to radiaton of ATRT cells. These findings highlight the TP53-MDM2 axis as a rational therapeutic target in ATRT.

Factors Modifying Outcome After MIBG Therapy in Children With Neuroblastoma—A National Retrospective Study

BackgroundNeuroblastoma is the most common pediatric extracranial tumor with varied prognoses, but the survival of treated refractory or relapsing patients remains poor.ObjectiveThis analysis presents the outcomes of children with neuroblastoma undergoing MIBG therapy in Poland in 2006-2019.Study DesignA retrospective cohort of 55 patients with refractory or relapsed neuroblastoma treated with I-131 MIBG in Poland in 2006-2019 was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of second cancers and CI of hypothyroidism. Survival curves were estimated using the Kaplan-Meier method and compared between the cohorts by the log-rank test. Cox modeling was adopted to estimate hazard ratios for OS and EFS, considering factors with P < 0.2.ResultsFifty-five patients with a median age of 78.4 months (range 18-193) with neuroblastoma underwent one or more (4 patients) courses of MIBG I-131 therapy. Fifteen patients were not administered chemotherapy, 3 children received standard-dose chemotherapy, and 37 patients were administered high-dose chemotherapy (HDCT) (busulfan-melphalan in 24 and treosulfan-based in 12 patients). Forty-six patients underwent stem cell transplantation, with autologous (35 patients), haploidentical (6), allogeneic (4), and syngeneic grafts (1). The median time from first MIBG therapy to SCT was 22 days. Children with relapsing tumors had inferior OS compared to those with primary resistant disease (21.2% vs 58.7%, p=0.0045). Survival was better in patients without MYCN gene amplification. MIBG therapy was never curative, except in patients further treated with HDCT with stem cell rescue irrespective of the donor type. 31 patients were referred for immune therapy after MIBG therapy, and the 5-year OS in this group was superior to the untreated children (55.2% vs 32.7%, p=0.003), but the difference in the 5-year EFS was not significant (25.6% vs 32.9%, p=ns). In 3 patients, a second malignancy was diagnosed. In 19.6% of treated children, hypothyroidism was diagnosed within 5 years after MIBG therapy.ConclusionMIBG therapy can be incorporated into the therapeutic strategy of relapsed or resistant neuroblastoma patients as preconditioning with HDCT rather than stand-alone therapy. Follow-up is required due to the incidence of thyroid failure and risk of second cancers.