Despite extensive study, the use of allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia (AML) vary considerably. The decision of which of these options to choose is complex and depends on both clinical and molecular variables as well as the availability and histocompatability of donor stem cells. So far there is no clear explanation on whether the expression of myeloperoxidase (MPO) relates to the prognosis of AML.
Materials and Methods
We retrospectively analyzed the prognostic significance of the MPO expression in the 140 patients with diagnosed AML treated at a single institution.
In our study, MPO expression was associated with disease-free survival (DFS) and transplant was beneficial to overcome a negative prognostic effect of MPO-negative at diagnosis based upon the result that the DFS in patients received transplants are not significant between the MPO-positive group and MPO-negative group although DFS in all patients was different according to MPO expression.
MPO expression at diagnosis helps to choose therapy for each AML patient and can differentiate AML patients who need transplantation.
Myeloperoxidase; acute myeloid leukemia; prognostic factor; transplant
BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) are members of the tumor necrosis factor family and promote B cell survival and proliferation. We evaluated the correlation between serum concentration of BAFF or APRIL and severity of acute graft-versus-host disease (GVHD).
Fifteen patients who received allogeneic hematopoietic stem transplantation for leukemia and developed acute GVHD were enrolled. We determined serum concentrations of BAFF and APRIL at the onset of the first clinical manifestation of GVHD by enzyme-linked immunosorbent assay.
Nine patients had grade 2 acute GVHD, and 6 had grade 3-4 acute GVHD. The BAFF serum concentration was higher in patients with grade 3-4 acute GVHD (1,093.42 in grade 2 vs. 2,171.99 pg/mL in grade 3-4), although the difference was not significant (P=0.077). However, the ratio of BAFF serum concentration to absolute lymphocyte count (ALC) (BAFF/ALC) was significantly higher in patients with grade 3-4 acute GVHD (P=0.045). The APRIL serum concentration and APRIL/ALC ratio showed similar results (P=0.077 and P=0.013, respectively).
Patients with grade 3-4 acute GVHD had higher BAFF/ALC and APRIL/ALC ratios than patients with grade 2 acute GVHD. These findings suggest that B cells might play an important role in the development of acute GVHD, and that the BAFF and APRIL concentrations in serum might be significant predictive factors for estimating the severity of acute GVHD. Their clinical significance should be further evaluated in a larger patient population.
B cell-activating factor (BAFF); A proliferation-inducing ligand (APRIL); Acute graft-versus-host disease; Allogeneic hematopoietic stem cell transplantation
Non-small cell lung cancer (NSCLC) is the most deadly type of cancer worldwide. Although a number of therapies are used in NSCLC treatment, their therapeutic efficacy remains low. Lenalidomide was originally approved for use in patients with myelodysplastic syndromes, which are associated with 5q deletions, and multiple myeloma. Recently, lenalidomide was investigated as a new NSCLC treatment, and it exerted anticancer effects. However, the primary cellular mechanism of its effects in NSCLC is largely unknown. Therefore, we attempted to elucidate a molecular portrait of lenalidomide-mediated cellular events in NSCLC. Lenalidomide reduced the viability of several NSCLC cell lines in a concentration-dependent manner. In addition, array-based gene expression analysis revealed that lenalidomide regulated the expression of several genes associated with cell survival, apoptosis and development, including BH3-interacting domain death agonist (BID), v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) and NK2 homeobox1 (NKX2-1). BID and FOS, which are known apoptosis activators, were upregulated by lenalidomide treatment, whereas NKX2-1, which is used as an immunohistochemistry marker for NSCLC, was downregulated. These results provide evidence that lenalidomide directly induces antiproliferative effects by altering the expression of genes associated with cell proliferation and apoptosis.
lenalidomide; non-small cell lung carcinoma cell; cell growth inhibition; gene expression profiles
The overexpression of Aurora A kinase (AurA) has been reported in various malignancies, including acute myeloid leukemia (AML). However, the expression of AurA and the effects of AurA inhibition in cancer stem cells are not yet fully understood. We investigated the expression and inhibition of AurA in AML stem cells (CD34+/CD38-).
Expression of AurA was investigated in cell lines (NB4 and KG1) that express high levels of CD34 and low levels of CD38. Primary AML cells were harvested from 8 patients. The expression of AurA and cell death induced by inhibition of AurA were analyzed in CD34+/CD38- cells.
AurA was shown to be overexpressed in both primary AML cells and leukemia stem cells (LSCs) compared to normal hematopoietic stem cells. Inhibition of AurA plus cytarabine treatment in LSCs resulted in increased cytotoxicity compared to cytarabine treatment alone. Additional stimulation with granulocyte-colony stimulating factor (G-CSF) increased the cell death caused by AurA inhibition plus cytarabine treatment.
To our knowledge, this is the first report describing increased expression of AurA in LSCs. Our results suggest that selective AurA inhibition may be used to reduce LSCs, and this reduction may be enhanced by stimulation with G-CSF. Further exploration of relationship between nuclear factor kappa-B and AurA inhibition and the potential of AurA inhibition for use in leukemia treatment is needed.
Acute myeloid leukemia; Leukemia stem cell; Aurora kinase
The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.
Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.
Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001).
Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.
Primary adrenal lymphoma; Diffuse large B-cell lymphoma; Prognostic factor; R-CHOP
Anaphylactic transfusion reactions are rare complications of blood transfusions. Anhaptoglobinemia, a condition that has high incidence in Asia, can cause allergic transfusion reactions or anaphylaxis in severe cases. A 50-yr-old Korean woman was diagnosed with relapsed acute promyelocytic leukemia. She developed thrombocytopenia during chemotherapy and an anaphylactic transfusion reaction on the 4th and 5th platelet transfusions immediately after the transfusion of the platelet concentrates was initiated. Blood analysis showed no detectable serum haptoglobin. We examined her genetic phenotype and detected anhaptoglobinemia, which occurs because of an allelic deletion in the Hp gene cluster. The presence of an antibody against haptoglobin was detected by performing ELISA. To prevent anaphylactic reactions, apheresis platelets were transfused after washing. Consequently, anaphylactic transfusion reactions did not develop. Here, we report the first case of anhaptoglobinemia causing anaphylactic transfusion reaction in Korea.
Platelet transfusion; Anaphylaxis; Haptoglobin
Invasive aspergillosis (IA) is a leading cause of infectious mortality in patients who have undergone a hematopoietic stem cell transplant (HSCT); the mortality due to IA ranges from 70% to 93% in HSCT patients. Early diagnosis and treatment are the cornerstones for the good prognosis of IA. Primary renal aspergillosis is an extremely rare presentation in patients who have undergone HSCT, and the risk factor for this uncommon presentation is not well known. We report a patient who developed primary renal aspergillosis and renal stones in both the kidneys after HSCT. Invasive renal aspergillosis was diagnosed after a nephrectomy, which was performed to treat massive renal hematoma.
Primary renal aspergillosis; Hematopoietic stem cell transplant; Renal stones
The prognosis for patients with primary central nervous system (CNS) lymphoma (PCNSL) who relapse after the initial response is usually poor. A standard treatment for relapsed PCNSL has not yet been identified because of the heterogeneity of the therapies employed and the lack of large, prospective clinical trials. We describe a 46-year-old relapsed PCNSL patient who was successfully treated with intraventricular applications of rituximab to minimize neurotoxicity, 2 cycles of salvage chemotherapy with etoposide, ifosfamide, and cytarabine (VIA) regimen and high-dose chemotherapy with autologous stem cell rescue. The high-dose chemotherapy consisted of bischloroethylnitrosourea, etoposide, cytarabine, and melphalan (BEAM) regimen. Partial remission was detected after intraventricular rituximab therapy and the patient has been in complete remission without evidence of neurotoxicity for 28 months after high-dose chemotherapy with autologous stem cell rescue. This case indicates a new appropriate treatment guideline in relapsed PCNSL patient after initial intensive chemo-radiotherapy.
Primary central nervous system lymphoma; salvage therapy; rituximab; high-dose chemotherapy with autologous stem cell rescue
Laparoscopic splenectomy (LS) has been reserved for intractable and relapsing immune thrombocytopenic purpura (ITP) despite medical treatment. With further experiences of LS in ITP, we investigated long term outcomes of LS, especially newly developed morbidities, and tried to find predictive factors for favorable outcomes. From August 1994 to December 2004, fifty-nine patients whose follow-up period was more than 12 months after LS were investigated. After a long-term follow-up (median 54 months, range 12.5-129 months), a complete response (CR) was found in 28 patients (47.5%), partial response in 24 (40.7%), and no response in 7 (11.9%). The relapse rate during follow-up periods was 15.2%. The rapid response group (p=0.017), in which the platelet count increased more than twice of the preoperative platelet count within 7 days after LS, relapsing after medical treatment (p=0.02), and the satisfactory group as the initial result of LS (p=0.001) were significant for predicting CR in univariate analysis, but only the initial satisfactory group was an independent predictive factor for CR in multivariate analysis (p=0.036, relative risk=6419; 95% CI, 1.171-35.190). Infections were the most frequent morbidities during the follow-up period, which were treated well without mortality. LS is a safe and effective treatment modality for ITP. Active referral to surgery might be required, considering complications and treatment results related to long-term use of steroid-based medications.
Laparoscopic Splenectomy (LS); Immune Thrombocytopenic Purpura (ITP); Follow-up
Hepatitis B virus (HBV) reactivation is the frequent complication after cytotoxic chemotherapy in HBsAg-positive non-Hodgkin's lymphoma (NHL) patients. Pre-chemotherapy viral load may be a risk factor and HBeAg-positive status is associated with increased viral load. The aim of this study was to investigate the long-term treatment outcome of lamivudine in preventing HBV reactivation and its associated morbidity according to HBeAg status. Twenty-four adult HBsAg-positive NHL patients were taken 100 mg of lamivudine daily before the initiation of chemotherapy. The median duration of lamivudine therapy was 11.5 months (range: 1-54 months) and the median number of chemotherapy cycles was 6 (range: 1-16 cycles). The steroid containing chemotherapy regimens were used in 18 patients (75%), and the anti-CD20 monoclonal antibody containing chemotherapy regimen was used in 6 patients (25%). Four patients received autologous peripheral blood stem cell transplantation without resultant HBV reactivation. Hepatitis related to HBV reactivation was developed in 1 patient among 14 HBeAg-positive patients and no one among 10 HBeAg-negative. One patient developed HBV reactivation after lamivudine withdrawal, and 4 patients developed the YMDD (tyrosine-methionine-aspartate-aspartate) mutation during lamivudine therapy. There were no statistical differences in HBV reactivation rate during chemotherapy according to the HBeAg status. Our results demonstrate that lamivudine should be considered preemptively before the chemotherapy for all HBsAg-positive NHL patients to prevent HBV reactivation, regardless of pre-chemotherapy HBeAg status. Finally, compared with the chronic hepatitis B patients, similar rate of HBV reactivation after lamivudine withdrawal and development of YMDD mutation was observed in NHL patients.
HBV reactivation; lamivudine; non-Hodgkin's lymphoma; chemotherapy; HBeAg
Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous group of aggressive T-cell lymphomas with poor treatment outcomes. The aim of this study was to evaluate whether lymphopenia at diagnosis would have an adverse effect on survival in patients with PTCL-NOS treated with anthracycline-containing chemotherapy.
A total of 118 patients with PTCL-NOS treated with anthracycline-containing chemotherapy from 4 Korean institutions were included.
Thirty-six patients (30.5%) had a low absolute lymphocyte count (ALC, < 1.0 × 109/L) at diagnosis. Patients with lymphopenia had shorter overall survival (OS) and progression-free survival (PFS) rates compared with patients with high ALCs (P = 0.003, P = 0.012, respectively). In multivariate analysis, high-intermediate/high-risk International Prognostic Index (IPI) scores and lymphopenia were both associated with shorter OS and PFS. Treatment-related mortality was 25.0% in the low ALC group and 4.8% in the high ALC group (P = 0.003). In patients considered high-intermediate/high-risk based on IPI scores, lymphopenia was also associated with shorter OS and PFS (P = 0.002, P = 0.001, respectively).
This study suggests that lymphopenia could be an independent prognostic marker to predict unfavorable OS and PFS in patients with PTCL-NOS treated with anthracycline-containing chemotherapy and can be used to further stratify high-risk patients using IPI scores.
peripheral T-cell lymphoma; not otherwise specified; lymphopenia; international prognostic index; prognostic factor