[Show abstract][Hide abstract] ABSTRACT: Background Hypocellular acute myeloid leukemia (Hypo-AML) is a rare disease entity. Studies investigating the biological characteristics of hypo-AML have been largely lacking. We examined the clinical and biological characteristics, as well as treatment outcomes of hypo-AML in our institutes over a seven years period. Design and Methods We retrospectively analyzed data on 631 adult AML patients diagnosed according to the French-American-British (FAB) classification and WHO classification of tumors of haematopoietic and lymphoid tissue, including 43 patients with hypo-AML. Biological variables, treatment outcomes and follow-up data on hypo-AML patients were analyzed. Results Out of 631 AML patients, 47 (7.4%) were diagnosed as hypo-AML, out of which 43 patients were evaluable. Compared with non-hypocellular AML, hypo-AML patients tended to be older (P = 0.05), more likely to present with leukocytopenia (P < 0.01) and anterior hematological diseases (P = 0.02). The overall complete remission (CR) rate, disease free survival (DFS), and overall survival (OS) in hypo-AML patients were comparable to those in non-hypo AML patients. Twenty-seven (62.8%) patients with hypocellular AML were treated with the standard regimen of anthracyclines and cytarabine (XA) (associated CR rate: 51.9%; median OS: 7 months; median DFS: 6.5 months). Sixteen (37.2%) patients were treated with a priming regimen containing homoharringtonine, cytarabine and G-CSF (HAG) (associated CR rate: 81.25%; median OS: 16 months; median DFS: 16 months). Conclusions The overall prognosis of hypo-AML was not inferior to that of non-hypo AML. HAG regimen might increase response rates and improve survival in hypo-AML patients.
[Show abstract][Hide abstract] ABSTRACT: To investigate the patients' characteristics and efficacy of prognosis evaluation by International Prognosis Scoring System (IPSS) and Revised International Prognosis Scoring System (IPSS-R) in patients with myelodysplastic syndrome (MDS).
Prognostic value of IPSS and IPSS-R was evaluated on clinical data from 159 MDS patients, according to WHO classification.
With a median age of 44 years (range:15-80 years), MDS patients had the frequency of 38.56% with abnormal karyotype, including the most common abnormality +8 (20/153, 12.6%). 34 of 142 patients transformed into leukemia. Age and the level of β2 micro-globulin were the prognostic factors by multivariate analysis and IPSS-R had a better prognostic significance. The differences in cumulative survival between IPSS subgroups were significant (P<0.05) except that between low- and intermediate I-risk group (P>0.05). There were statistical differences for IPSS-R low risk group vs high or very high risk group, and intermediate risk group vs high or very high risk group (P<0.05). IPSS-R enables IPSS subgroups re-stratification and split IPSS intermediate I-risk group into two subgroups with different prognosis.
There were significant differences in age of onset, distribution of prognosis scoring system subgroups and abnormal karyotype compared with those in Europe and America. The proportion of higher risk (worse than good karyotype) in IPSS-R was higher than that in Europe and America. Age and the level of β2 micro-globulin were prognostic factors. Both IPSS and IPSS-R were applicable in Chinese MDS patients and the latter performed better. Applying IPSS-R to re-stratify IPSS subgroups helps evaluate prognosis more accurately and improve treatment outcomes.
No preview · Article · Dec 2014 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate the clinical characteristics, treatment and prognosis of Guillain-Barre syndrome (GBS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Two cases with GBS after allo-HSCT were admitted to our hospital and a review of literatures concerning GBS developed after allo-HSCT. The clinical characteristics, treatment and prognosis were investigated.
Two patients experienced sensory disturbance and progressive muscle weakness 2 months after HSCT. The diagnosis of GBS was established after cranial MRI, lumbar puncture and EMG. Both patients died of GBS progression even after the treatment of steroid, intravenous immunoglobulin (IVIG) and plasma exchange.
GBS was a rare complication after allo-HSCT. The common clinical practices in treating GBS included IVIG and plasma exchange. Due to the primary malignant disease and low immunity posttransplant, infection, GVHD and other complications, prognosis of GBS was poor with high mortality.
No preview · Article · Aug 2014 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
[Show abstract][Hide abstract] ABSTRACT: Acute myeloid leukemia (AML) is generally regarded as a disorder of stem cells, known as leukemic initiating cells (LICs), which initiate the disease and contribute to relapses. Although the phenotype of these cells remains unclear in most patients, they are enriched within the CD34(+)CD38(-) population. In core-binding factor (CBF) AML, the cytogenetic abnormalities also exist in LIC. The aim of this study was to determine the prognostic power of minimal residual disease (MRD) measured by fluorescence in situ hybridization (FISH) in CD34(+)CD38(-) cells sorted by flow cytometry at different periods during therapy. Thirty-six patients under 65 years of age with de novo CBF-AML treated with intensive chemotherapy were retrospectively included in this study. Correlations with relapse-free survival (RFS) and overall survival were evaluated with univariate and multivariate analyses. FISH efficiently identified LICs in the CD34(+)CD38(-) population. The presence of FISH(+)CD34(+)CD38(-) cells before consolidation was negatively associated with cumulative incidence of relapse (64 vs 18 %, P = .012), which showed prognostic value for RFS (12 vs 68 %, P = .008) and OS (11 vs 75 %, P = .0005), and retained prognostic significance for RFS in multivariate analysis. The detection of FISH(+)CD34(+)CD38(-) cells before consolidation therapy significantly correlated with long-term survival. Fluorescence-activated cell sorting (FACS)-FISH could be potentially adopted as a MRD monitor approach in clinical practice to identify CBF-AML patients at risk of treatment failure during therapy.
Preview · Article · May 2014 · Annals of Hematology
[Show abstract][Hide abstract] ABSTRACT: In acute myeloid leukemia (AML), the leukemia initiating cells (LICs) or leukemia stem cells (LSCs) is found within the CD34+CD38- cell compartment. The LICs subpopulation survives chemotherapy and is most probable the cause of minimal residual disease (MRD), which in turn is thought to cause relapse. The aim of this study was to determine the prognostic value of the percentage of LICs in blasts at diagnosis.
The percentage of LICs in the blast population was determined at diagnosis using a unique Flow-FISH analysis, which applies fluorescent in situ hybridization (FISH) analysis on flow cytometry sorted cells to distinguish LICs within the CD34+CD38- cell compartment. Fourty-five AML patients with FISH-detectable cytogenetic abnormalities treated with standardized treatment program were retrospectively included in the study. Correlations with overall survival (OS), events-free survival (EFS) and cumulative incidence of relapse (CIR) were evaluated with univariate and multivariate analysis.
The percentage of LICs is highly variable in patients with acute myeloid leukemia, ranged from 0.01% to 52.8% (median, 2.1%). High LIC load (≥1%) negatively affected overall survival (2-year OS: 72.57% vs. 16.75%; P = 0.0037) and events-free survival (2-year EFS: 67.23% vs. 16.33%; P = 0.0018), which was due to an increased cumulative incidence of relapse (2-year CIR: 56.7% vs. 18.0%; P = 0.021). By multivariate analysis, high LIC load retained prognostic significance for OS and EFS.
In the present study, we established the Flow-FISH protocol as a useful method to distinguish normal and leukemic cells within the CD34+CD38- cell subpopulation. The high percentage of LICs at diagnosis was significantly correlated with increased risk of poor clinical outcome.
Preview · Article · Nov 2013 · Journal of Hematology & Oncology
[Show abstract][Hide abstract] ABSTRACT: To explore the combination therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) on acute promyelocytic leukemia (APL).
A meta-analysis of six studies was performed. Among 415 included cases, 165 cases were in the ATRA + ATO group, 129 cases in the ATRA-alone group, and 121 cases in the ATO-alone group. The complete remission (CR) rate and incidences of three groups were compared, respectively, between the therapies of ATRA + ATO with ATRA-alone, ATRA + ATO with ATO-alone, and ATRA with ATO.
The assessment results showed that ATRA + ATO therapy significantly improved the CR rate and decreased the incidences of cutaneous reaction compared with ATRA-alone (P < 0.05). However, incidence of liver injury was higher in the ATRA + ATO and ATO-alone groups than that in ATRA-alone group (P < 0.05). Difference in the complications between ATRA + ATO therapy and ATO-alone was not significant (P > 0.05).
In conclusion, we suggest low-dose ATRA and ATO combination therapy may be more effective for the treatment of APL.
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between bortezomib resistance and mutations in the proteasome beta5 subunit (PSMB5) gene.
Various bortezomib-resistant lymphoblastic lymphoma/leukemia lines were established by repeated cycles of bortezomib selection. Mutations were detected by sequencing the complementary DNA of the PSMB5 gene. Mutated clones were selected by limited dilution and cultured without bortezomib. Messenger RNA expression levels of PSMB5 in these mutated clones were measured by quantitative reverse transcription polymerase chain reaction. The degree of resistance was determined by cytotoxicity at various bortezomib concentrations. The chymotrypsin-like activities were assayed by measuring the release of the fluorescent 7-amido-4-methylcoumarin from the substrate N-succinyl-Leu-Leu-Val-Tyr-7-amido-4-methylcoumarin.
In addition to the previously reported PSMB5 G322A mutant (Ala49Thr), a C323T mutant (Ala49Val), and G322A, C326T conjoined mutant (Ala49Thr and Ala50Val) were selected and clones containing these mutations (JurkatB-G322A, JurkatB-C323T, and JurkatB-G322A/C326T) were obtained. After being cultured without bortezomib for >2 months, no significant difference in PSMB5 messenger RNA levels was detected between these JurkatB cells and parental Jurkat cells. JurkatB-G322A, JurkatB-C323T, and JurkatB-G322A/C326T clones displayed 22.0-fold, 39.4-fold, and 66.7-fold resistance, respectively, to bortezomib compared to Jurkat cells. There were no significant differences between the chymotrypsin-like activities of these mutants and Jurkat cells. The inhibitory effect of bortezomib on chymotrypsin-like activity was the weakest in JurkatB-G322A/C326T cells, and the strongest in JurkatB-G322A cells, with JurkatB-C323T cells falling in between.
Mutations of the PSMB5 gene resulting in substitutions of Ala49 and Ala50 of PSMB5 protein can confer varying bortezomib resistance.
No preview · Article · May 2009 · Experimental hematology
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to evaluate the effectiveness of bortezomib combined with epirubicin, dexamethasone, and thalidomide (BADT) for the treatment of multiple myeloma (MM). The BADT regimen consisted of a maximum of eight 4-week cycles of: intravenous bortezomib (1.0 mg/m(2)) and intravenous epirubicin (12 mg/m(2)) on days 1, 4, 8, and 11; dexamethasone (20 mg) on days 1, 2, 4, 5, 8, 9, 11, and 12; and oral thalidomide (100 mg/m(2)) on days 1-28. Twelve patients with MM were included in the study, of whom four had not been previously treated and eight had been previously treated with at least one cycle of a systemic combined regimen. All the patients completed at least two cycles of treatment, with an average of five cycles; the complete response (CR) rate was 83.3% (10/12) and stabilization of disease was 16.7% (2/12). The average number of cycles required to achieve CR was 1.9 (range 1-6). In three patients, mobilization of peripheral blood stem cells allowed a sufficient quantity of CD34+ cells to be harvested for future autotransplantation. The main adverse reactions included peripheral neuropathy (4/12), thrombocytopenia (3/12), electrocardiographic abnormalities (4/12), neutropenia (5/12), and liver function impairment (4/12), primarily grade I-II. Infection occurred in four patients with neutropenia, including one patient who developed sepsis. The estimated 1-year overall survival rate was 91.7 +/- 8.0%, and the estimated 1-year disease-free survival was 75.0 +/- 12.5%. BADT is a highly effective combined regimen, with acceptable toxicity, for the treatment of multiple myeloma.
No preview · Article · Jan 2009 · International journal of hematology
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients with non-Hodgkin’s lymphoma.
Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised: fludarabine 25∼30 mg/m2 days 1∼3, mitoxantrone 8∼10 mg/m2 day 1, and dexamethasone 20∼30 mg/m2 days 1∼5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin.
Of the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3∼4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3∼4 thrombocytopenia. At a median follow-up of 24 (5∼54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)% and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%.
FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.
No preview · Article · Nov 2008 · Chinese Journal of Clinical Oncology