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Context: Controversies exist in the prognostic value of KIT mutations and the optimal thresholds and time points for measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with CBFB-MYH11. Objective: This study aimed to evaluate the prognostic value of different types of KIT mutations and CBFB-MYH11 quantification in AML patients with CBFB-MYH11 who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or autologous HSCT (auto-HSCT) and the clinical relevance of each transplant strategy in each risk group. Design: We retrospectively evaluated 88 patients who underwent allo-HSCT (n=60) or auto-HSCT (n=28). Setting: A referral center. Patients: Ninety-six consecutive AML patients with CBFB-MYH11 in remission who underwent HSCT at the Catholic Hematology Hospital between 2009 and 2019. After excluding two patients who underwent second HSCT and four patients without data for KIT mutations or pre-transplant CBFB-MYH11 MRD data, 88 patients were finally included in this study. Interventions: Not applicable. Main Outcome Measures: We retrospectively compared survival outcomes according to different types of KIT mutations and CBFB-MYH11 MRD levels. Results: The D816V KIT mutation was significantly associated with post-transplant relapse, contrasting with other types of mutations in KIT. Pre- and post-transplant (3 months after transplant) CBFB-MYH11 MRD assessments were useful for predicting post-transplant relapse and poor survival. The optimal threshold was determined as a 2-log reduction at both time points. In multivariate analysis, the D816V KIT mutation and CBFB-MYH11 MRD assessments were independently associated with post-transplant relapse and survival. Stratification by D816V KIT and pre-transplant CBFB-MYH11 MRD status further distinguished the risk of relapse and survival. Auto-HSCT was superior to allo-HSCT in MRD-negative patients without D816V KIT, while allo-HSCT trended to be superior to auto-HSCT in patients with MRD positivity or the D816V KIT mutation. Conclusions: This study demonstrated the differentiated prognostic value of the D816V KIT mutation in AML with CBFB-MYH11 and clarified the optimal time points and thresholds for CBFB-MYH11 MRD monitoring in the setting of HSCT.

Background Plasmacytoma at the time of relapse of multiple myeloma is associated with poor response and survival. However, data on the activity of the recently available new drug or drug combinations in RRMM with plasmacytoma in the real-world clinical practice is limited. Pomalidomide and dexamethasone (Pd) with or without cyclophosphamide is an active therapeutic combination in relapsed and refractory multiple myeloma (RRMM) after 2 lines of previous line of therapy Method This study aimed to analyze the clinical outcome of the pomalidomide-based regimen in RRMM with plasmacytoma. Clinical data of 221 patients who were treated with Pd with or without cyclophosphamide from 7 hospitals participating in the Korean multiple myeloma working party were retrospectively analyzed by electronic medical chart review. All the of patients were previously treated with at least 2 lines of therapies including bortezomib and lenalidomide in most of the patients. Plasmacytoma was diagnosed by the computed tomography, magnetic resonance imaging or FDG-PET scan Result Twenty-nine patients among the 221 patients analyzed (13.1%) had plasmacytoma at the time of pomalidomide-based chemotherapy. Patients were previously treated with a median 4 lines of therapy (range, 2-14), including bortezomib, lenalidomide, autologous stem cell transplantation in 97%,100%, and 52% of the patients, respectively. 14 patients were treated with Pd and 15 patients had been treated with Pd and cyclophosphamide (PCd). Median number of sites of plasmacytoma involvement was 2 (range, 1-9), including paraskeletal and soft tissue involvement in 83% and 52% of the patients. Sites of soft tissue involvement were: 5 pleura, 4 lymph nodes, 4 subcutaneous, 3 liver, 3 muscle, 2 pancreas, 1 kidney, 1 pericardium, 1 peritoneum, 1 adrenal gland, and 1 stomach. 50% patients (13 among the 26 response evaluable patients) had responded to Pd with or without Cy: 2 complete response, 2 very good partial response, 9 partial response, 1 stable disease, 2 minimal response, and 10 progressive disease. Patients who were treated with PCd showed a better response compared with Pd therapy (53% versus 29%, P=0.264). After a median follow-up of 9.33 months (range, 0.30-52months), patients with plasmacytoma versus no plasmacytoma showed a progression-free survival of 3.57 (95% CI, 0.35-6.78 months) versus 8.40 months (95% CI, 7.00-9.80 months) (P=0.002) and an overall survival of 3.33 (95% CI, 0.00-7.82 months) versus 19.67 months (95% CI, 13.39-25.95 months) (P=0.001). Conclusion RRMM patients with plasmacytoma was responsive after pomalidomide-based chemotherapies. The addition of cyclophosphamide to Pd seemed to result in a better response compared with Pd only. However, RRMM patients with plasmacytoma had poorer survival compared with patients without plasmacytoma even after Pd with or without cyclophosphamide.

Background A high number of focal lesions (FL) detected using PET/CT at diagnosis were found to be associated with adverse prognosis along with Revised International Staging System (R-ISS). In present study, we combined R-ISS with FL using PET/CT to design a reliable and easily applicable risk stratification system in patients with newly diagnosed MM (NDMM). Methods In training cohort, the data of 380 patients with NDMM who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis from 10 hospitals of the Korean Multiple Myeloma Working Party were retrospectively analyzed. All patients were classified by R-ISS and were treated by frontline therapy with proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD). The K-adaptive partitioning algorithm was adopted to develop the new risk groups with homogeneous survival. Sixty-seven patients in external validation cohort were additionally collected to confirm reproducibility of the new risk groups. Results In the training cohort, 199 patients (52.4%) showed FL > 3 using PET/CT at diagnosis. R-ISS stages I, II, and III were 78 patients (20.5%), 230 (60.5%), and 72 (18.9%), respectively. The combined R-ISS with PET/CT newly allocated NDMM patients into four groups: R-ISS/PET stage I (n=30; R-ISS I with FL≤3), stage II (n=149; R-ISS I with FL>3 and R-ISS II with FL≤3), stage III (n=166; R-ISS II with FL>3 and R-ISS III with FL≤3), and stage IV (n=35; R-ISS III with FL>3). The new R-ISS/PET showed significantly pronounced survival differences according to stages. Two-year overall survival (OS) rates were 96.6%, 89.5%, 75.0%, and 57.9% (p Conclusion The new R-ISS/PET had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely.

Background Renal impairment (RI) is a common complication of multiple myeloma (MM) and is associated with an unfavorable prognosis. Several new markers of kidney damage have been introduced in recent years. The aim of this study was to assess whether neutrophil gelatinase-associated lipocalin (NGAL) can be used as a biomarker of RI in patients with MM. Patients and Methods A total of 199 samples from patients with MM were studied. Plasma NGAL, serum creatinine (sCr), cystatin C (Cys-C), serum free light chain (sFLC), and myeloma protein (M protein) concentrations were measured, and estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. Results Plasma NGAL levels significantly correlated with the degree of RI as defined by the Kidney Disease Improving Global Outcomes chronic kidney disease stage and with sCr and Cys-C concentrations and eGFR. Moreover, the plasma NGAL level was predictive of the myeloma burden and showed a significant correlation with sFLC, dFLC (difference between involved and uninvolved FLC), and M-protein concentrations. Conclusion Plasma NGAL is not only a sensitive biomarker of renal function but may also be a useful marker that reflects tumor burden in patients with MM.

Allogeneic hematopoietic stem cell transplant with reduced-intensity conditioning is an effective therapeutic option for patients with refractory or relapsed aggressive non-Hodgkin lymphoma (NHL).We retrospectively evaluated survival outcomes and the efficacy of our fludarabine/melphalan/total body irradiation (TBI) (FMT) regimen. A total of 89 patients had received the FMT regimen from 2007 to 2017.The majority of patients (n = 81; 91%) belonged to the histologic subtype of aggressive NHL. The estimated 3-year overall survival and disease-free survival for the entire cohort during a median follow-up of 31 months were 47.1% (95% confidence interval, 36%-57%) and 45.4% (95% confidence interval, 35%-56%), respectively. The cumulative incidence rates of relapse and non-relapse mortality at 3 years were 33.1% and 13.8%, respectively. In analyses of risk factors affecting survival outcomes, chemosensitive disease status at transplant (hazard ratio [HR], 2.45; P = .010), delayed relapse after first-line chemotherapy (HR, 2.101; P = .009), no grade III to IV acute graft-versus-host disease (HR, 11.212; P .001), and mild chronic graft-versus-host disease (HR, 0.448; P = .016) were independent significant predictors of favorable overall survival. Also, similar parameters were related to favorable disease-free survival. All non-hematologic toxicities occurred within 50 days after allogeneic hematopoietic stem cell transplant, and most of the adverse events were tolerable and manageable with a 30% incidence.Our FMT regimen shows favorable transplant outcomes with relatively low-risk toxicities, so it may be a promising strategy for patients with relapsed or refractory aggressive NHL.

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapid clinical course. In this study, we evaluated the treatment status and survival outcomes of Korean patients with pPCL. Seventy patients were diagnosed with pPCL between February 1998 and December 2015. The median age of the patients was 63.5 years (range, 34-85). Most of patients (70.0%) had International Staging System III.Conventional karyotyping was assessed in 47 patients and FISH analysis was performed in 43 patients. Abnormal karyotype was detected in 34 patients (72.3%). The most common abnormalities were complex karyotype (65.9%). Hypodiploidy, del (13q14), del (17p13), and t(11;14) were found16 (34%), 14 (29%), 12 (25%), and 11 (23%) patients, respectively. Amongthe 70 patients, 60 patients were treated.Thirty-six patients were initially treated with novel agents and 12 received novel-containing regimens as salvage therapy. Twelve patients received conventional chemotherapies only. Twenty-two patients underwent high dose chemotherapy and autologous stem cell transplantation (HDT/ASCT), and one received the allogeneic stem cell transplantation. After a median follow-up of 16.5 months, overall survival (OS) was 16.1 months (95% CI, 11.7-20.8). Twenty patients (33.3%) died within less than one year following the diagnosis, and the early mortality rate was lower in patients who were initially treated with novel agents (22.2% vs. 50.0%, p = 0.049). The median OS of three treatment groups comprising conventional chemotherapy only, novel agents only, and novel agents + HDT/ASCT were 2.9, 12.3, and 31.1 months, respectively (P=0.001). Patients who achieved complete response (CR)after initial therapy had significantly improved OS than did others (36.4 vs. 14.1 months, P 5.5 mg/dl (HR 3.218, 95% CI 1.011-10.238, P = 0.048)were significantly associated with survival outcomes. In young patients (age Disclosures No relevant conflicts of interest to declare.

Background Although the combination of lenalidomide and low-dose dexamethasone (Len-dex) is known to preserve the efficacy with reduced toxicity than lenalidomide plus high-dose dexamethasone (Len-Dex) in patients with refractory/relapsed multiple myeloma (RRMM), infection is still a leading toxicity. Moreover, the patterns and risks for infection in patients with RRMM during Len-dex treatment remain unclear and there is a need to identify contributing factors associated with increased risk for infection. Considering the disease-related and treatment-related immune deficits in patients with RRMM, we explored the predictive implications of the revelation of the immune cell populations prior to Len-dex initiation for the occurrence of infection. In addition, the various clinical and laboratory parameters were analyzed. Methods Clinical and microbiology records of 90 RRMM patients during Len-dex treatment were reviewed and risk factors for infection were analyzed using the logistic regression. In addition, to develop the new immune cell biomarker, we prospectively examined immune cell populations (CD3, CD4CD161, CD8CD161, Lin-HLA-DR-CD11b+CD33+, CD14+HLA-DR-, NK and NKT cells) of the peripheral blood taken on baseline of Len-dex therapy. Results Forty-eight men and 42 women were enrolled in this study. The median age was 61 years (range, 29-84 years). During a median 11 cycles of Len-dex treatment, 52 (57.8%) patients experienced at least 1 infection episode. Of a total of 92 episodes of infection, 58 (63%) episodes were clinically defined, 29 (31.5%) episodes were microbiologically defined, and 5 (5.4%) episodes were fever of unknown focus. Severe episodes were frequently observed during early 3 cycles. In the univariate analyses, lower Hb ( + CD161 + cells in peripheral blood prior to Len-dex were associated with the occurrence of infection, especially during early 3 cycles of Len-dex therapy. Conclusions We demonstrated several clinical predictive factors for the occurrence of infection in patients with RRMM receiving Len-dex treatment. And we found that the frequency and absolute count of CD4 + CD161 + cells may provide additional information for predicting the occurrence of infection in early period of Len/dex therapy. Disclosures No relevant conflicts of interest to declare.

e198 the occurrence of VTE), significant conversion of d-dimer from 2.2 0.4 mg/L to 11.8 1.6 mg/L (P

Background Acute myeloid leukemia (AML) with t(8;21)(q22;q22) is classified into a favorable-risk group. Extramedullary (EM) involvement has frequently been reported in this subgroup as resulting in a poor prognosis. However, characteristics or standard treatments of t(8;21) AML with EM involvement (EM-positive t(8;21)) have not yet been elucidated. Patients and Methods We retrospectively analyzed 154 adult AML patients with t(8;21). Among them, 17 were EM positive and 137 were EM negative at the time of diagnosis. EM involvement was evaluated only when a patient showed suspicious signs or symptoms. All EM-positive patients were treated according to a strategy based on allogeneic hematopoietic cell transplantation (allo-HCT). Results Central nervous system was the most frequently involved site (70.6%). EM-positive t(8;21) was associated with age ≤ 45 years, leukocytosis (≥ 30 × 10 9 /L), and c-kit mutation compared to EM-negative t(8;21) in multivariate analysis. After intensive chemotherapy with or without local therapy, high-risk t(8;21) AML including EM-positive t(8;21) underwent allo-HCT for postremission therapy. Three-year OS (52.3% vs. 60.0%, P = .658) and event-free survival (51.5% vs. 58.0%, P = .496) were not different between the 2 groups. The subgroup of patients who underwent allo-HCT also showed similar outcomes. Conclusion EM-positive t(8;21) was associated with young age, leukocytosis, and c-kit mutation, and central nervous system was frequently involved. Allo-HCT resulted in good outcomes in EM-positive t(8;21).

FH Campus Vienna, University of Applied Sciences, Vienna, Austria; Department of Laboratory Medicine, Wilhelminenhospital, Vienna; Wilhelminen Cancer Research Institute, c/o Department of Medicine I, Center of Oncology, Hematology with Outpatient Department and Palliative Care, Wilheminenhospital, Vienna, Austria Background: Up to 10% of newly diagnosed multiple myeloma (MM) patients present with oligosecretory disease. In these instances serum free light chain (FLC) measurements are recommended for monitoring M-Ig changes; provided FLC ratio is abnormal and involved FLC (iFLC) >100 mg/L at presentation. Novel immunoassays have become available that measure immunoglobulin heavy/light chain (HLC) subsets and may offer a sensitive method of monitoring oligosecretory patients. Patients and Methods: FLC and and HLC Ig’ and Ig’ were quantified turbidimetrically in sequential sera from 16 oligosecretory MM patients (6 IgG and 10 IgA) assessed at Wilhelminenspital, Vienna, Austria. Median age was 72 (53-90) years and median follow-up 992 (2533743) days. 9/16 patients were ISS stage 1, 3/16 were ISS stage 2 and 4/16 were ISS stage 3. HLC measurements were compared to serum protein electrophoresis (SPE) and nephelometric total Ig’ concentrations. Results: In 6/16 patients the M-Ig bands were nonquantifiable by SPEP and in the remaining 10/16 patients the M-Ig concentrations were 100 mg/L; and could be monitored by serum FLC measurements. For the remaining 8/16 patients none of the standard techniques provided information for monitoring M-Ig changes. All 8/8 patients had an abnormal HLC ratio and 5/8 had elevated involved HLC (iHLC) concentrations (IgA n1⁄43, HLC ratio: 6.7 (2.9-85.5), iHLC: 7.0 (3.1-8.6) g/L; IgA n1⁄42, HLC ratio: 0.08 and 0.05; iHLC: 5.9 and 5.0 g/L). In these 5 patients there was overall concordance between changes in HLC ratio /dHLC (involved-uninvolved HLC) and clinical assessment. Importantly in 2/3 patients an increasingly abnormal HLC ratio and dHLC preceded relapse; including 1 IgA patient where immunofixation remained negative and total IgA concentrations within the normal range for 12 months before progression. Conclusion: HLC immunoassays may offer a sensitive method of quantifying M-Ig concentrations in oligosecretory MM patients. Further studies on larger cohorts and comparison with clinical assessment are necessary to validate the assays for monitoring these patients.

Background: Lenalidomide combined with low-dose dexamethasone (Len-dex) is an effective treatment for the patients with refractory/relapsed multiple myeloma (RRMM). The anti-myeloma effect of lenalidomide is associated with activation of the immune system, but the exact immunomodulatory mechanisms in vivo and clinical impact of Len/dex in RRMM patients remains unclear. In this study, we analyzed immune cell populations in patients receiving Len-dex for the treatment of RRMM. Methods: Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len/dex therapy. CD3+, CD4+, CD8+, CD161+ T cells, natural killer (NK) cell (CD16+/CD56+), NKT-like cell (CD3+/CD56+) and myeloid-derived suppressor cell (MDSC) including granulocytic (G-MDSC) and monocytic (M-MDSC) were analyzed by flow cytometry. In addition, response was assessed in 81 patients receiving more than 4 cycles of Len-dex and the comparison of cell populations according to an achievement of ≥very good partial response (VGPR) was performed. Results: Forty-eight men and 42 women were enrolled in this study. The median age was 61 years (range, 29-84 years). At baseline, peripheral blood CD3+ cell frequency was 51.65 ± 1.79% which was significantly decreased to 41.67 ± 2.44% (P=0.001) and 39.72 ± 2.90% (P Conclusion: Our data demonstrate that Len-dex therapy in patients with RRMM is associated with decreased frequency of T cells with a trend of increased NK cell frequency. Change in CD8+ cell and M-MDSC frequency can correlate with the quality of response to Len-dex. Baseline NKT-like cell frequency and change in CD3+ and CD8+ cells early after treatment may predict continuation of anti-myeloma effect of Len-dex therapy. Disclosures No relevant conflicts of interest to declare.