Real-world Experience of Improvement in the Survival of Lymphoma and Myeloma Patients with Autologous Stem Cell Transplantation over a 25-year Period

Background/Aims: The first autologous peripheral blood stem cell transplantation (ASCT) in Korea was performed for a small-cell lung cancer patient at Asan Medical Center (AMC) in 1993. Recently, lymphoma and myeloma have been the main indications; there has been progress in the treatments for these lymphoid malignancies. We explored the real-world experience of ASCT for lymphoma and myeloma at AMC over a 25-year period.Methods: We used the AMC ASCT registry, which has collected ASCT data prospectively since January 1993. Data for Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma patients were analyzed. Patients transplanted up to December 2018 were included to assess adequate survival data. The ASCT time period was divided arbitrarily into 1994-1999, 2000-2009, and 2010-2018. In cases of multiple myeloma, we analyzed the 1st ASCT data only.Results: Survival of these lymphoid malignancy patients after ASCT has progressively improved. The increase in survival may be related to advances in various medical skills supporting ASCT. However, overall survival has improved much more than progression-free survival. This suggests that better salvage therapies after ASCT failure have mainly affected the improvement in overall survival. The hematopoietic cell transplantation-specific comorbidity index could not be used as a survival indicator in this analysis.Conclusions: This real-world experience study showed that the survival of lymphoid malignancy patients treated with ASCT has improved over the past 25 years.

Hematologic Complications with Age in Shwachman-Diamond Syndrome

Shwachman-Diamond Syndrome (SDS) is an inherited bone marrow failure syndrome with leukemia predisposition. An understanding of the hematologic complications of SDS with age could guide clinical management, but data are limited for this rare disease. We conducted a cohort study of 153 subjects from 143 families with confirmed biallelic SBDS mutations enrolled on the North American Shwachman Diamond Registry or Bone Marrow Failure Registry. The SBDS c.258+2T>C variant was present in all but one patient. To evaluate association of blood counts with age, a total of 2146 blood counts were analyzed for 119 subjects. Absolute neutrophil counts were positively associated with age (P<0.0001). Hemoglobin was also positively associated with age up to 18 years (P<0.0001) but thereafter the association was negative (P=0.0079). Platelet counts and marrow cellularity were negatively associated with age (P<0.0001). Marrow cellularity did not correlate with blood counts. Severe marrow failure necessitating transplant developed in 8 subjects at a median age of 1.7 years (range 0.4-39.5), with 7 of 8 requiring transplant prior to age 8 years. Twenty-six subjects (17%) developed a myeloid malignancy (16 MDS and 10 AML) at a median age of 12.3 years (range 0.5-45.0) for MDS, and 28.4 years (range 14.4-47.3) for AML. A lymphoid malignancy developed in one patient at the age of 16.9 years. Hematologic complications were the major cause of mortality (17/20 deaths, 85%). These data inform surveillance of hematologic complications in SDS.

586. Immunogenicity of COVID-19 mRNA Vaccines in Patients with Lymphoid Malignancies

Background Patients with lymphoid malignancies are at high risk of severe COVID-19 disease and were not included in the phase 3 mRNA vaccine trials. Many patients with lymphoid malignancies receive immunosuppressive therapies, including B-cell depleting agents, that may negatively impact humoral response to vaccination. Methods We recruited patients with lymphoid malignancies and healthy participants who planned to receive two doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). Blood was drawn at baseline, prior to second dose of vaccine, and 28 days after last vaccination. Disease characteristics and therapies were extracted from patients’ electronic medical record. An ultrasensitive, single molecule array (Simoa) assay detected anti-Spike (S), anti-S1, anti-receptor binding domain (RBD), and anti-Nucleocapsid (N) IgG from plasma at each timepoint. Results 23 healthy participants and 37 patients with lymphoid malignancies were enrolled (Table 1). Low titers of anti-N (Fig 1A) demonstrate no prior exposure or acquisition of COVID-19 before vaccination or during the study. 37.8% of the lymphoid malignancy cohort responded to the vaccine, using an internally validated AEB cutoff of 1.07. A significantly higher magnitude of anti-S (p< 0.0001), anti-S1 (p< 0.0001) and anti-RBD (p< 0.0001) are present in the healthy as compared to lymphoid malignancy cohort at the second dose and day 28 post-series (Fig 1B, Fig 1C and Fig 1D). Anti-S IgG titers were compared between the healthy cohort, treatment naïve, and treatment experienced groups (Fig 2). The treatment naïve cohort had high titers by series completion which were not significantly different from the healthy cohort (p=0.2259), although the treatment experienced group had significantly decreased titers (p< 0.0001). Of the 20 patients who had received CD20 therapy, there was no clear correlation of anti-S IgG response with time from CD20 therapy, although most patients who received CD20 therapies within 12 months from the vaccine had no response (Figure 3). Table 1. Demographics Figure 1. Anti-N, Anti-S, Anti-S1, Anti-RBD and Anti-N Ig G for healthy v. lymphoid malignancy cohort The dotted line at 1.07 marks in an internally validated threshold to mark anti-S IgG response. The black bars denote median with 95% CI. Figure 2: Anti-S IgG for healthy v. treatment naïve v. treatment experienced The dotted line at 1.07 marks in an internally validated threshold to mark antibody response. The black bars denote median with 95% CI. Conclusion The vaccine-induced immune response was poor among treatment-experienced patients with lymphoid malignancies, especially among those who received CD20 therapies within 12 months. Figure 3. Months from CD20 therapy v. anti-S IgG titers The dotted line at 1.07 marks in an internally validated threshold to mark antibody response. Disclosures Jennifer Crombie, MD, AbbVie (Grant/Research Support)Bauer (Grant/Research Support)Karyopharm (Consultant)MorphoSys (Consultant) Philippe Armand, MD PhD, ADCT, Celgene, Morphosys, Daiichi, Miltenyi, Tessa, C4, Genmab, Enterome, Regeneron, Genentech, Epizyme, Astra Zeneca (Consultant, Sorry to put them all in, hope you can deconvolute for me)Affimed, Adaptive, BMS, Merck, Kite, IGM, Genentech (Research Grant or Support, Institutional research funding) David Walt, PhD, Quanterix Corporation (Board Member, Shareholder) Nicolas C. Issa, MD, AiCuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)GSK (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)

Predictive and Prognostic Molecular Factors in Diffuse Large B-Cell Lymphomas

Diffuse large B-cell lymphoma (DLBCL) is the commonest form of lymphoid malignancy, with a prevalence of about 40% worldwide. Its classification encompasses a common form, also termed as “not otherwise specified” (NOS), and a series of variants, which are rare and at least in part related to viral agents. Over the last two decades, DLBCL-NOS, which accounts for more than 80% of the neoplasms included in the DLBCL chapter, has been the object of an increasing number of molecular studies which have led to the identification of prognostic/predictive factors that are increasingly entering daily practice. In this review, the main achievements obtained by gene expression profiling (with respect to both neoplastic cells and the microenvironment) and next-generation sequencing will be discussed and compared. Only the amalgamation of molecular attributes will lead to the achievement of the long-term goal of using tailored therapies and possibly chemotherapy-free protocols capable of curing most (if not all) patients with minimal or no toxic effects.

Secondary EBV-positive Diffuse Large B-cell Lymphoma of Skeletal Muscle from EBV-positive Primary Diffuse Large B-cell Lymphoma of Thyroid Gland: Case Report and Literature Review

Diffuse Large B-Cell Lymphoma (DLBCL) is the most common lymphoid malignancy in adults, which often takes a nonlymph nodes organ as the primary focus. Primary lymphoid malignancy of thyroid gland is not common in clinic, EBV-positive primary diffuse large B-cell lymphoma of thyroid gland is rare in clinic, and its pathogenesis, treatment and prognosis are rarely studied. We reported an 85-year-old female patient with EBV-positive primary diffuse large B-cell lymphoma of thyroid gland, and the disease eventually relapsed in skeletal muscle of the patient. The pathological type after relapse was consistent with that of the primary focus. As far as we know secondary EBV-positive DLBCL of skeletal muscle from EBV-positive primary DLBCL of thyroid gland. For elderly patients with multiple adverse prognostic factors, individualized treatment on the premise of ensuring their quality of life may be more important.