Blast Percentage of Bone Marrow Aspirate on Day 14 of Induction Chemotherapy Predicts Adult Acute Lymphoblastic Leukemia Treatment Outcomes.

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.

Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia.

We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10(-3) and MR5 for ratios <10(-5). Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P = .004) or 6.3 times (P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.

Genetic Characteristics of Polycythemia Vera and Essential Thrombocythemia in Korean Patients.

BACKGROUND: Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). METHODS: We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. RESULTS: Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). CONCLUSION: This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.

OBFC2A/RARA: a novel fusion gene in variant acute promyelocytic leukemia.

Acute promyelocytic leukemia is characterized by the rearrangement of the retinoic acid receptor α (RARA) gene and its fusion with other genes. We report a novel case of variant acute promyelocytic leukemia with the karyotype der (2)t(2;17)(q32;q21). Array comparative genomic hybridization revealed distinct chromosome breakpoints within the RARA and oligonucleotide/oligosaccharide-binding fold containing 2A (OBFC2A) genes. Sequence analysis of the OBFC2A/RARA transcript showed that exon 5 of OBFC2A was fused with exon 3 of RARA through the same breakpoint as in previously described fusions of RARA. The single-stranded DNA binding protein encoded by OBFC2A is critical for genomic stability. Retention of the OB fold domain of OBFC2A in the fusion protein suggests the possibility of homodimerization. The leukemic cells from the patient showed neutrophilic differentiation in the in vitro all-trans retinoic acid assay. Mutation or rearrangement of the OBFC2A gene has not been previously reported in congenital or acquired disorders.

Long-term follow-up of imatinib plus combination chemotherapy in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia.

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph(+) ) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P < 0.0001), and overall survival (P = 0.002). During the initial phase of treatment of patients with Ph(+) ALL, it is important to maintain imatinib dose intensity.

JAK2 V617F, MPL, and CALR Mutations in Korean Patients with Essential Thrombocythemia and Primary Myelofibrosis.

Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.

Clinical significance of the appearance of abnormal protein band in patients with multiple myeloma.

Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. The appearance of abnormal protein band (APB) in MM has been reported during follow-up. We aimed to evaluate the clinical characteristics and outcomes of patients with APB in a single center cohort. A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and December 2012. We compared clinical characteristics and survival outcome between those with and without APB. Of the 377 patients, 34 (9 %) experienced APB. They comprised 18.2 % (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3.1 % (7/229) of those not receiving ASCT. APB occurred after a median of 7.9 months (range, 2.2-95.7 months) from diagnosis. Immunoglobulin isotypes at diagnosis were as follows: IgG (n = 10), IgA (n = 8), IgD (n = 5), free κ (n = 4), and free λ (n = 7). Nine patients experienced a second APB. With a median follow-up of 54.1 months, the median overall survival (OS) has not been reached in patients with APB and was 38.3 months in patients without (P < 0.001). Multivariate analysis indicated that the development of APB was a significant favorable prognostic factor for OS (hazard ratio 0.21; 95 % confidence interval 0.08-0.52). Serum ß2-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM.

Cytogenetic classification in Korean multiple myeloma patients: prognostic significance of hyperdiploidy with 47-50 chromosomes and the number of structural abnormalities.

Chromosomal abnormalities are important prognostic factors for patients diagnosed with multiple myeloma (MM). We retrospectively reviewed the clinical and laboratory data of 525 MM patients to assess the abnormalities frequently found by conventional cytogenetic analysis and to determine their relationship to prognosis and clinical parameters. Samples from 222 (42.3%) patients had abnormal karyotypes. Hyperdiploidy-1 (>50 chromosomes), hyperdiploidy-2 (47-50 chromosomes), pseudodiploidy (46 with abnormalities), and hypodiploidy (<46 chromosomes) were found in 55, 44, 42, and 81 patients, respectively. The median overall survival (OS) was significantly shorter in patients with hyperdiploidy-2 (20.9 months), pseudodiploidy (19.9 months), and hypodiploidy (18.3 months) compared with patients with normal karyotype (66 months) and hyperdiploidy-1 (55.4 months) (P < 0.001). Among patients with chromosomal abnormalities, those with 1q amplification had a shorter median OS (17 vs. 25.1 months, P = 0.018). Patients with a chromosome 13 deletion in the pseudodiploidy group also had a shorter OS. A karyotype with more than six structural abnormalities was found to have the most significant independent prognostic value by multivariate analysis. These data show that hyperdiploidy with 47-50 chromosomes should be recategorized as an unfavorable risk group, and the number of structural abnormalities needs to be considered as an important factor for prognosis. In conclusion, our findings imply that subclassification of chromosomal abnormalities by conventional cytogenetics could be applied to the prognostic assessment of MM.

Excellent outcome of haploidentical hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia.

We evaluated the outcome of children and adolescents with acquired severe aplastic anemia (SAA) who received haploidentical hematopoietic stem cell transplantation (HHCT) with in vitro T cell-depleted peripheral blood stem cells. Twelve patients with acquired SAA received a total of 15 HHCTs with in vitro CD3-depleted grafts between July 2009 and July 2012. Among the 12 patients, 11 achieved neutrophil engraftment at a median of 10 days (range, 9 to 13 days) after HHCT. One patient failed to achieve primary engraftment, and two experienced graft rejection soon after engraftment. All three patients who experienced early graft failure received a second HHCT and achieved sustained engraftment. Thus, the final engraftment rate was 100%. Acute graft-versus-host disease was assessed in 9 patients, excluding the 3 patients with early graft failure. Three of these patients developed acute graft-versus-host disease (two ≥ grade II and one with grade III). All 12 patients survived and were transfusion-independent at a median follow-up of 14.3 months (range, 4.1 to 40.7 months). Hematopoietic stem cell transplantation from haploidentical family donors with in vitro CD3 T cell depletion is a reasonable therapeutic option for children and adolescents with acquired SAA. Our future trial with a uniform protocol will help to solve the problems associated with HHCT and provide a valuable platform for the further development of HHCT as a therapy for SAA.

Immunohistopathological features of anaplastic large-cell lymphoma according to anaplastic lymphoma kinase expression and bone marrow involvement pattern.

AIMS: The immunohistopathological features of lesions involving the bone marrow (BM) were examined in patients with anaplastic large-cell lymphoma (ALCL) to identify the most useful markers for the detection of BM involvement in ALCL. METHODS AND RESULTS: A total of 80 patients with ALCL were enrolled, of whom 15 (18.8%) showed BM involvement. Anaplastic lymphoma kinase-negative (ALK-) patients (n = 11) showed a nodular BM involvement pattern more frequently than ALK+ patients (n = 4; 72.7% versus 25.0%, P = 0.095). Patients with interstitial BM involvement were more frequently ALK+ than those with nodular BM involvement (50.0% versus 11.1%, P = 0.095). CD30 positivity was the strongest indicator of the presence of BM lesions, regardless of the BM involvement pattern. The application of CD30 in cases without morphological evidence of BM involvement detected subtle BM involvement by ALCL in 13.7% of cases, which were predominantly ALK+. CONCLUSIONS: The immunohistopathological features of BM lesions in patients with ALCL differ according to ALK status and BM involvement pattern. CD30 is the most useful marker for the identification of BM lesions in ALCL patients and should be employed in all ALCL patients without exception, especially ALK+ cases.

Immunohistochemical analysis of CD123, CD56 and CD4 for the diagnosis of minimal bone marrow involvement by blastic plasmacytoid dendritic cell neoplasm.

AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive haematological malignancy derived from plasmacytoid dendritic cell precursors. Almost all patients show cutaneous manifestations, and >60% show bone marrow (BM) involvement at initial presentation. In cases where there is BM involvement by only a small number of tumour cells, such involvement is difficult to ascertain solely on morphological examination. In such situations, immunohistochemistry (IHC) may be useful in revealing minimal BM involvement by BPDCN. METHODS AND RESULTS: We investigated six patients with BPDCN. Initial morphological diagnosis disclosed BM involvement in only one of the six patients. To confirm BM involvement, IHC for CD4, CD56 and CD123 was performed on BM biopsies or clot sections. IHC revealed minimal BM involvement (CD123, 3/3; CD56, 2/3; CD4, 2/3) in three patients with BM that appeared morphologically normal. CONCLUSIONS: Our data clearly support the utility of IHC in diagnosing minimal BM involvement by BPDCN. Accordingly, we highly recommend immunohistochemical analyses for CD123, CD56 and CD4 in BPDCN patients, particularly in cases where the initial BM study indicates normal morphology.

Subtle CD20 positivity in the bone marrow of a patient who has a mucosa-associated lymphoid tissue lymphoma should not be regarded as evidence of involvement in the bone marrow.

AIMS: Bone marrow (BM) biopsies of some mucosa-associated lymphoid tissue (MALT) lymphoma patients show scattered or small clusters of CD20+ cells without definite lesions (subtle CD20 positivity). The aim of this study was to evaluate the clinical significance of BM involvement and subtle CD20 positivity in 122 patients diagnosed with MALT lymphoma. METHODS AND RESULTS: Patients were divided into three categories: BM involvement [BM(+)], subtle CD20 positivity, and no BM involvement [BM(-)]. Eleven (9%) showed BM involvement, and 17 (14%) showed subtle CD20 positivity. BM(+) patients had significantly worse progression-free survival (PFS) than BM(-) patients [hazard ratio (HR) 6.25, P = 0.01], but there was no significant difference between subtle CD20 positivity and BM(-) patients. Patients with >30 CD3+ cells among 100 nucleated cells in the areas with increased numbers of CD3+ cells had significantly worse PFS than those with <15 CD3+ cells (HR 5.49, P = 0.02). BM(+) patients with >30 CD3+ cells had worse PFS than those with ≤30 CD3+ cells (P = 0.029), with an extent of BM(+) involvement of >10% positively correlating with >30 CD3+ cells (P = 0.015). CONCLUSIONS: Patients with BM(+) MALT lymphoma showed significantly worse PFS than those with subtle CD20 positivity and BM(-) MALT lymphoma, but the PFS of patients with subtle CD20 positivity MALT lymphoma was not significantly different from that of those with BM(-) MALT lymphoma. Increased numbers of BM T cells in MALT lymphoma patients might be suggestive of a worse prognosis.

Association of cup-like nuclei in blasts with FLT3 and NPM1 mutations in acute myeloid leukemia.

The purpose of this study was to investigate the correlation of mutations of the fms-like tyrosine kinase (FLT3) and nucleophosmin (NPM1) genes with the cup-like nuclear morphology of blasts in patients with acute myeloid leukemia (AML). We retrospectively reviewed peripheral blood (PB) and bone marrow (BM) slides of 208 patients prepared at the time of diagnosis of AML based on the results of testing for mutations of both NPM1 exon 12 and FLT3. We investigated the association between this phenotype and hematologic findings, disease markers, and mutations in NPM1 exon 12, FLT3-internal tandem duplication (ITD), and tyrosine kinase domain (TKD) genes. Cup-like nuclei were found in 44 patients (21.2 %) diagnosed with AML. This morphology was associated with high blast counts in the PB and BM; AML type, especially AML M1 (FAB classification); low CD34 expression; and mutation of FLT3-ITD, -TKD, NPM1 regardless of other mutations (p < 0.05 for all). However, FLT3-ITD or TKD mutation alone (nine cases, p = 0.228) was not associated, and NPM1 mutation alone (14 cases, p = 0.036) was weakly associated with cup-like nuclei. Mutation of both NPM1 and FLT3-ITD or TKD (17 cases, p < 0.001) was strongly correlated with the cup-like nuclear morphology. AML with cup-like nuclei is strongly associated with co-occurring mutations of both NPM1 and FLT3-ITD or TKD. Therefore, testing for both mutations is recommended for patients with the cup-like nuclear morphology.

A possible role for CD8+ and non-CD8+ cell granzyme B in early small airway wall remodelling in centrilobular emphysema.

BACKGROUND AND OBJECTIVE: CD8(+) cell infiltration and apoptosis of airway epithelial cells are increased in chronic obstructive pulmonary disease (COPD). CD8(+) T cells induce apoptosis by releasing granzymes, which can also cause extracellular matrix degradation and remodelling. Granzyme B levels and T cells expressing granzyme B are increased in bronchoalveolar lavage fluid of COPD patients, which suggests that granzyme B may contribute to the pathogenesis of COPD. This study provides quantitation of granzyme B-positive cells in relation to CD8(+) cells in the small airway walls of emphysema. METHODS: Antibodies against CD8 and granzyme B were used to identify CD8(+) and granzyme B(+) cells. Volume fraction (Vv) of CD8(+) and granzyme B(+) cells were quantitated by the point counting method in the small airways of 13 non-smoker control subjects and 46 emphysema patients (14 panlobular emphysema (PLE) and 32 centrilobular emphysema (CLE) lungs). Immunohistochemical detection of macrophage scavenger receptor was also performed in randomly selected cases. RESULTS: The Vv of CD8(+) and granzyme B(+) cells in CLE was greater than those in control and PLE (both P < 0.001) subjects. The Vv of granzyme B(+) cells was greater than that of CD8(+) cells (P = 0.006), and not all CD8(+) cells were positive for granzyme B in CLE subjects. Monocytes expressing both granzyme B and macrophage scavenger receptor and granulocytes expressing granzyme B were identified. CONCLUSIONS: Upregulation of granzyme B in CD8(+) and non-CD8(+) cells is an early phenomenon of small airway wall remodelling in centrilobular emphysema and suggests its possible role in the pathogenesis of COPD.

Differential clinical characteristics of acute liver failure caused by hemophagocytic lymphohistiocytosis in children.

BACKGROUND: Children with acute liver failure (ALF) caused by hemophagocytic lymphohistiocytosis (HLH) may be at risk of undergoing unnecessary liver transplantation (LT). The aim of this study was to compare the characteristics of ALF caused by HLH with those of ALF of unknown etiology in children. METHODS: The clinical features and laboratory findings for eight children with ALF caused by HLH (ALF-HLH group) and 27 children with ALF of unknown etiology (ALF-UK group) were retrospectively compared by reviewing medical records. RESULTS: The ALF-HLH group had a higher incidence of pleural effusion, C-reactive protein elevation (especially >5 mg/dL), thrombocytopenia, anemia, fever, splenomegaly, and hypoalbuminemia (<2.5 mg/dL), and a higher in-hospital mortality rate. No significant differences were found in the white blood cell count, liver enzymes, coagulation profile, or incidence of hepatomegaly. CONCLUSIONS: LT should be performed only after it is proven that ALF is not caused by HLH, if a child with ALF shows the differential clinical features of ALF caused by HLH. Further research with larger sample sizes, however, is needed.

Immunophenotypic characterization and quantification of neoplastic bone marrow plasma cells by multiparametric flow cytometry and its clinical significance in Korean myeloma patients.

Multiparametric flow cytometry (MFC) allows discrimination between normal and neoplastic plasma cells (NeoPCs) within the bone marrow plasma cell (BMPC) compartment. This study sought to characterize immunophenotypes and quantitate the proportion of NeoPCs in BMPCs to diagnose plasma cell myeoma (PCM) and evaluate the prognostic impact of this method. We analyzed the MFC data of the bone marrow aspirates of 76 patients with PCM and 33 patients with reactive plasmacytosis. MFC analysis was performed using three combinations: CD38/CD138/-/CD45; CD56/CD20/CD138/CD19; and CD27/CD28/CD138/CD117. The plasma cells of patients with reactive plasmacytosis demonstrated normal immunophenotypic patterns. Aberrant marker expression was observed in NeoPCs, with negative CD19 expression observed in 100% of cases, CD56+ in 73.7%, CD117+ in 15.2%, CD27- in 10.5%, CD20+ in 9.2%, and CD28+ in 1.3%. In PCM patients, more than 20% of NeoPCs/BMPCs were significantly associated with factors suggestive of poor clinical outcomes. Patients who were CD27- or CD56+/CD27-, demonstrated shorter overall survival than patients of other CD56/CD27 combinations. Our results support the clinical value of immunophenotyping and quantifying NeoPCs in PCM patients. This strategy could help to reveal poor prognostic categories and delineate surrogate markers for risk stratification in PCM patients.

VEGFA and VEGFR2 genetic polymorphisms and survival in patients with diffuse large B cell lymphoma.

We evaluated the impact of functional polymorphisms in the vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor 2 (VEGFR2) genes on the survival of patients with diffuse large B cell lymphoma (DLBCL). Five potentially functional polymorphisms in the VEGFA (rs699947, rs2010963 and rs3025039) and VEGFR2 (rs1870377 and rs2305948) genes were assessed in 494 DLBCL patients treated with rituximab plus CHOP chemotherapy. The associations of genotype and haplotype with overall survival (OS) and progression-free survival (PFS) were analyzed. Of the five polymorphisms, VEGFR2 rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, patients with the AA + TA genotypes had significantly better OS (P = 0.002) and PFS (P = 0.004) than those with the TT genotype. The association between significantly better OS and the AA + TA genotypes was observed separately in patients with low (0-2; P = 0.035) and high (3-5; P = 0.043) International Prognostic Index scores. Multivariate analysis showed that, relative to the AA + TA genotypes, the TT genotype was an independent prognostic factor for poor OS (HR, 1.71; 95% CI, 1.21-2.43; P = 0.002) and PFS (HR, 1.57; 1.13-2.17; P = 0.004). Other independent significant predictors of survival in patients with DLBCL were International Prognostic Index score, age > 60 years, lactate dehydrogenase concentration >normal, extranodal disease >1 and presence of B symptoms. The VEGFR2 rs1870377 polymorphism might affect survival in patients with DLBCL, suggesting that angiogenesis might be related to poor survival in these patients.

Flow cytometric quantification and immunophenotyping of leukemic stem cells in acute myeloid leukemia.

Leukemic stem cells (LSCs) are root of clonal growth in acute myeloid leukemia (AML) and responsible for the propagation of leukemic blasts (LBs). LSCs are considered as CD34 + CD38- population among LBs and often express as CD123, CD44, or CD184, which are rarely expressed on normal hematopoietic stem cells and could be the potential therapeutic targets. Using multi-color flow cytometry, we analyzed the proportions of CD34 + CD38- LSCs and expression of CD123, CD44, and CD184 on LSCs in 63 patients with AML. The median proportion of LSCs was 1.3 % (0.0-33.1 %) at the time of diagnosis. Of all patients, 74.6 % of them had CD123-positive LSCs, all patients had CD44-positive LSCs, and 85.7 % had CD184-positive LSCs, respectively. The proportions of LSCs were significantly lower in the complete remission (CR) group compared with non-CR group (P = 0.006). The lower proportions of LSCs in CR group indicated that measurement of the proportion of LSCs might be helpful to predict the prognosis of AML.

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 49 years. 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 (n = 4) or responsive status (n = 1). After the median follow-up of 180 days, 17 (74%) died and six (26%) were alive. The median time from initial presentation until death was 41 days among those patients who died. The serum fibrinogen level ≥166 mg/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 ≥166 mg/dL (hazard ratio, 0.175, P = 0.018) 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.

Bone marrow findings of 23 Korean post-transplant lymphoproliferative disorder patients: a single-center experience.

BACKGROUND: Work-up of post-transplant lymphoproliferative disorders (PTLDs) often involves bone marrow (BM) examinations. We evaluated 23 transplant patients with PTLDs to investigate incidence of BM involvement and associated morphologic changes as well as prognosis. METHODS: We retrospectively assessed BM findings of 23 transplant patients with PTLDs who had undergone BM staging at Seoul Asan Medical Center from 1994 to 2010. RESULTS: Four (17%) showed BM involvement of PTLDs, including two pathologically diagnosed with PTLD by liver and skin biopsy and two diagnosed by BM examination. PTLD subtypes in four patients were all monomorphic, with one each having plasma cell myeloma, diffuse large B cell lymphoma, monomorphic B cell lineage, and monomorphic T-cell lineage. Epstein-Barr virus (EBV) in situ hybridization showed 11 of 23 (47.8%) patients were EBV positive, including two patients with BM involvement, one each with plasma cell myeloma and monomorphic T-cell lineage. Epstein-Barr virus infection was observed in nine of 19 patients (39.1%) without BM involvement or morphologic abnormalities. Mortality rate was higher in patients with than without BM involvement (p = 0.050). CONCLUSION: High incidence of BM involvement in patients with PTLD and high mortality rates of these patients suggest BM examination study may be important in diagnosis and staging work-up of PTLD.