Distinct immunoglobulin heavy chain variable region gene repertoire and lower frequency of del(11q) in Taiwanese patients with chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in Western countries but very rare in Asia. Peripheral blood or bone marrow mononuclear cells obtained at initial diagnosis from 194 patients with CLL were analysed to determine the ethnic difference in genetic abnormalities. Mutated IGHV was detected in 71·2% of Taiwanese CLL and IGHV3-23 was the most frequently used gene. Stereotyped BCR was present in 18·3% with subset 8 being the most frequent. All cases with subset 8 belonged to IGHV 4-39 and were exclusively associated with un-mutated IGHV and poor outcome. Mutation frequencies of SF3B1 (9·7%), NOTCH1 (8·6%), BIRC3 (1·1%), ATM (16·9%) or TP53 (8·1%), and frequencies of cytogenetic abnormalities including trisomy 12 (18·6%), del(17p) (10·4%), del(13q) (43·7%) and IGH translocation (10·1%) were comparable to those reported from Western countries, except del(11q) (6·9%) which was lower in our patients. Patients with un-mutated IGHV, subset 8, disrupted TP53, trisomy 12, and SF3B1 mutations had a worse outcome compared to patients without these mutations. In conclusion, IGHV3-23 usage, stereotyped subset 8 and lower frequency of del(11q) show an ethnicity-dependent association in Taiwanese CLL patients.

Immune thrombocytopenia: Effectiveness of frontline steroids and comparison of azathioprine, splenectomy, and rituximab as second-line treatment.

OBJECTIVE: For immune thrombocytopenia (ITP), efficacy of frontline steroids is well established. However, clinical data comparing various treatment options for refractory or relapsed ITP are limited. We aimed to investigate the outcome of frontline steroid treatment for ITP patients and compare common second-line modalities in a single institute in Taiwan. METHODS: We collected the complete outpatient list over a 6-month period. Patients were identified from the list, and medical records were reviewed to capture the data retrospectively. The diagnosis of ITP was made by excluding other etiologies. RESULTS: Among 665 patients with thrombocytopenia, the diagnosis of ITP was made in 375. Two hundred and fifty-seven patients (51 males, median age 45.5) received treatment. Response to steroids was evaluable for 184 patients. Complete response (CR) was achieved in 120 (65.2%) and partial response in 43 (23.3%). In 21 (11.4%) patients, ITP was refractory to steroids. Among those with CR, 76 (63%) patients relapsed in a median of 9.5 months. After relapse or steroid failure, 57 (49%) received azathioprine treatment and 38 (32%) underwent splenectomy. Response rate was 71.4% (38.1% CR) for azathioprine and 91.4% (77.1% CR) for splenectomy. Rituximab was effective in 8 of 10 patients. CONCLUSION: Steroids are effective frontline treatment for ITP, but relapse is common. Both azathioprine and splenectomy are effective treatment after steroid failure. Rituximab appears to a reasonable second-line treatment option in our limited experience.

Extranodal NK/T-cell lymphoma, nasal type: Clinical features, outcome, and prognostic factors in 101 cases.

OBJECTIVES: We aimed to define the clinical features, outcome, and prognostic factors for extranodal NK/T-cell lymphoma (ENKTL) patients in Taiwan. METHODS: We retrospectively reviewed 101 ENKTL patients diagnosed between February 1998 and October 2015. RESULTS: The median age of 101 patients was 52 years old (range 22-85); 76.2% of patients were Ann Arbor stage I/II disease. The 5-year progression-free survival (PFS) and overall survival (OS) were 49.9% and 54.8%, respectively. Patients with log[EBV-DNA] ≥ 3.8 and bone marrow hemophagocytosis at diagnosis had inferior PFS and OS. Most stage I/II patients received combined chemoradiotherapy with anthracycline-containing regimen, with overall response rate of 96.7%, complete response rate 86.9%, 5-year PFS 65%, and OS 72%. The relapse rate was 29.3% with a short median disease-free survival of 6.2 months. In advanced stage patients, overall response rate was only 13.6%, with median PFS 2.3 months, and OS 4.8 months. Age ≥ 60 (HR 3.773, 95% CI 1.733-8.215, P = 0.001) and stage III/IV (HR 7.785, 95% CI 2.312-26.213, P = 0.001) were unfavorable prognostic factors for PFS and OS by multivariate analyses. CONCLUSIONS: Age ≥ 60 and stage III/IV are independent poor prognostic factors for PFS and OS. Early-stage ENKTL patients had good response to combined chemoradiotherapy with anthracycline-containing regimen but with a high relapse rate and short disease-free survival. Anthracycline-containing regimen in advanced stage had poor response and dismal outcome.

Clinical Features and Recurrence Pattern of Perianal Abscess in Patients with Acute Myeloid Leukemia.

INTRODUCTION: Perianal abscess may develop during neutropenia periods in patients with acute myeloid leukemia (AML). The standard of care for perianal abscess in AML is unclear. METHODS: We retrospectively collected patient data in our institute from 2009 to 2012. RESULTS: Two hundred ninety-two patients with AML were analyzed. In total, 1,051 chemotherapy sessions were administered. Twenty-three patients experienced perianal abscess. Patients with perianal abscess were younger than those without (44 vs. 60 years, p < 0.0001). Perianal abscess developed in various phases of treatment and in the stem cell transplantation period. Twelve recurrences developed in 6 patients. Patients with a prior perianal abscess have a 10-fold risk of developing a subsequent abscess following further chemotherapy. The microbiology profile revealed that most pathogens were derived from the intestinal tracts, which was similar to the findings of previous studies. The 28-day mortality was 14.3% and the direct cause of death was not perianal abscess in any case. Surgical interventions had no impact on recurrence or survival. CONCLUSION: In patients with AML, perianal abscess results from gastrointestinal tract pathogens. Many patients do not require surgical interventions. The mortality is low but recurrence is common following subsequent chemotherapies. Therefore, awareness of recurrence is important for the timely management of perianal abscess in AML.

Cyclophosphamide plus granulocyte-colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma.

We retrospectively reviewed the results of cyclophosphamide (3 g/m(2) ), doxorubicin and dexamethasone plus granulocyte-colony stimulating factor (G-CSF) (ID-CY/DOX group), low-dose cyclophosphamide (2 g/m(2) ) plus G-CSF (LD-CY group) and G-CSF alone (G-CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10(9) /L for ID-CY/DOX and LD-CY groups and after eight doses of G-CSF (5 µg/kg twice daily) for G-CSF group. For five mobilizations in ID-CY/DOX group, the rate of successful mobilization (≥4.0 × 10(6) /kg CD34+ cells) was 80%. For 78 mobilizations in LD-CY group, the successful rate was 80.8%. For 10 mobilizations in the G-CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID-CY/DOX and LD-CY groups as compared with that in G-CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID-CY/DOX and LD-CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID-CY/DOX and LD-CY plus G-CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G-CSF alone and their engraftment time were similar. Total WBC count >10 × 10(9) /L can be used as a guide to start apheresis in CY-based stem cell mobilization. J. Clin. Apheresis 31:423-428, 2016. © 2015 Wiley Periodicals, Inc.

(11)C-acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment.

PURPOSE: We investigated the potential value of (11)C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with (18)F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards. METHODS: In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48-69 years) underwent dual-tracer (11)C-ACT and (18)F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUVmax). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test. RESULTS: At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30-90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using (11)C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p=0.01). In contrast, a diagnosis of diffuse infiltration could be established using (18)F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both (11)C-ACT PET/CT and WB MRI, and in 10 patients on (18)F-FDG PET/CT. Focal lesions demonstrated (11)C-ACT uptake with a mean SUVmax of 11.4 ± 3.3 (range 4.6-19.6, n=59), which was significantly higher than the (18)F-FDG uptake (mean SUVmax 6.6 ± 3.1, range 2.3-13.7, n=29; p<0.0001). After treatment, the diffuse bone marrow (11)C-ACT uptake showed a mean SUVmax reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p=0.01). CONCLUSION: PET/CT using (11)C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using (18)F-FDG, and may be valuable for response assessment.

Phyllodes tumor in survivors of childhood osteosarcoma: a single institution's experience.

We evaluate the incidence of second neoplasms in 86 patients with osteosarcoma (OS) of the extremities treated with different protocols of adjuvant chemotherapy. Three patients developed phyllodes tumors as the second neoplasm. One of these patients simultaneously developed a third cancer with therapy-related acute myeloid leukemia. The sites of primary OS were the tibia (2) and humerus (1). None had received prior radiotherapy before excision of phyllodes tumor. All the patients were female with a median age of 21.7 years at the time of presentation. As yet, that precise causation is unclear, but it can increase our understanding of carcinogenic processes, in general.

Acute promyelocytic leukemia-associated thrombosis.

Patients with acute promyelocytic leukemia (APL) are prone to both bleeding and thrombosis. The bleeding complications are well known. In contrast, APL-associated thrombosis is relatively underappreciated. We aimed to explore the issue of APL-associated thrombosis events. In the past 20 years, 127 cases with APL were found in our hospital database. We collected their coagulation laboratory profiles, including leukemia burdens, white blood cell and platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen levels, and disseminated intravascular coagulation scores. Data were compared between patients with or without thrombosis. Clinical outcomes and potential risk factors were obtained for analysis. Ten cases with APL-associated thrombosis were found. The incidence of thrombosis was 7.9% in our cohort. Five patients had cerebral infarction, 5 had catheter-related thrombosis and 1 had acute myocardial infarction. No laboratory data were associated with clinical thrombosis. Three patients died during the induction phase but thrombosis was not the direct cause of death for any of them. We conclude that patients with APL are susceptible to thrombosis in addition to bleeding. Laboratory coagulation parameters did not predict thrombosis in our series. Ischemic stroke and catheter-related thrombosis were the most common events in our Taiwanese cohort. Such a thrombosis pattern is unique and worth further investigation.

Clinical and laboratory significance of defective P2Y(12) pathway function in patients with myeloproliferative neoplasms: a pilot study.

BACKGROUND: Patients with myeloproliferative neoplasms (MPN) have an increased risk for thrombosis and bleeding and show a defect in adenosine diphosphate (ADP)-induced platelet aggregation. This risk of thrombosis is further increased in MPN patients bearing the JAK2V617F mutation. Two ADP receptors, P2Y1 and P2Y12, are present on platelets. Although the pattern of defective ADP-induced platelet aggregation in MPN suggests an abnormality in the P2Y12 pathway, no previous studies have specifically evaluated P2Y12 function in MPN or the relationship between P2Y12 function and the JAK2V617F mutation. METHODS: Forty-one MPN patients were enrolled, including 24 with essential thrombocythemia (ET), 16 with polycythemia vera (PV) and 1 with primary myelofibrosis. Platelet P2Y12 function in MPN was evaluated by flow-cytometric measurement of the phosphorylation of vasodilator-stimulated phosphoprotein (VASP). Clinical data were collected by review of medical records. JAK2V617F mutation was detected by allele-specific polymerase chain reaction. JAK2V617F allele burden was measured by the pyrosequencing method. RESULTS: In patients with MPN, platelet P2Y12 function determined by VASP platelet reactivity index (PRI) was inversely correlated with platelet and white blood cell (WBC) counts. In subgroup analysis, PRI was inversely correlated with platelet and WBC counts in PV. PRI was also inversely correlated with platelet counts in ET, but the correlation of PRI and WBC counts did not reach statistical significance. Eight of the 41 patients had a history of thrombosis and only 2 had a bleeding history. Neither thrombosis nor bleeding patients were found to have significantly different PRIs. JAK2V617F mutation data were available in 35 cases. PRI was not different between JAK2V617F mutation and wild-type patients but PRI had a trend towards an inverse correlation with JAK2V617F allele burden for patients with mutations. CONCLUSIONS: The present study provides the first explicit demonstration of a defect in the P2Y12 pathway in platelets of patients with MPN. Furthermore, platelet P2Y12 function, assayed by VASP, is inversely correlated with platelet and WBC counts in patients with MPN. Platelet P2Y12 function also appears to be inversely correlated with JAK2V617F allele burden. This compromised P2Y12 function may be a novel mechanism for the bleeding tendency associated with extreme thrombocytosis in MPN.

The impact of age, Charlson comorbidity index, and performance status on treatment of elderly patients with diffuse large B cell lymphoma.

Treatment intensity will affect outcome in elderly patients with diffuse large B cell lymphoma (DLBCL). We retrospectively reviewed 333 DLBCL patients aged over 60 years who were diagnosed between January 2003 and December 2010 to evaluate the difference between different treatment regimens. The median age was 73 years; 56.8 % of patients received treatment with rituximab-containing regimens. In univariate analysis, patients with younger age, better performance status, early Ann Arbor stage, lower International Prognostic Index (IPI), normal serum lactate dehydrogenase, normal serum albumin, or normal serum beta-2 microglobulin received more intensive treatment regimens. In multivariate analysis, patients with younger age (p < 0.001) or better performance status (p = 0.027) received treatment of more intensive regimens. The treatment regimens were not different between patients with lower and higher Charlson comorbidity index (CCI). Female gender, normal serum beta-2 microglobulin, lower CCI, lower IPI, and treatment with more intensive regimens predicted better progression-free survival and overall survival in multivariate analysis. Patients treated with rituximab-containing regimens had better progression-free survival (median 22.2 vs. 9.9 months, p = 0.005) and better overall survival (median 34.9 vs. 21.8 months, p = 0.042) as compared to those treated without rituximab. In conclusion, our results showed that patients with younger age or better performance status received more intensive treatment. The treatment regimen was not different between patients with lower and higher CCI. Rituximab-containing regimens improved the outcome of elderly patients with DLBCL.

Value of surveillance computed tomography in the follow-up of diffuse large B-cell and follicular lymphomas.

Computed tomography (CT) as a routine follow-up has been a standard practice for patients with non-Hodgkin lymphoma although it is not recommended in most guidelines. We aimed to describe the value of surveillance CT in detection of disease relapse in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma grade 3 (FL3) and to evaluate whether relapse detected by different methods influenced outcome. In this retrospective review of consecutive 341 patients with DLBCL or FL3 diagnosed between 2003 and 2009 in complete response (CR) or unconfirmed CR, 113 patients experienced relapses. We found that routine surveillance CT detected asymptomatic relapse in 25 patients (22.1%; group 1), including 22 of 100 patients with DLBCL and three of 13 with FL3. The first presentation of relapse of the other 88 patients (group 2) included patient-reported symptoms (60.2%), physical examination (13.3%), or abnormal laboratory data (4.4%). For 72 patients received chemotherapy after relapse, the overall survival after relapse was not different between groups 1 and 2 (p = 0.569). The results of our study suggested that routine surveillance CT only has a limited role in the early detection of relapse and the relapse detected by surveillance CT or not has no impact on survival after relapse for patients with DLBCL or FL3.

Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia.

BACKGROUND: Bleeding is the leading cause of death for patients with acute promyelocytic leukemia (APL). Blood component transfusion to correct coagulopathy is the keystone in reducing bleeding. The benefit of fresh frozen plasma transfusion is unproven. Using laboratory profiles to predict bleeding is important guidance for the determination of transfusion policies in the treatment of APL. DESIGN AND METHODS: For 116 patients of APL, bleeding events were collected and correlated with various hematologic and coagulation parameters, including leukemic cell percentages, white blood cell (WBC) and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen levels, and disseminated intravascular coagulation (DIC) scores. RESULTS: Overt DIC occurred in 77.6% of patients. Severity of DIC was associated with bone marrow leukemic cell percentages but unrelated to bleeding. Patients with bleeding had significantly higher WBC counts (26.73 ± 6.18 vs. 13.03 ± 3.03 per µL, P = 0.026) and more prolonged PT (4.85 ± 0.70 vs. 2.59 ± 0.28 s, P = 0.002) and APTT (3.98 ± 1.68 vs. 0.96 ± 0.93 s, P = 0.017). Fibrinogen levels, platelet counts, and leukemia cell percentages were not significantly different between bleeding and non-bleeding patients. PT is valuable in prediction of bleeding. Patients with PT ≧ 5 s had a relative risk of 6.14 for bleeding. Seven patients had severe bleeding before initiation of all-trans retinoic acid (ATRA). CONCLUSIONS: Patients with APL are susceptible to DIC and subsequent bleeding events. Prompt ATRA administration is crucial in preventing hemorrhagic events. High WBC counts, prolonged PT, and APTT are associated with clinical bleeding in our series. PT is the most accurate parameter in predicting bleeding. Based on these findings, supportive care should be directed toward correction of coagulopathy to prevent bleeding complications and fresh frozen plasma appears to be indicated for coagulopathy associated with APL.

Complete response of myeloid sarcoma with FIP1L1-PDGFRA -associated myeloproliferative neoplasms to imatinib mesylate monotherapy.

Myeloid sarcoma (MS) is a localized, extramedullary tumor of acute myeloid leukemia (AML) that typically presents either de novo or concomitantly with myeloproliferative neoplasms (MPN), AML and myelodysplastic syndrome. Patients who have MS must be treated with intensive chemotherapy, as are patients with AML, because MS usually progresses to a systemic manifestation and leads to dismal outcomes. FIP1L1-PDGFRA-associated MPN, a subtype of myeloid and lymphoid neoplasm, is characterized by eosinophilia and abnormalities in the PDGFRA, PDGFRB or FGFR1 gene. Fusion of the FIP1L1 and PDGFRA genes activates the tyrosine kinase. As a result, imatinib mesylate (IM) is widely used for the treatment of this disorder. The coexistence of FIP1L1-PDGFRA-associated MPN and MS is extremely rare. Patients with this condition fail to achieve durable remission and long-term survival without a combination of intensive chemotherapy and IM. Here, we report a case of MS and FIP1L1-PDGFRA-associated MPN that was successfully treated with IM monotherapy.

Primary bone marrow diffuse large B cell lymphoma: a case series and review.

Diffuse large cell lymphoma involving bone marrow is not uncommon, but primary, de novo, bone marrow diffuse large B cell lymphoma (DLBCL) is rare. To understand the clinical features and outcomes of this distinct entity, we collected 12 cases in 5 years from a single-center database. They accounted for 1.16% of lymphoma, or 2.65% of diffuse large B cell lymphoma. Nine cases presented with fever of unknown origin. Lactate dehydrogenase levels were elevated in all but one case. Nine cases belonged to the high-risk group according to their international prognosis indexes (score 4 or 5). Four patients received no chemotherapy, all of whom died within 1 month. Four patients received cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP)-like chemotherapy, and their median survival was 13 months. Finally, four patients received rituximab 375 mg/m(2) in addition to CHOP-like chemotherapy. All of them had complete remission and three are still alive without relapse. We concluded that primary bone marrow DLBCL is a rare but distinctive subtype of lymphoma. The prognosis for this entity is poor but rituximab-based treatment is promising for improving its outcomes.

Primary colonic lymphoma: an analysis of 74 cases with localized large-cell lymphoma.

BACKGROUND: Surgical resection is considered a crucial treatment in patients with primary colonic lymphoma, but combining surgery with chemotherapy has provided additional therapeutic benefits in some studies. To further explore the optimal therapeutic approach in different clinical scenarios, we reviewed cases with localized large-cell lymphoma and analyzed the factors related to the outcomes. PATIENTS AND METHODS: The 74 cases diagnosed between February 1979 and October 2010 were retrospectively reviewed for clinical features, laboratory findings, and pathological diagnosis. The outcomes were correlated with their demographics and different treatment modalities. RESULTS: Of the 74 cases, only the patients who had complete tumor resection had significantly improved progression-free survival (PFS). The patients treated with resection and chemotherapy had better overall survival (OS) and PFS than those treated with resection alone. The OS and PFS of the patients who were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy without surgery were similar to those of patients treated with CHOP and resection, but the patients treated with resection followed by cyclophosphamide, vincristine, and prednisone (COP) chemotherapy had significantly better OS and PFS than the patients treated with COP chemotherapy alone. For patients with diffuse large B-cell lymphoma (DLBCL), rituximab-based chemotherapy with or without resection had similar OS and PFS. CONCLUSIONS: We conclude that chemotherapy alone provides similar therapeutic effect compared with surgery and chemotherapy and that surgical resection can be spared if an endoscopic diagnosis could be made.

Successful treatment of amegakaryocytic thrombocytopenia with azathioprine.

Acquired amegakaryocytic thrombocytopenia (AAMT) is an entity characterized by severe thrombocytopenia with a significantly reduced number of megakaryocytes in the bone marrow. AAMT is rare and poorly defined. Therefore, standard treatment is not well established. In general, steroids are considered the frontline treatment while anti-thymocyte globulin and cyclosporine are reported to be effective in scattered reports. We report a case of AAMT which was successfully treated with azathioprine 3 mg/kg/day. The clinical bleeding tendency resolved after treatment for 4 weeks and complete remission was documented after 6 weeks. Azathioprine treatment for AAMT is low risk, convenient, and cost-effective. Our successful experience suggests that azathioprine is potentially the treatment of choice after steroid failure.

Classical hairy cell leukemia and its variant: a 17-year retrospective survey in Taiwan Chinese.

BACKGROUND: Classical hairy cell leukemia (HCL-C) and its variant (HCL-V) are rare chronic B-cell lymphoproliferative disorders. Only a few reports in Chinese patients are available. METHODS: We retrospectively reviewed 16 patients with HCL-C and HCL-V in Taiwan over a 17-year period. RESULTS: Eight were HCL-C and 8 were HCL-V. All HCL accounted for 0.7% of all adult leukemias. Compared to HCL-V, HCL-C was characterized by profound leukopenia, monocytopenia, thrombocytopenia and fewer circulating hairy cells. One HCL-C and 2 HCL-V patients had second malignancies. Seven HCL-C patients achieved hematological remission after splenectomy (n = 1) or 2-chlorodeoxyadenosine (n = 6). Of the 8 HCL-V patients, 6 received splenic irradiation. Only one achieved complete remission and another had partial remission; relapse or disease progression was noted 13.4 or 25.7 months later, respectively. Two of three HCL-V patients who underwent splenectomy had stable disease. All patients with HCL-C were alive while 3 with HCL-V expired. Compared to HCL-C, HCL-V had a significantly shorter leukemia-free survival. CONCLUSION: A relatively higher proportion of HCL-V in all HCL comparing to Westerners is observed. Second malignancies are common. With an inferior outcome and dismal response to most treatment, enrollment in a clinical trial should be considered for HCL-V.

Clinical feature, image findings and outcome of hepatosplenic candidiasis in patients with acute myeloid leukemia.

BACKGROUND: Patients with acute myeloid leukemia (AML) are at risk of hepatosplenic candidiasis (HSC). HSC is often associated with prolonged fever and difficulty in definitive clinical diagnosis. We aimed to explore the incidence, clinical features, image findings and outcomes of HSC among patients with AML in a tertiary hospital, Taiwan. METHODS: We did a chart review of patient data in our institute from 2009 to 2012. The diagnosis of HSC was based on risk factors, febrile symptoms and image findings. RESULTS: Two hundred and ninety-two patients with AML were analyzed. In total, 1051 chemotherapy sessions were administered. Eleven patients (4 males and 7 females) experienced HSC (incidence 3.8%, 95% conference interval 2.11-6.72%). Among those with HSC, the median age was 62. Eight patients developed HSC following induction or re-induction chemotherapies. Three developed HSC following consolidation chemotherapies. The median duration of severe neutropenia was 25 days (range 10-142). In all patients with HSC, multiple hypodense lesions were found in the involved organs by computed tomography scans. Lesions consistent with HSC could be identified by ultrasound in 5 out of 6 patients. Other than liver and spleen, lung was frequently (7 cases) and kidney occasionally (3 cases) involved. Four patients died within 90 days. Prolonged neutropenia was associated with mortality. CONCLUSION: HSC occurred more often during induction or re-induction periods. Lungs are commonly involved and pleural effusion was frequently seen in CT scans. Pleural effusion may suggest more serious infections but its clinical relevance should be investigated in large-scale studies. Prolonged neutropenia is the only prognostic factor. Prophylaxis should be considered. In the absence of prophylaxis, we advise early image studies and prompt antifungal treatment in patients at risk for HSC.

Heterogeneous patterns of CEBPalpha mutation status in the progression of myelodysplastic syndrome and chronic myelomonocytic leukemia to acute myelogenous leukemia.

PURPOSE: We aimed to assess the role of CEBPalpha mutations in the progression of myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML) and their cooperating mutations. EXPERIMENTAL DESIGN: Mutational analysis of CEBPalpha with direct sequencing for each PCR product was done on matched bone marrow samples obtained from 50 adult patients with MDS at diagnosis and at AML transformation. Cloning analysis was used to determine the allelic distribution. RESULTS: CEBPalpha mutations were identified in four patients at diagnosis of MDS, including one with refractory anemia with excess blasts and three with chronic myelomonocytic leukemia. At AML transformation, three patients retained the identical mutant clones as their initial diagnosis, three acquired the mutations, and one lost CEBPalpha mutation when she gained FLT3/ITD mutation. Together, seven patients had CEBPalpha mutations throughout the disease course; four patients had NH(2)-terminal mutations resulting in a frameshift and truncation of the protein, three of them had two different mutations either on the same alleles or on different alleles, two had missense mutations, and one had a deletion in the basic region leucine zipper domain. Except for one with coexistence of N-ras mutation, no sample harbored cooperating mutations with FLT3 or N-ras genes. CEBPalpha mutations had no influence on the time to AML progression or overall survival. CONCLUSIONS: Our results show that CEBPalpha mutations play a role in a subset of patients with MDS, especially in chronic myelomonocytic leukemia. The mutation status was heterogeneous, exhibiting identical clone, clonal change, or clonal evolution during the progression to AML.