Early dose reduction of dasatinib does not compromise clinical outcomes in patients with chronic myeloid leukemia: A comparative analysis of two prospective trials.

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily. In the PCR-DEPTH study, CP-CML patients who started dasatinib 100 mg daily were enrolled and followed up, while in the DAS-CHANGE study, when patients achieved early molecular response with any grade of AEs were enrolled and treated with dasatinib 80 mg once daily. A total of 102 patients (PCR-DEPTH) and 90 patients (DAS-CHANGE) were compared. Although the median value of the relative dose intensity (RDI) of dasatinib was significantly higher in PCR-DEPTH than in DAS-CHANGE (99.6 % vs. 80.1 %, p <0.001), the MMR rate at 12months showed a trend toward superiority in DAS-CHANGE compared to PCR-DEPTH (77.1 % vs 65.2 %, p = 0.084). The frequencies of MR4.0 at 24 and 36 months were higher in DAS-CHANGE than in PCR-DEPTH (44.4 % vs 28.8 %, p = 0.052 and 63.6 % vs 40.3 %, p= 0.013, respectively). RDIs were not different according to the MMR, MR4.0 or MR4.5 in analyses using a pooled population. Our results suggest that early dose reduction of dasatinib does not compromise efficacy in patients achieving EMR at 3 months and could be an interventional strategy for improving long term outcomes.

Initial Low-Dose Hydroxyurea and Anagrelide Combination in Essential Thrombocythemia: Comparable Response with Lower Toxicity.

Background and Objectives: Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction either with hydroxyurea (HU) or anagrelide (AG) is widely used, but drug intolerance or resistance are major concerns. Low-dose combination of HU and AG as an alternative strategy has been explored in various studies. It showed comparable response with acceptable toxicity in second-line settings for patients who experienced side effects from prior monotherapy. In this study, we evaluated the efficacy and safety of upfront combination for ET patients. Materials and Methods: From January 2018 to June 2022, a total of 241 ET patients with intermediate to high risk were enrolled. We identified 21 patients with initial drug combinations and compared treatment outcomes and adverse events (AEs) between combination and monotherapy groups. Results: The median age was 62 years old (range, 26-87) and median platelet count was 912 × 109/L (range, 520-1720). Overall treatment response did not exhibit significant differences between the groups, although there was a trend towards a lower response rate in patients treated with AG alone at 3 months post-treatment (AG + HU, 85.7% vs. AG alone, 75.4%, p = 0.068). AEs of any grade occurred in 52.3% of the combination group, 44.3% of the HU monotherapy group, and 43.4% of the AG single group, respectively. Of note was that the HU plus AG combination group suffered a lower incidence of grade 3-4 AEs compared to the other two groups, with statistical significance (p = 0.008 for HU monotherapy vs. combination therapy and p < 0.01 for AG monotherapy vs. combination therapy). Conclusions: Our findings demonstrated that the upfront low-dose combination approach showed feasible clinical outcomes with significantly lower severe AEs compared to conventional monotherapy. These results may offer valuable insights to clinicians for future prospective investigations.

Nation-Wide Retrospective Analysis of Allogeneic Stem Cell Transplantation in Patients with Multiple Myeloma: A Study from Korean Multiple Myeloma Working Party (KMM1913).

Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response (sCR) plus CR rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3 and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0, 88.9, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion: AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse.

Clinical significance of bone marrow involvement by immunoglobulin gene rearrangement in de novo diffuse large B-cell lymphoma: a multicenter retrospective study.

Background: Bone marrow (BM) involvement is an indicator of a poor prognosis in diffuse large B-cell lymphoma (DLBCL); however, few studies have evaluated the role of immunoglobulin gene rearrangement (IgR) in detecting BM involvement. Methods: We evaluated the clinical characteristics and treatment outcomes of patients with DLBCL based on histological BM involvement or positive BM IgR using polymerase chain reaction or next-generation sequencing. We also investigated the role of consolidative upfront autologous hematopoietic stem cell transplantation (ASCT) in patients with DLBCL and BM involvement. Results: Among 624 patients, 123 (19.7%) with histological BM involvement and 88 (17.5%) with positive IgR in histologically negative BM had more advanced disease characteristics. Overall (OS) and progression-free (PFS) survival was better for patients with negative BM histology and negative IgR than that in patients with histological BM involvement (P = 0.050 and P < 0.001, respectively) and positive IgR with negative BM histology (P = 0.001 and P = 0.005, respectively). Survival rates did not differ among 82 (13.1%) patients who were treated with upfront ASCT and had histological BM involvement or positive IgR with negative BM histology. The survival outcomes were worse for patients who were not treated with upfront ASCT and for those with histological BM involvement or positive IgR, than for those with negative BM histology and negative IgR. Conclusion: Patients diagnosed with DLBCL and BM involvement based on histology or IgR had aggressive clinical features and poor survival. Upfront ASCT mitigated poor prognosis due to BM involvement.

Open-labeled, multicenter phase II study of prophylactic administration of pegylated granulocyte colony-stimulating factor in relapsed or refractory multiple myeloma who received pomalidomide-based regimens (KMM170).

Introduction: Pegylated granulocyte colony-stimulating factor (G-CSF) has been widely used for preventing febrile neutropenia in various types of cancer treatment. In the present study, we prospectively evaluated the safety and efficacy of pegfilgrastim as a primary prophylaxis of febrile neutropenia and infection among patients with relapsed refractory multiple myeloma (RRMM) treated with pomalidomide-based regimens. Methods: Thirty-three patients with RRMM who received pomalidomide and dexamethasone (Pd) with or without cyclophosphamide (PCd) were enrolled in this study. Twenty-eight patients were treated with PCd and 5 patients were treated with Pd. All patients were given pegfilgrastim subcutaneously with a single administration performed on the first day of each cycle as primary prophylaxis until the fourth cycle. Results: The median age of the patients was 75 (range 56-85), and the median prior line of therapy was 2 (range 2-6). Seventeen patients (51.5%) had any grade of neutropenia and 20 (60.6%) had any grade of thrombocytopenia before starting pomalidomide treatment. During the 4 cycles of treatment, grade 3 or more neutropenia occurred in 17 patients (51.5%), and 4 (12.1%) experienced grade 3 or more febrile neutropenia. Grade 3 or more infections occurred in 5 patients (15.2%). Interestingly, the patients with markedly increased ANC of more than 2 x 109/L compared to baseline ANC after 7 days of pegfilgrastim at 1st cycle of treatment showed a significantly lower incidence of grade 3-4 neutropenia. The most common adverse event of pegfilgrastim was fatigue, and all the adverse events caused by pegfilgrastim were grade 1 or 2. And there was no significant change in the immune cell population and cytokines during the administration of pegfilgrastim. Discussion: Considering that this study included elderly patients with baseline neutropenia, pegylated G-CSF could be helpful to prevent severe neutropenia, febrile neutropenia, or infection in patients with RRMM.

Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. METHODS: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled. RESULTS: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. CONCLUSION: These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Real-world data of long-term survival in patients with T-cell lymphoma who underwent stem cell transplantation.

This study aimed to identify the benefits of autologous-stem cell transplantation (auto-SCT) and allogeneic-SCT (allo-SCT) in patients with aggressive T-cell lymphomas to aid in the selection of transplantation type in clinical practice. This study retrospectively analyzed data from 598 patients who underwent transplantation for T-cell lymphomas from 2010 to 2020. In total, 317 patients underwent up-front SCT as consolidation therapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 68.7% and 76.1%, respectively. Patients who underwent auto-SCT had significantly better OS (p = 0.026) than those who underwent allo-SCT; however, no statistical difference in PFS was found. Transplantation was used as a salvage therapy in 188 patients who had relapsed/refractory disease. Overall, 96 (51.1%) patients underwent auto-SCT and 92 (48.9%) patients underwent allo-SCT. Auto-SCT improved long-term survival in patients with complete remission (CR). Allo-SCT demonstrated better 3-year PFS in patients with partial remission and relapsed/refractory disease status. However, >50% of patients died within 1 year of allo-SCT. As a consolidative therapy, up-front auto-SCT demonstrated a survival benefit. Auto-SCT was also effective in patients who achieved CR after salvage therapy. If the disease persists or cannot be controlled, allo-SCT may be considered with reduced intensity conditioning.

Effectiveness of pegfilgrastim prophylaxis in preventing febrile neutropenia during R-FC chemoimmunotherapy for chronic lymphocytic leukemia: A multicenter prospective phase II study.

Background: A chemotherapy of rituximab, fludarabine and cyclophosphamide (R-FC) has been accepted as a promising frontline chemotherapy in selected patients with chronic lymphocytic leukemia (CLL). Although R-FC regimen is a relatively dose-dense regimen and neutropenia incidence is more than 50%, primary prophylactic pegfilgrastim was not fully recommended in the clinical field. Therefore, the study evaluated the prophylactic effectiveness of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-FC of patients with CLL. Patients and methods: A single-arm, multicenter, prospective phase II study was designed to assess the efficacy of prophylactic pegfilgrastim. Thirty-four CLL patients were enrolled and analyzed for neutropenia and other related factors, and comparative analysis was performed with historical cohort. Results: Compared with our historical cohort, incidence of grade 3-4 neutropenia and febrile neutropenia was remarkably reduced during any cycle of chemotherapy (14.7% vs. 48.2% of study cohort vs. historical cohort during C1, 5.9% vs. 65.8% during C2, 12.9% vs. 80.6% during C3, 10% vs. 84.6% during C4, 3.4% vs. 83.6% during C5, and 10.7% vs. 85.7% during C6, p <0.001). Also, cumulative incidence of disrupted chemotherapy was noticeably reduced in study cohort on any cycles of R-FC regimen (8.8% vs. 22.2% of study cohort vs. historical cohort on C2, 9.7% vs. 25.2% on C3, 13.4% vs. 26.9% on C4, 13.8% vs. 45.2% on C5, 17.9% vs. 47.3% on C6, p=0.007). In addition, treatment-related mortality was 5.9%, which significantly reduced compared to 9.6% of our historical cohort (HR 0.64, 95% CI 0.42-0.79, P = 0.032). Conclusion: Primary prophylactic pegfilgrastim is effective in the prevention of neutropenia/febrile neutropenia, and infection-related mortality during R-FC regimen in patients with CLL.

Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study.

PURPOSE: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. RESULTS: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). CONCLUSION: Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Ultrasound-guided percutaneous core needle biopsy of abdominal subcutaneous fat for diagnosing amyloidosis: comparison with bone marrow biopsy.

BACKGROUND: Patients with underlying hematologic malignancy have a higher risk of developing systemic amyloidosis, which worsens their prognosis. Histopathologic detection of amyloid deposits in tissue biopsy specimens is the only diagnostic method for amyloidosis. PURPOSE: To compare the efficacy of ultrasound-guided percutaneous core needle biopsy (USPCB) of abdominal subcutaneous fat with that of bone marrow biopsy (BMB) for diagnosing amyloidosis. MATERIAL AND METHODS: A total of 90 consecutive patients with underlying hematologic disorders who underwent both USPCB of abdominal subcutaneous fat and BMB for suspicion of amyloid deposition during a 10-year period were included in this retrospective study. RESULTS: The sensitivity and specificity of detecting amyloid deposition were 85.7% and 100%, respectively, with USPCB as opposed to 4.8% and 100%, respectively, with BMB, and the sensitivity was significantly higher with USPCB (P < 0.001). The mean number of times USPCB was performed was 3.3. There were no major complications associated with USPCB. The sensitivity of detecting amyloidosis was not different between the 18-G needle group and the 14-G group (100% vs. 80%; P = 0.623). Logistic regression analysis revealed that acquiring more cores from USPCB and thinner fat tissues were statistically significant factors that affected the diagnostic accuracy of USPCB for amyloid detection. CONCLUSION: The sensitivity of amyloid deposition was significantly higher with USPCB of abdominal subcutaneous fat than BMB. Acquiring more cores by multiple biopsies instead of using a larger bore needle and thin subcutaneous fat pad may be a favorable factor for the diagnostic accuracy of USPCB.

A Prospective Study of Preemptive Tenofovir Disoproxil Fumarate Therapy in HBsAg-Positive Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

INTRODUCTION: This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. METHODS: We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. RESULTS: No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). DISCUSSION: Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).

Prognostic value of modified criteria for hydroxyurea resistance or intolerance in patients with high-risk essential thrombocythemia.

BACKGROUND: Recognizing intolerance or resistance to hydroxyurea (HU), which is related to the high risk of a disease transformation and reduced survival in essential thrombocythemia (ET), is crucial to making a reasonable decision about second-line therapy. We assessed the prognostic impact of the modified European LeukemiaNet (mELN) criteria used in a recent MAJIC-ET trial by analyzing the incidence of resistance or intolerance to HU and the survival outcome compared with those of the ELN criteria. METHODS: We retrospectively compared the development of HU resistance or intolerance according to the ELN and mELN criteria for 148 high-risk ET patients receiving HU between 2014 and 2018. The maximum tolerated dose for defining HU resistance was used in the mELN criteria. RESULTS: The median age of patients was 65 years (range, 36-87), with a median follow-up of 3.6 years (range, 1.1-6.4). Two thromboembolic events were observed during HU treatment. When applying the ELN criteria, 10 patients (6.9%) were resistant (n = 5 [3.4%]) or intolerant (n = 5 [3.4%]) to HU in comparison with 22 patients (15%, 14 [9.8%]) resistant and 8 [5.5%] intolerant when applying the mELN criteria. Transformation to myelofibrosis and acute myeloid leukemia occurred in 2 (1.4%) patients and 1 (0.7%) patient, respectively, as defined by the ELN criteria compared with 3 (2.1%) and 2 (1.4%) patients as defined by the mELN criteria. In multivariate analysis of transformation-free survival, HU resistance defined by the mELN criteria but not the ELN criteria was an independent prognostic factor. In addition, HU resistance as defined by both sets of criteria was an independent risk factor for inferior overall survival. Intolerance of HU did not have any prognostic impact on survival. CONCLUSIONS: The mELN criteria are useful for identifying high-risk ET patients who might be eligible for second-line therapy in practice, which should be validated in a prospective setting.

Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) as Conditioning Therapy for Autologous Stem Cell Transplantation in Patients with Relapsed or High-Risk Non-Hodgkin's Lymphoma: A Multicenter Randomized Phase II Study bythe Consortium for Improving Survival of Lymphoma (CISL).

PURPOSE: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin's lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. MATERIALS AND METHODS: Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days -7, -6, and -5, etoposide (400 mg/m2 intravenously) on days -5 and -4, and melphalan (50 mg/m2/day intravenously) on days -3 and -2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days -7, -6, and -5, etoposide (400 mg/m2/day intravenously) on days -5 and -4, and cyclophosphamide (50 mg/kg/day intravenously) on days -3 and -2. The primary endpoint was 2-year progression-free survival (PFS). RESULTS: Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. CONCLUSION: There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

A multicenter, open-label study for efficacy and safety evaluation of anagrelide in patients with treatment-naïve, high-risk essential thrombocythemia as a primary treatment.

As the discussion of first-line anagrelide treatment is ongoing, we aimed to prospectively examine the efficacy and safety of anagrelide in cytoreduction therapy-naïve high risk essential thrombocythemia (ET) patients in Korea. Seventy patients from 12 centers were treated with anagrelide monotherapy for up to 8 weeks, followed up until 24 months. At week 8, 50.0% of the patients were able to achieve platelet < 600 x 109/L, and by 12 months, 55/70 (78.6%) patients stayed on anagrelide, and 40.0% patients showed platelet normalization. 14 patients required additional hydroxyurea (HU) for cytoreduction. The median daily dose of needed HU was 500mg (range 250mg - 1500mg). The efficacy was independent of the somatic mutation status. There were 4 thromboembolic events and 7 bleeding events during the follow-up period. The most common adverse events associated with anagrelide use were headache, followed by palpitation/chest discomfort, edema and generalized weakness/fatigue. 7 patients wished to discontinue anagrelide treatment due to adverse events (3 due to headache; 2 due to edema; 1 due to palpitation and 1 due to skin eruption). All in all, first-line anagrelide treatment showed a favorable response with tolerable safety profiles regardless of somatic mutation status.

Optimal timing of treatment at relapse after autologous stem cell transplantation in patients with multiple myeloma: a study of the Korean Multiple Myeloma Working Party (KMM-1909).

The effectiveness of early treatment for biochemical relapse of multiple myeloma (MM) is unclear. To clarify this issue, this retrospective study was performed to evaluate the survival outcomes of 315 patients with relapsed MM after upfront autologous stem cell transplantation (ASCT). Over a median follow-up of 66.6 months (range, 15.1-195.5 months), 48.2% of patients showed biochemical relapse, 41.3% showed clinical relapse, and 10.5% showed significant biochemical relapse. Progression-free survival (PFS) and overall survival (OS) were inferior for patients with clinical relapse compared to the other patients. Multivariate analysis showed that clinical relapse was an independent prognostic factor for OS. In patients with biochemical relapse, there was no significant difference in survival between patients treated while asymptomatic and those treated once clinical symptoms had appeared. Relapse type after upfront ASCT was a significant prognostic factor in patients with MM. In addition, no survival benefit of early treatment at biochemical relapse was observed, but a triplet regimen may be beneficial for MM patients with biochemical relapse.

Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia.

BACKGROUND/AIMS: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. RESULTS: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. CONCLUSION: Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Real-World Outcomes of Ruxolitinib in Patients With Myelofibrosis Focusing on Red Blood Cell Transfusion: A Multicenter Study From the MPN Working Party of the Korean Society of Hematology.

INTRODUCTION/BACKGROUND: Ruxolitinib is an established treatment for myelofibrosis (MF) that has demonstrated clinical benefit by reducing spleen size and debilitating MF-related symptoms. However, despite the efficacy of ruxolitinib, anemia remains a major adverse event that causes dose modification or discontinuation in real-world practice. Additionally, dependence on red blood cell (RBC) transfusion (TF) is common during treatment; therefore, we explored the outcome of ruxolitinib therapy with a primary focus on RBC TF. PATIENTS/METHODS: We retrospectively reviewed the medical records of 123 MF patients treated with ruxolitinib between January 2012 and April 2020 at eight academic centers in Korea. RESULTS: At ruxolitinib initiation, 38 patients (30.9%) underwent ≥ 2 units of RBC TF over 8 weeks. The most common reason for permanent discontinuation was intolerant anemia (10/63, 15.9%). The most common reasons for temporary interruption were nonhematologic toxicity (26/55, 21.1%), anemia (23/55, 18.7%) and thrombocytopenia (13/55, 10.6%). Among the 123 patients in the study, 57 (46.3%), 42 (34.1%), and 40 patients (32.5%) who were receiving or stopped ruxolitinib therapy had a status of RBC TF dependence, long-term RBC TF dependence, or severe RBC TF dependence, respectively. The presence of ≥ 2 units of RBC transfusion over 8 weeks at ruxolitinib initiation was an independent risk factor for persistent RBC TF dependence. CONCLUSION: The requirement for RBC TF is commonly encountered during treatment of MF with ruxolitinib, particularly among those with pre-existing ≥ 2 units of RBC TF over 8 weeks. For those patients, overcoming the barrier of maintenance TF is demanding.