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 / Journal of the Korean Cancer Association, 대한암학회지

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.

Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma

Background/Aims@#Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. @*Methods@#Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). @*Results@#Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). @*Conclusions@#Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Recent advances in the management of immune-mediated thrombotic thrombocytopenic purpura

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially life-threatening thrombotic microangiopathy caused by autoantibody-mediated severe ADAMTS13 deficiency. TTP should be suspected in patients with microangiopathic hemolytic anemia and thrombocytopenia without a definite cause. Early detection of iTTP and prompt treatment with plasma exchange and corticosteroids are essential. Rituximab administration should be considered for refractory or relapsed iTTP, and can be used as a first-line adjuvant or preemptive therapy. Treatment with caplacizumab, a novel anti-von Willebrand factor nanobody, resulted in a faster time to platelet count response, significant reduction in iTTP-related deaths, and reduced incidence of refractory iTTP. TTP survivors showed a higher rate of chronic morbidities, including cardiovascular disease and neurocognitive impairment, which can lead to a poor quality of life and higher mortality rate. Meticulous long-term follow-up of TTP survivors is crucial.

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. @*Conclusions@#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.

Clinical features and outcomes of JAK2V617F-positive polycythemia vera and essential thrombocythemia according to the JAK2V617F allele burden

Background@#JAK2mutation status is a well-known risk factor for thrombosis in patients with myeloproliferative neoplasms. However, the clinical usefulness of JAK2V617F allele burden is under investigation. @*Methods@#We retrospectively evaluated the impact of the JAK2V617F allele burden on clinical characteristics and outcomes of JAK2V617F-positive polycythemia vera (PV) and essential thrombocythemia (ET). The JAK2V617F allele burden was measured using sequencing. @*Results@#Altogether, 127 patients with JAK2V617F mutation (PV, N=61; ET, N=66) were included in this study. JAK2V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8-year OS based on the JAK2V617F allele burden was not significant. @*Conclusion@#The JAK2V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2V617F-positive PV and ET.

The 2020 revision of the guidelines for the management of myeloproliferative neoplasms

In 2016, the World Health Organization revised the diagnostic criteria for myeloproliferative neoplasms (MPNs) based on the discovery of disease-driving genetic aberrations and extensive analysis of the clinical characteristics of patients with MPNs. Recent studies have suggested that additional somatic mutations have a clinical impact on the prognosis of patients harboring these genetic abnormalities. Treatment strategies have also advanced with the introduction of JAK inhibitors, one of which has been approved for the treatment of patients with myelofibrosis and those with hydroxyurea-resistant or intolerant polycythemia vera. Recently developed drugs aim to elicit hematologic responses, as well as symptomatic and molecular responses, and the response criteria were refined accordingly. Based on these changes, we have revised the guidelines and present the diagnosis, treatment, and risk stratification of MPNs encountered in Korea.

Updated recommendations for the treatment of venous thromboembolism

Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a condition characterized by abnormal blood clot formation in the pulmonary arteries and the deep venous vasculature. It is often serious and sometimes even fatal if not promptly and appropriately treated. Moreover, the later consequences of VTE may result in reduced quality of life. The treatment of VTE depends on various factors, including the type, cause, and patient comorbidities. Furthermore, bleeding may occur as a side effect of VTE treatment. Thus, it is necessary to carefully weigh the benefits versus the risks of VTE treatment and to actively monitor patients undergoing treatment. Asian populations are known to have lower VTE incidences than Western populations, but recent studies have shown an increase in the incidence of VTE in Asia. A variety of treatment options are currently available owing to the introduction of direct oral anticoagulants.The current VTE treatment recommendation is based on evidence from previous studies, but it should be applied with careful consideration of the racial, genetic, and social characteristics in the Korean population.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity

Background@#To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. @*Methods@#Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. @*Results@#A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). @*Conclusion@#Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity

Background@#To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. @*Methods@#Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. @*Results@#A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). @*Conclusion@#Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Myeloid Sarcoma of Peritoneum in Acute Myeloid Leukemia Patient with Inversion of Chromosome 16 / 대한내과학회지

Myeloid sarcoma is an extramedullary myeloid neoplasm that usually involves the skin, soft tissues, and lymph nodes. Myeloid sarcoma is found in 2.5-9.1% of acute myeloid leukemia patients, usually those with t (8;21), while inv (16) is rarely associated with myeloid sarcoma. Consequently, little is known of the characteristics and incidence of inv (16) in myeloid sarcoma. Myeloid sarcoma in acute myeloid leukemia patients with inv (16) is most often found in the abdominal lesions; the intestinal tract is involved most commonly, in the form of a mass. Here, we report an unusual myeloid sarcoma presenting as peritoneal carcinomatosis in acute myeloid leukemia with inv (16) that appeared to be ascites.

A Case of Malignant Melanoma with Zosteriform Skin Metastasis Arising in a Medium-sized Congenital Melanocytic Nevus / 대한피부과학회지

Zosteriform metastasis from malignant melanoma is a rare type of skin metastasis that shows cutaneous lesions including patches, plaques, and nodules along with dermatomes, and thus needs to be distinguished from herpes zoster skin infection. Although some authors have explained the mechanism of zosteriform metastasis, its pathogenesis remains unknown. Herein, we describe an 85-year-old woman with zosteriform metastasis of malignant melanoma arising in a medium-sized congenital melanocytic nevus.

POEMS syndrome misdiagnosed as bone metastasis in a patient with thyroid cancer / 영남의대학술지

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a monoclonal plasma cell disorder. Patients with POEMS syndrome also have various clinical manifestations including generalized edema, pleural effusion, ascites, papilledema, and sclerotic bone lesions. These manifestations can lead to a misdiagnosis or delayed diagnosis. We recently experienced a 51-year-old male patient with POEMS syndrome whose sclerotic bone lesion was misdiagnosed as malignant bone metastasis of papillary thyroid carcinoma. We reassessed the patient and found polyneuropathy, hepatosplenomegaly, hypothyroidism, partial hypopituitarism, immunoglobulin G lambda-type monoclonal gammopathy, hypertrichosis, ascites, and multiple sclerotic bone lesions, all of which led us to a diagnosis of POEMS syndrome. Treatment with thalidomide and dexamethasone resulted in clinical and radiological improvement. The patient has remained in remission after peripheral blood stem cell transplantation.

Successful Salvage Treatment for Isolated Brain Parenchymal Relapse due to Diffuse Large B Cell Lymphoma / 대한내과학회지

A central nervous system (CNS) relapse is a rare but mostly fatal complication in patients with diffuse large B cell lymphoma (DLBCL). CNS involvement can occur as an isolated event or can be combined with progression of systemic disease. There are limited data on treatment outcomes of patients with DLBCL and secondary CNS involvement. We report the clinical data, treatments, and outcomes of two DLBCL patients with isolated CNS relapses involving the brain parenchyma. Isolated CNS disease involving the brain parenchyma may be potentially treatable as the initial relapse site after complete remission from systemic treatment.

Prevention of Venous Thromboembolism, 2nd Edition: Korean Society of Thrombosis and Hemostasis Evidence-Based Clinical Practice Guidelines

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.

Relapsed plasmacytoma in central nervous system after complete remission of extramedullary plasmacytoma / 영남의대학술지

Extramedullary plasmacytoma (EMP) is a rare disease that occurs in 3% to 5% of patients with plasma cell disorder. It occurs most commonly in the upper respiratory tract and the oral cavity. Very few EMP cases have been reported in the central nervous system (CNS). We report herein an unusual case of EMP in the nasal cavity that recurred in the CNS without systemic involvement. A 67-year-old man visited our hospital due to a month-long bout with exophthalmos. He was diagnosed with EMP in the nasal cavity, paranasal sinus, and orbital cavity. He received radiotherapy to which he had complete responses. After 2 years, he visited our hospital because of a month-long headache. He was diagnosed with EMP recurrence in the CNS via brain magnetic resonance imaging and cerebrospinal fluid analysis. He was treated with whole brain radiotherapy and intrathecal chemotherapy with methotrexate, but he expired due to pneumonia.

Total extract of Korean red ginseng facilitates human bone marrow hematopoietic colony formation in vitro

BACKGROUND: The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation. METHODS: Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 microg/mL, 100 microg/mL) or Ginsenoside Rg1 (100 microg/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry. RESULTS: The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6x10(7) and 1.3-48x10(7) and 8.9x10(4) and 1.8-80x10(4), respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid. CONCLUSION: Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage.

A case of myelodysplastic syndrome with marked eosinophilia showing favorable prognosis

Myelodysplastic syndrome (MDS) with eosinophilia is a rare condition and has yet to be classified under the 2008 World Health Organization classification. However, reports have described the prognostic significance of chronic persistent eosinophilia in MDS. Here, we report a case of a 67-year-old woman who was admitted to the hospital in July 2007 with generalized weakness, dizziness, and dyspnea on exertion persisting for 5 years. In the initial investigation, eosinophilia (22.1%) in peripheral blood and an increased proportion of eosinophils (5.6%) in normocellular bone marrow with dysplastic megakaryocytes and erythroid cells were noted. Eosinophilia was continuously detected during follow-up over 3 years. In a second bone marrow examination in August 2010, hypercellular bone marrow with similar features was observed. These findings led to the diagnosis of MDS with chronic persistent eosinophilia. To increase awareness of the prognostic significance of MDS with chronic eosinophilia, here we report a slow-progressing case of MDS with chronic persistent eosinophilia lasting over 6 years.

Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell Lymphoma Patients with Bone Marrow Involvement / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy. MATERIALS AND METHODS: A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively. RESULTS: The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate analysis, among total patients, BM involvement showed a significant association with OS and EFS. In univariate and multivariate analyses, even among stage IV patients, a significant association with worse EFS was observed in the BM involvement group. CONCLUSION: BM involvement at diagnosis affected the survival of patients with DLBCL who received RCHOP. Although use of RCHOP can result in significant improvement of the therapeutic effect of DLBCL, BM involvement is still a negative prognostic factor of DLBCL patients in the era of rituximab.

Early Response to Bortezomib Combined Chemotherapy Can Help Predict Survival in Patients with Multiple Myeloma Who Are Ineligible for Stem Cell Transplantation

Novel agents to treat multiple myeloma (MM) have increased complete respone (CR) rates compared with conventional chemotherapy, and the quality of the response to treatment has been correlated with survival. The purpose of our study was to show how of early response to bortezomib combined chemotherapy influences survival in patients with newly diagnosed MM who are ineligible for stem cell transplantation. We assessed patient responses to at least four cycles of bortezomib using the International Myeloma Working Group response criteria. The endpoints were comparisons of progression free survival (PFS) and overall survival (OS) between early good response group (A group) and poor response group (B group). We retrospectively analyzed data from 129 patients registered by the Korean Multiple Myeloma Working Party, a nationwide registration of MM patients. The 3 yr PFS for the A and B groups was 55.6% and 18.4%, respectively (P < 0.001). The 3 yr OS for the A and B groups was 65.3% and 52.9%, respectively (P = 0.078). The early response to at least four cycle of bortezomib before next chemotherapy may help predict PFS in patients with MM who are ineligible stem cell transplantation.