Chan Jeoung Park

Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia

Clinical impact of imatinib was evaluated in 20 patients (median age, 37 years; range, 15–67 years) with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), who were administered with induction chemotherapy of daunorubicin, vincristine, prednisolone, and L-asparaginase, along with imatinib 600u2009mg/day during remission induction and 400u2009mg/day during consolidation courses. One patient died on day 14 from septic shock, while the remaining 19 achieved complete remission (CR). In total, 15 patients underwent allogeneic hematopoietic cell transplantation (HCT) during first CR. After median follow-up period of 799 days, six patients experienced recurrence; two with early recurrence within 100 days, one with leptomeningeal recurrence at 11 month, and three with post-HCT recurrence. Eight patients died. Median CR duration (821 days) and median patient survival (894 days) in the study were significantly longer by 2.9- and 2.3-fold, respectively, when compared to those of 18 historical patients treated with same regimen of combination chemotherapy without imatinib. Toxicities of the combined treatment were manageable and included grade 4 myelosuppression (n=20) and reversible ⩾grade 3 hyperbilirubinemia (n=4). Beneficial clinical effects were observed when imatinib was added to combination chemotherapy in patients with newly diagnosed Ph+ ALL. Further studies with larger number of patients are necessary.

Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome

We retrospectively studied 227 patients with MDS (1) to identify the prognostic factors of survival and acute leukemia evolution in Korean patients with MDS, (2) to apply different prognostic scoring systems to the same group of patients, and (3) to compare the FAB with the WHO classification. Six scoring systems were applied to the patients, and the FAB and WHO classifications were compared. The patients’ median age was 57 years. The median survival time was 21 months, and age, dysgranulopoiesis and the IPSS cytogenetic groups were independent prognostic factors for survival. Acute leukemia occurred in 34 patients, and the cumulative incidence was 27.1% at 3 years. Marrow blast percentage was the only independent prognostic factor for acute leukemia evolution. Most scoring systems successfully discriminated risk groups for survival and acute leukemia evolution, but patient distribution into risk groups varied according to the scoring systems. Refractory cytopenia with multilineage dysplasia and RAEB II seemed to have different prognoses from RA or RARS and RAEB I, respectively. In summary, our MDS patients had different disease natures from those of Western countries regarding clinical features, prognostic factors and cytogenetic profiles. Although the WHO classification seems to improve the FAB classification, further studies are warranted to validate the utility of the WHO classification before it is accepted for routine clinical use. Our study has the limitations of retrospective analysis, and our results should be verified in future prospective studies.

Distribution of lymphoid neoplasms in the Republic of Korea: Analysis of 5318 cases according to the World Health Organization classification†

Compared with the West, the overall incidence of lymphoid neoplasms is lower, and the subtype distribution is distinct in Asia. To comprehensively investigate the subtype distribution with the age and sex factors, and temporal changes of subtype proportions, we re‐assessed all patients with lymphoid neoplasms diagnosed at a large oncology service in the Republic of Korea from 1989 to 2008 using the World Health Organization classifications. Of the total 5,318 patients, 66.9% had mature B‐cell neoplasms, 12.5% had mature T/natural killer (NK)‐cell neoplasms, 16.4% had precursor lymphoblastic leukemia/lymphoma (ALL/LBL), and 4.1% had Hodgkins lymphoma. The most common subtypes were diffuse large B‐cell lymphoma (30.5%), plasma cell myeloma (14.0%), extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue type (MALT lymphoma; 12.4%), B‐cell ALL/LBL (11.3%), Hodgkins lymphoma (4.1%), peripheral T‐cell lymphoma unspecified (4.0%), T‐cell ALL/LBL (3.9%), and extranodal NK/T‐cell lymphoma of nasal type (3.9%). Most subtypes showed male predominance, with an average M/F ratio of 1.3. Most mature lymphoid neoplasms were diseases of adults (mean age, 53.5 yr), whereas ALL/LBLs were of young individuals (mean age, 20.3 yr). When the relative proportion of subtypes were compared between two decades (1989–1998 vs. 1999–2008), especially MALT lymphoma has increased in proportion, whereas T/NK‐cell neoplasms and ALL/LBL have slightly decreased. In summary, the lymphoid neoplasms of Koreans shared some epidemiologic features similar to those of other countries, whereas some subtypes showed distinct features. Although the increase in incidence of lymphoid neoplasms is relatively modest in Korea, recent increase of MALT lymphoma and decrease of T/NK‐cell neoplasms and ALL/LBL are interesting findings. Am. J. Hematol., 2010.

Clinical features of adult patients with secondary hemophagocytic lymphohistiocytosis from causes other than lymphoma: an analysis of treatment outcome and prognostic factors

Although hemophagocytic syndrome (HS) featuring secondary hemophagocytic lymphohistiocytosis (HLH) has a grave prognosis, little is known about the natural course of the disease. Patients who showed the clinical features of HLH as well as tissue-proven hemophagocytosis when seen at Asan Medical Center between 1999 and 2010 were included in this analysis. Patients with proven lymphoma were excluded. The median age of our 23 study patients was 49xa0years. Epstein–Barr virus was suspected to have caused HS in 16 (70%) patients and hepatitis A virus in one patient. Twenty-two patients were treated, 13 according to the HLH protocol and nine using immunosuppressive agents such as corticosteroid and/or cyclosporine. Five patients undertook allogeneic hematopoietic cell transplantation (HCT) during their treatment-dependent relapse (nu2009=u20094) or responsive status (nu2009=u20091). After the median follow-up of 180xa0days, 17 (74%) died and six (26%) were alive. The median time from initial presentation until death was 41xa0days among those patients who died. The serum fibrinogen level ≥166xa0mg/dL determined at the initial visit was significantly associated with the survival time according to univariate analysis. The low histiocyte proportion in bone marrow and early initiation of treatment tended to correlate with a favorable outcome. On multivariate analysis, serum fibrinogen ≥166xa0mg/dL (hazard ratio, 0.175, Pu2009=u20090.018) was an independent clinical factor for determining the patient survival time. Despite appropriate patient management, the outcome of HS featuring HLH was grave. The serum fibrinogen level at the initial presentation was significant, and selected patients obtained some benefit from allogeneic HCT.

Prognostic implications of the immunophenotype in biphenotypic acute leukemia

The present study retrospectively analyzed clinicopathological and clinical data from 43 adult patients with biphenotypic acute leukemia (BAL) from 11 Korean institutes. The incidence of BAL was 2.1% among acute leukemias. In terms of immunophenotype, 31 patients had myeloid plus B-lymphoid (M + B), 10 had myeloid plus T-lymphoid (M + T), one had myeloid plus B-lymphoid plus T-lymphoid (M + B + T), and one had B-lymphoid plus T-lymphoid (B + T). Patients with M + T phenotype had significantly lower CR rate (55.6% vs. 88.0%, P = 0.039) and lower overall survival (0% vs. 33.9% at 5 years, P = 0.028) than those with M + B phenotype. Our results suggest that immunophenotype has prognostic implications in adult patients with BAL.

Inferior prognostic outcome in acute promyelocytic leukemia with alterations of FLT3 gene

Alterations of the FLT3 gene, in the form of internal tandem duplications (ITD) and D835 point mutations, occur frequently in acute promyelocytic leukemia (APL). We therefore evaluated the frequency and clinical relevance of FLT3 aberrations in a series of Korean APL patients. We assayed FLT3 ITD and D835 mutation status in 75 newly diagnosed APL patients and we correlated the presence of these mutations with clinical parameters and outcomes. Of the 75 patients, fifteen (20.0%) carried FLT3 mutations, nine (12.0%) with FLT3 ITD, seven (9.3%) with D835 mutations and one with both types. Patients presenting with higher leukocyte counts (>10×109/L) had a significantly higher frequency of FLT3 ITD (P = 0.030). There was no association between FLT3 aberrations and other clinicohematologic features including age, gender, M3 variant morphology and PML/RARα subtype. Death at presentation before induction chemotherapy was significantly more frequent in patients with ITD than in those without ITD (33.3% vs. 4.5%, P = 0.020), but was not significantly related to the presence of D835 mutations (28.6% vs. 5.9%, P = 0.094). Both ITD and D835 mutations were associated with shortened event-free survival (P = 0.048 and P = 0.029, respectively), but there was no correlation between disease-free survival among the 61 patients who achieved complete remission and the presence of FLT3 mutations (P = 0.543 for ITD and P = 0.277 for D835). FLT3 mutations were less frequent in Korean APL patients than in Western APL patients. In Korean patients, however, FLT3 mutations were associated with higher leukemic burdens and early deaths before remission resulting in inferior prognosis.

Significantly Better Prognosis for Patients with Primary Plasma Cell Leukemia than for Patients with Secondary Plasma Cell Leukemia

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM). Patients may either present de novo (primary PCL), or PCL may occur during the course of MM (secondary PCL). We compared the laboratory and clinical findings of both primary and secondary PCL and MM to elucidate their natural history and the relationship among these entities. Ten cases of PCL (7 cases of primary PCL and 3 cases of secondary PCL) and 20 sex- and age-matched cases of MM were compared. The patients with primary PCL showed significantly lower platelet and neutrophil counts in peripheral blood and higher cellularity in bone marrow than patients with MM (p = 0.002, < 0.001 and 0.027, respectively). Immunophenotypic studies showed a different expression of HLA-DR and CD117 antigens among the 3 groups. There was a significant difference in survival between the 3 groups (median survival of primary PCL, secondary PCL and MM = 22.2, 1.3 and 36.4 months, respectively; p = 0.048). The patients with primary PCL showed better prognosis than those with secondary PCL. Primary PCL might be a differently developed disease from MM. In diagnosing PCL, it is important to differentiate primary PCL from secondary PCL for the prediction of prognosis.

Polymerase chain reaction-based diagnosis of bone marrow involvement in 170 cases of non-Hodgkin lymphoma

Up to the current time, diagnosis of bone marrow (BM) involvement in non‐Hodgkin lymphoma (NHL) has been based on morphologic findings. Polymerase chain reaction (PCR) for antigen receptor gene rearrangements has the potential to increase the detection sensitivity of minimal degrees of BM involvement. The authors therefore assessed PCR‐based clonalities of BM concurrently with morphology from 170 cases with NHL and evaluated the usefulness of comparative analysis of clonalities between bilateral BMs and the lymph node and the clinical significance of PCR based clonalities of BM.

Myelomatous Pleural Effusion: A Case Series in a Single Institution and Literature Review

Background Myelomatous pleural effusion (MPE) is rare in myeloma patients. We present a consecutive series of patients with MPE in a single institution. Methods We retrospectively reviewed the medical records of 19 patients diagnosed with MPE between 1989 and 2008 at the Asan Medical Center. Diagnoses were confirmed by cytologic identification of malignant plasma cells in the pleural fluid. Results Our patients showed dominance of IgA (36.8%) and IgD (31.6%) subtypes. Of 734 myeloma patients, the incidence of MPE was remarkably high for the IgD myeloma subtype (16.7%), compared to the other subtypes (1.4% for IgG and 4.6% for IgA). At the time of diagnosis of MPE, elevated serum β2-microglobulin, anemia, elevated serum lactate dehydrogenase, and elevated creatinine levels were found in 100%, 89.5%, 83.3%, and 57.9% of the patients, respectively. Approximately one-third (31.3%) of the patients had adenosine deaminase (ADA) activities in their pleural fluid exceeding the upper limit of the reported cutoff values for tuberculous pleural effusion (55.8 U/L). Chromosome 13 abnormality was seen in 77.8% of the tested patients. The median survival period from the development of MPE was 2.8 months. Conclusions Patients with MPE have aggressive clinical and laboratory characteristics. The preponderance of IgD myeloma in MPE patients is a noteworthy finding because IgD myeloma is a rare subtype. Elevated ADA activity in the pleural fluid is also noteworthy, and may be helpful for detecting MPE. Physicians treating myeloma patients should monitor the development of MPE and consider the possibility of a worse clinical course.

High CXCR4 and low VLA-4 expression predicts poor survival in adults with acute lymphoblastic leukemia

Data regarding the prognostic significance of CXCR4 and VLA-4 in ALL are limited. Especially, VLA-4 has not been evaluated at the time of diagnosis in both adult and childhood ALL patients. We prospectively analyzed the expression of VLA-4 and CXCR4 in 54 patients (VLA-4 in 29 adults and 25 children and CXCR4 in 22 adults and 24 children) newly diagnosed with ALL by flow cytometry. Expression levels of VLA-4 and CXCR4 were not different between adults and children with ALL. High CXCR4 and low VLA-4 expression each correlated with worse prognosis in adults; patients with high CXCR4 expression had shorter disease-free survival (p=0.01) and overall survival (p=0.04) and patients with low VLA-4 expression had shorter disease-free survival (p=0.02). Expression levels of CXCR4 and VLA-4 did not predict patient prognosis in children. Analysis of CXCR4 and VLA-4 expression at diagnosis in adults with ALL can provide useful information on patient prognosis.