Changing the strategic paradigm for the treatment of adult acute myeloid leukemia

Acute myeloid leukemia (AML) is a representative blood cancer, accounting for most adult leukemia cases in Korea. Until recently, intensive chemotherapy and hematopoietic stem cell transplantation were the only curative treatment options for AML. However, the recent introduction of new drugs is bringing about changes in the strategic paradigm for the treatment of AML.Current Concepts: Along with the clinical eligibility for receiving intensive treatment and hematopoietic stem cell transplantation, the most critical determinants in treating AML are precise classification and risk stratification based on cytogenetic and molecular information. The recently revised World Health Organization classification, newly proposed International Consensus Classification, and the latest version of the European LeukemiaNet risk stratification reflect the importance of cytogenetic and molecular information. Although there have been no significant changes for a long time in the landscape of AML, especially in the field of treatment, the treatment paradigm has started to evolve with the introduction of new drugs. This evolution is led by FLT3 inhibitors, Bcl-2 inhibitors, isocitrate dehydrogenase inhibitors, target agents against CD33 antigens, and liposomal formulations of chemotherapeutics.Discussion and Conclusion: Successful initial treatment to induce complete remission followed by post-remission treatment to remove residual disease can lead to the achievement of long-term survival and cure goals in AML. We hope that new drugs will markedly improve the treatment outcomes for patients with AML.

Predictive Factors of Event-Free Survival at 24 Months in Patients with Peripheral T-Cell Lymphoma: A Retrospective Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24. @*Materials and Methods@#Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24. @*Results@#Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001). @*Conclusion@#Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea

Background@#Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. @*Methods@#An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. @*Results@#During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). @*Conclusion@#This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

Different roles of surveillance positron emission tomography according to the histologic subtype of non-Hodgkin’s lymphoma

Background/Aims@#Although the use of surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is discouraged in patients with diffuse large B-cell lymphoma, its usefulness in different subtypes has not been thoroughly investigated. @*Methods@#We retrospectively evaluated 157 patients who showed positive results on surveillance FDG-PET/CT every 6 months following complete response for up to 5 years. All of the patients also underwent biopsies. @*Results@#Seventy-eight (49.6%) of 157 patients had true positive results; the remaining 79 (50.3%), including eight (5.1%) with secondary malignancies, were confirmed to yield false positive results. Among the 78 patients with true positive results, the disease in seven (8.9%) had transformed to a different subtype. The positive predictive value (PPV) of FDG-PET/CT for aggressive B-cell non-Hodgkin’s lymphoma (NHL) was lower than that for indolent B-cell or aggressive T-cell NHL (p = 0.003 and p = 0.018, respectively), especially in patients with a low/low-intermediate international prognostic index (IPI) upon a positive PET/CT finding. On the other hand, indolent B-cell and aggressive T-cell NHL patients showed PPVs of > 60%, including those with low/low-intermediate secondary IPIs. @*Conclusions@#The role of FDG-PET/CT surveillance is limited, and differs according to the lymphoma subtype. FDG-PET/CT may be useful in detecting early relapse in patients with aggressive T-cell NHL, including those with low/low-intermediate risk secondary IPI; as already known, FDG-PET/CT has no role in aggressive B-cell NHL. Repeat biopsy should be performed to discriminate relapse or transformation from false positive findings in patients with positive surveillance FDG-PET/CT results.

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Background/Aims@#Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. @*Methods@#We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. @*Results@#Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). @*Conclusions@#Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

All-Trans Retinoic Acid Synergizes with Enasidenib to Induce Differentiation of IDH2-Mutant Acute Myeloid Leukemia Cells

Purpose@#Pharmacological inhibition of mutant isocitrate dehydrogenase (IDH) reduces R-2-hydroxyglutarate (2-HG) levels and restores cellular differentiation in vivo and in vitro. The IDH2 inhibitor enasidenib (AG-221) has been approved by the FDA as a first-in-class inhibitor for the treatment of relapsed or refractory (R/R) IDH2-mutant acute myeloid leukemia (AML). In this study,the effects of a combination of all-trans retinoic acid (ATRA) and AG-221 on AML cell differentiation was explored, along with the mechanisms employed by IDH2-mutant cells in AML. Materials and Methods: We treated the human AML cell line, IDH2-mutant-TF-1, and primary human AML cells carrying IDH2 mutation with 30 μM AG-221 and 100 nM ATRA, alone or in combination. @*Results@#Combined treatment with AG-221 and ATRA inhibited 2-HG production and resulted in synergistic effects on differentiation among IDH2-mutant AML cells and primary AML cells expressing IDH2 mutation. Combined treatment with AG-221 and ATRA altered autophagic activity. AG-221 and ATRA treatment-induced differentiation of IDH2-mutant AML cells was associated with autophagy induction, without suppressing autophagy flux at maturation and degradation stages. A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment. @*Conclusion@#Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.

HBsAg-Negative, Anti-HBc–Negative Patients Still Have a Risk of Hepatitis B Virus–Related Hepatitis after Autologous Stem Cell Transplantation for Multiple Myeloma or Malignant Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although hepatitis B surface antigen (HBsAg)–negative, hepatitis B core antibody (anti-HBc)–negative patients are not considered to be at risk for hepatitis B virus (HBV)–related hepatitis, the actual risk remains to be elucidated. This study aimed to evaluate the risk of HBV-related hepatitis in HBsAg-negative, anti-HBc–negative patients receiving autologous stem cell transplantation (ASCT) for multiple myeloma (MM) or malignant lymphoma. MATERIALS AND METHODS: We retrospectively reviewed data from 271 HBsAg-negative patients (161 anti-HBc–negative and 110 anti-HBc–positive at the time of ASCT) who received ASCT for MM or lymphoma. The risk of HBV-related hepatitis was analyzed according to the presence of anti-HBc. HBV serology results at the time of ASCT were compared with those at the time of diagnosis of MM or lymphoma. RESULTS: Three patients (two anti-HBc–negative MMs and one anti-HBc–positive MM) developed HBV-related hepatitis after ASCT. The rate of HBV-related hepatitis did not differ among patients with or without anti-HBc status (p=0.843). HBV-related hepatitis more frequently occurred in MM patients than in lymphoma patients (p=0.041). Overall, 9.1% of patients (16.7% with MM and 5.4% with lymphoma) who were HBsAg–negative and anti-HBc–positive at the time of diagnosis had lost anti-HBc positivity during chemotherapy prior to ASCT. CONCLUSION: Our data suggest that HBsAg-negative, anti-HBc–negative patients at the time of ASCT for MM or lymphoma still might be at a risk for HBV-related hepatitis.

Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.

Factors associated with pulmonary toxicity after myeloablative conditioning using fractionated total body irradiation

PURPOSE: Pulmonary toxicities, including infectious pneumonia (IP) and idiopathic pneumonia syndrome (IPS), are serious side effects of total body irradiation (TBI) used for myeloablative conditioning. This study aimed to evaluate clinical factors associated with IP and IPS following TBI. MATERIALS AND METHODS: Fifty-eight patients with hematologic malignancies who underwent TBI before allogeneic hematopoietic stem cell transplantation between 2005 and 2014 were reviewed. Most patients (91%) received 12 Gy in 1.5 Gy fractions twice a day. Pulmonary toxicities were diagnosed based on either radiographic evidence or reduced pulmonary function, and were subdivided into IP and IPS based on the presence or absence of concurrent infection. RESULTS: Pulmonary toxicities developed in 36 patients (62%); 16 (28%) had IP and 20 (34%) had IPS. IP was significantly associated with increased treatment-related mortality (p = 0.028) and decreased survival (p = 0.039). Multivariate analysis revealed that the risk of developing IPS was significantly higher in patients who received stem cells from a matched unrelated donor than from a matched sibling donor (p = 0.021; hazard ratio [HR] = 12.67; 95% confidence interval [CI], 1.46–110.30). Combining other conditioning agents with cyclophosphamide produced a higher tendency to develop IP (p = 0.064; HR = 6.19; 95% CI, 0.90–42.56). CONCLUSION: IP and IPS involve different risk factors and distinct pathogeneses that should be considered when planning treatments before and after TBI.

Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia

PURPOSE: Decitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML. MATERIALS AND METHODS: Twenty-four patients with AML who received at least one course of decitabine (20 mg/m²/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively. RESULTS: The median age of the patients was 73.5 years. The longest follow-up duration was 502 days. A total of 113 cycles of treatment were given to 24 patients, and the median number of cycles was four (range, 1–14). Thirteen patients dropped out because of death, no or loss of response, patient refusal, or transfer to another hospital. Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles, respectively, and responses to treatment were evaluated in 17. A complete response (CR) or CR with incomplete blood-count recovery was achieved in six (35.3%) patients, and the estimated median overall survival was 502 days. Ten patients developed grade >2 hematologic or non-hematologic toxicities. In univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin level, and bone marrow iron were significantly associated with response to decitabine. CONCLUSION: Five-day decitabine treatment showed acceptable efficacy in older patients with AML who are unfit for conventional chemotherapy, with a CR rate 35.3% and about a median overall survival of 18 months.

Clinical characteristics and treatment outcomes of isolated myeloid sarcoma without bone marrow involvement: a single-institution experience

BACKGROUND: Isolated myeloid sarcoma (MS) is a rare extramedullary tumor mass composed of malignant myeloid precursor cells without any evidence of leukemia in the peripheral blood and bone marrow. We describe the clinical characteristics and outcomes of patients diagnosed with isolated MS at our institution. METHODS: We retrospectively reviewed 9 of 497 acute myeloid leukemia (AML) patients (1.8%) with isolated MS. Isolated MS patients were divided into 2 groups according to the first-line treatment strategy: systemic treatment only (S) or local treatment with or without systemic treatment (LS). RESULTS: The most common site of MS occurrence was the head and neck area (N=4, 44.4%), followed by the anterior mediastinum (N=2, 22.2%) and the gastrointestinal tract (N=2, 22.2%). The tumors of 4 patients (44.4%) eventually evolved to AML, in a median time of 13.4 months (range, 2.4–20.1 mo). The number of patients achieving complete remission after first-line treatment was higher in the LS group (N=5, 83.3%) than in the S group (N=1, 33.3%) (P =0.226). All patients in the LS group survived, but those in the S group died (P=0.012). CONCLUSION: Accurate and rapid diagnosis using various modalities and the early initiation of intensive combined treatment may be the optimal strategies to reduce the risk of isolated MS subsequently evolving to AML. To fully understand the characteristics of isolated MS, a larger number of patients from a multinational study is necessary.

The Clinical Significance of Implementing Concurrent Direct Antiglobulin Test and Antibody Elution Test in Diagnosing Hemolytic Disease of the Fetus and Newborn / 대한수혈학회지

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) is a condition in which immune hemolytic anemia occurs in fetuses or newborns as a result of maternal alloimunized antibodies transfer. Antibody elution test and direct antiglobulin test (DAT) can be performed to diagnose HDFN; maternal originated antibodies cannot be confirmed if DAT is utilized alone. In this study, we analyzed the clinical significance of implementing concurrent DAT and antibody elution test in diagnosing HDFN. METHODS: We retrospectively analyzed the DATs and antibody elution tests that were simultaneously conducted in a period of 11 years, between 2005 and 2015, in newborns that received hemoglobin, reticulocyte, and total bilirubin tests. According to the results of these tests, the number of newborns diagnosed with HDFN was measured. Furthermore, the sensitivity and specificity of DAT and antibody elution test were compared. RESULTS: Among 325 newborns, the results of DATs and antibody elution tests were both negative in 208 (64.0%), negative and positive, respectively, in 80 (24.6%), positive and negative in 10 (3.1%), both positive in 27 (8.3%). When this was compared to the clinical diagnosis of HDFN, more sensitive and specific diagnoses were possible when implementing DAT and antibody elution test together (sensitivity of 76.9% for antibody elution test and specificity of 90.3% for DAT). Twenty-six (8.0%) newborns suspected for HDFN showed clinically significant hemolytic anemia. CONCLUSION: It is necessary to conduct both DAT and antibody elution test when HDFN is suspected. The severity of hemolysis in HDFN can be indirectly anticipated using an antibody elution test confirming maternal originated alloantibodies.

Pretreatment Lymphopenia, Poor Performance Status, and Early Courses of Therapy Are Risk Factors for Severe Bacterial Infection in Patients with Multiple Myeloma during Treatment with Bortezomib-based Regimens

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.

Chronic Myeloid Leukemia With Rare Variant b2a3 (e13a3) BCR-ABL1 Fusion

No abstract available.

Prediction of survival by applying current prognostic models in diffuse large B-cell lymphoma treated with R-CHOP followed by autologous transplantation

BACKGROUND: Among the currently available prognostic models for diffuse large B-cell lymphoma (DLBCL), we investigated to determine which is most adoptable for DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by upfront autologous stem cell transplantation (auto-SCT). METHODS: We retrospectively evaluated survival differences among risk groups based on the International Prognostic Index (IPI), the age-adjusted IPI (aaIPI), the revised IPI (R-IPI), and the National Comprehensive Cancer Network IPI (NCCN-IPI) at diagnosis in 63 CD20-positive DLBCL patients treated with R-CHOP followed by upfront auto-SCT. RESULTS: At the time of auto-SCT, 74.6% and 25.4% of patients had achieved complete remission and partial remission after R-CHOP, respectively. As a whole, the 5-year overall (OS) and progression-free survival (PFS) rates were 78.8% and 74.2%, respectively. The 5-year OS and PFS rates according to the IPI, aaIPI, R-IPI, and NCCN-IPI did not significantly differ among the risk groups for each prognostic model (P-values for OS: 0.255, 0.337, 0.881, and 0.803, respectively; P-values for PFS: 0.177, 0.904, 0.295, and 0.609, respectively). CONCLUSION: There was no ideal prognostic model among those currently available for CD20-positive DLBCL patients treated with R-CHOP followed by upfront auto-SCT.

Fatal PTLD Accompanied by Rapid Lymphocyte Proliferation in the Early Phase of Allogeneic HSCT / 대한내과학회지

Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of clinically and morphologically heterogeneous lymphoid proliferations of various clonal compositions that are observed after hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. The majority of PTLD cases are associated with Epstein-Barr virus (EBV) infection, while overt peripheral blood (PB) or bone marrow (BM) involvement in PTLD is uncommon in early lesions. We report a 38-year-old woman with EBV-related PTLD, with BM and PB involvement, who presented with peripheral lymphocytosis as an early lesion 1 month after haploidentical HSCT for Philadelphia chromosome-positive acute lymphoblastic leukemia was performed during first complete remission. Although PB or BM involvement of PTLD after HSCT is uncommon in early lesions, peripheral lymphocytosis can be an initial presenting manifestation of PTLD, as in this case.

Hemophagocytic Lymphohistiocytosis after Lung Transplantation / 대한구급학회지

Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal complication after solid organ transplantation. Acquired forms of HLH are described in association with severe sepsis, autoimmune disorders, malignancy, immune-compromised states, infections, and solid organ transplantation. We experienced a case of hemophagocytic lymphohistiocytosis after bilateral lung transplantation. Leukopenia, thrombocytopenia, and hyperbilirubinemia were noted and became aggravated 50 days after transplantation. Diagnosis of HLH was based on clinical and laboratory findings of splenomegaly, cytopenia, elevated ferritin, elevated interleukin-2 receptor, and hemophagocytosis in bone marrow. Other features such as elevated bilirubin, lactate dehydrogenase, and D-dimer which can be present in HLH were also noted. The patient was immediately treated with etoposide and dexamethasone. Despite aggressive therapy, the patient deteriorated and died. Awareness of the diagnostic criteria of HLH after lung transplantation is important for clinicians.

Radiotherapy as an effective treatment modality for follicular lymphoma: a single institution experience

PURPOSE: Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma that is highly sensitive to radiotherapy (RT). However, the effectiveness of RT has not been well established. We reviewed our experiences to assess the role of RT for FL and analyze treatment results. MATERIALS AND METHODS: Retrospective analysis was done on 29 patients who received first RT between January 2003 and August 2013. Of 23 early stage (stage I, II) patients, 16 received RT alone, four received chemotherapy followed by RT, two received RT postoperatively, and one received salvage RT for relapse after resection. Six advanced-stage (stage III, IV) patients received RT after chemotherapy: two received consolidation RT, three received salvage RT for residual lesions, and one received RT for progressive sites. Median RT dose was 30.6 Gy (range, 21.6 to 48.6 Gy). Median follow-up duration was 62 months (range, 6 to 141 months). RESULTS: All patients showed complete response in the radiation field. Eight outfield relapses were reported. Seven patients received salvage treatment (three chemotherapy, four RT). Four patients showed excellent responses, especially to RT. Estimated 5-year and 10-year relapse-free survivals were 72% and 60%. In the RT-alone group, 5-year relapse-free survival was 74.5%. All advanced-stage patients were disease-free with 100% 5-year overall survival. Disease-specific death was noted in only one patient; four others died of other unrelated causes. No significant toxicity was reported. CONCLUSION: RT resulted in excellent treatment outcomes for all FL stages when used as a primary treatment modality for early stage or salvage-treatment modality for advanced-stage disease.

Korean Guidelines for Treating Chronic Myelogenous Leukemia - The Korean Society of Hematology Chronic Myelogenous Leukemia Working Party / 대한내과학회지

BACKGROUND/AIMS: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs). METHODS: New guidelines were developed in 2012 based on the results of a survey and a consensus meeting of various Korean experts, the reports of recent clinical studies, and updated guidelines from external study groups. RESULTS: An assessment of risk factors is strongly recommended before treating newly diagnosed chronic phase CML. Imatinib, dasatinib, and nilotinib are reimbursable in Korea as first-line treatments, and the patient's age, comorbidities, and possible adverse events should be considered in the choice of treatment. Molecular studies are recommended for assessing treatment efficacy instead of invasive cytogenetic response evaluations, and an early response is believed to correlate with a good prognosis. Second-line TKIs can be considered for patients who fail or are intolerant of first-line therapy, pending analysis of ABL tyrosine kinase mutation status. For treating advanced stages, a combination of TKIs with cytotoxic agents and hematopoietic cell transplantation is recommended. The adverse effects of TKI therapy can be managed via dose reduction and supportive care, or switching to an alternate TKI. CONCLUSIONS: The use of TKIs has improved the outcome of CML treatment. Treatment-free remission after discontinuing TKIs might be possible in select patients who achieve sufficient response, indicating that curative treatment for CML can be expected in the future.

Hemophagocytic Lymphohistiocytosis after Lung Transplantation / 대한중환자의학회지

Hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal complication after solid organ transplantation. Acquired forms of HLH are described in association with severe sepsis, autoimmune disorders, malignancy, immune-compromised states, infections, and solid organ transplantation. We experienced a case of hemophagocytic lymphohistiocytosis after bilateral lung transplantation. Leukopenia, thrombocytopenia, and hyperbilirubinemia were noted and became aggravated 50 days after transplantation. Diagnosis of HLH was based on clinical and laboratory findings of splenomegaly, cytopenia, elevated ferritin, elevated interleukin-2 receptor, and hemophagocytosis in bone marrow. Other features such as elevated bilirubin, lactate dehydrogenase, and D-dimer which can be present in HLH were also noted. The patient was immediately treated with etoposide and dexamethasone. Despite aggressive therapy, the patient deteriorated and died. Awareness of the diagnostic criteria of HLH after lung transplantation is important for clinicians.