Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study / 中华血液学杂志

Objective@#To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF).@*Methods@#Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated.@*Results@#Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×109/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT.@*Conclusions@#RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.

A study of clinical characteristics and prognosis of primary myelofibrosis patients with thrombocytopenia in varied degrees / 中华血液学杂志

Objective@#To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees.@*Methods@#Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated.@*Results@#320 subjects (47%) presented severe thrombocytopenia (PLT<50×109/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×109/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×109/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×109/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival.@*Conclusion@#PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes / 中华血液学杂志

Objective@#To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) .@*Methods@#112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed.@*Results@#Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ2=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model.@*Conclusion@#TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

Targeted sequencing analysis of hyper-eosinophilic syndrome and chronic eosinophilic leukemia / 中华血液学杂志

Objective@#Analysis of the molecular characteristics of eosinophilia. @*Methods@#Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. @*Results@#Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. @*Conclusion@#The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.

Gene mutations from 511 myelodysplastic syndromes patients performed by targeted gene sequencing / 中华血液学杂志

Objective@#To study the characteristics of gene mutations in Chinese myelodysplastic syndromes (MDS) patients.@*Methods@#A total of 511 Chinese patients with MDS performed 112-gene targeted sequencing were retrospectively analyzed.@*Results@#Eighty-three distinct mutant genes were found in 511 patients with MDS. Amongst these, the most frequent mutations was associated with epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) , transcription factors (24%) and cell cycle/apoptosis (17%) . 439 subjects (86%) had at least one gene mutation. The mean number of mutations in refractory anemia with unilineage dysplasia (RCUD) was 1.25, refractory anemia with multilineage dysplasia (RCMD) was 1.73, refractory anemia with ring sideroblasts (RARS) was 2.79, refractory anemia with excess blasts-1 (RAEB-1) was 2.22, RAEB-2 was 2.34, MDS with isolated 5q- was 2.67, MDS, unclassified (MDS-U) was 2.00. U2AF1 mutant subjects were more likely to have isolated+8[Q<0.001, OR=4.42 (95% CI 2.23-8.68) ]and less likely to have complex karyotypes[Q=0.005, OR=0.22 (95% CI 0.04-0.72) ]. According to the number of gene mutations, all subjects were categorized into three groups, namely group with 0-1 mutation, with 2 mutations and with three or more mutations. There was a significant difference in overall survival (OS) among three groups (P=0.041) .@*Conclusion@#About 90% patients with MDS have at least one gene mutation. Genes associated with epigenetics and spliceosome are most common mutated genes in MDS. The increased numbers of gene mutations accompany with disease evolution and associate with poor prognosis.

The efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts treated with decitabine alone or CAG/HAG regimen / 中华血液学杂志

Objective@#To observe the clinical efficacy and safety of the patients of myelodysplastic syndromes-refractory anemia with excess blasts (MDS-REAB) treated with decitabine alone or based on low dose cytarabine (Ara-C) regimen CAG/HAG [aclarubrci (ACR) /homoharring-tonine (HHT) +cytarabine+granulocyte colony stimulating factor (G-CSF) ].@*Methods@#Totally 121 patients with MDS-REAB were retrospectively analyzed, including 59 patients treated with decitabine alone (20 mg·m-2·d-1 for 5 days) , the rest 62 ones treated with low-dose Ara-C-based regimen CAG/HAG. Overall response rate (ORR) , overall survival (OS) and adverse events of the two groups were analyzed and compared retrospectively.@*Results@#The ORR of decitabine alone or CAG/HAG were 66.2% and 56.4% respectively, with no statistically significant differences (χ2=1.185, P=0.276) . Initial response rate detected by the end of first cycle of CAG/HAG was higher than that of decitabine alone (94.3% vs 69.2%) , there was statistically significant difference in the overall comparison of two groups (χ2=7.612, P=0.009) . The median OS of decitabine alone was 19.5 (95% CI 10.5-28.4) months, the median OS of CAG/HAG was 20.3 (95% CI 10.7-29.9) months, with no statistically significant differences (χ2=0.004, P=0.947) . Grade 3-4 cytopenia and infection were the most prevalent adverses of two group patients. Grade 3-4 cytopenia rate of CAG/HAG was higher than that of decitabine alone (100.0% vs 64.4%, P<0.001) . The infection rate detected at third cycle of CAG/HAG was higher than that of decitabine alone (52.9% vs 15.2%, P=0.008) .@*Conclusion@#The efficacy of treating MDS-RAEB with decitabine alone or CAG/HAG was equivalent. CAG/HAG treatment came into effect faster, but decitabine alone treatment was safer.

The clinical characteristics, gene mutations and prognosis of chronic neutrophilic leukemia / 中华血液学杂志

Objective@#To investigate the clinical manifestation, cytogenetics, gene mutations and prognostic factors of chronic neutrophilic leukemia (CNL) .@*Methods@#16 CNL cases, according to WHO (2016) -definition, were reviewed retrospectively. Identifications of the CSF3R, ASXL1, SETBP1, CALR and MPL mutations were performed by direct sequencing. JAK2 V617F mutation was detected by AS-PCR.@*Results@#Of the 16 CNL patients, the median age was 64 (43-80) years with a male predominance of 75% (12/16) . The median hemoglobin was 114 (81-154) g/L, with median WBC of 41.20 (26.05-167.70) (109/L and median PLT of 238 (91-394) ×109/L.The median level of marrow fibrosis (MF) was 1 (0-3) degree. There was no other cytogenetic abnormalities except t (1;7) (p32;q11) , +21 and 14ps+ for each. All the 16 CNL patients harbored CSF3R T618I mutation. ASXL1 mutations were identified in 81% (13/16) , while SETBP1 mutations were confirmed in 63% (10/16) . The CALR K385fs*47 mutation was found. There was no mutation in JAK2 V617F or MPL in the above 16 patients. The median overall survival (OS) of patients presented with WBC≥50×109/L at diagnosis (11 months) was significantly shorter than of WBC<50×109/L (39 months, P=0.005) .@*Conclusion@#CSF3R T618I mutation was specific for CNL. The median OS of CNL patients was 24 months, and WBC≥50×109/L at diagnosis was an unfavorable prognostic factor.

The assessment of symptomatic burden among Ph/BCR- ABL negative myeloproliferative neoplasm patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the value of myeloproliferative neoplasms Symptom Assessment Form total symptom score (MPN-SAF-TSS)in assessing constitutional symptoms among Ph/BCR- ABL negative myeloproliferative neoplasm (MPN)patients.</p><p><b>METHODS</b>A cohort of 628 MPN patients were evaluated by MPN- SAF- TSS.</p><p><b>RESULTS</b>Fatigue was the most common symptom (76.0%, 76.2%vs 89.9%)and the highest average severity of all the symptoms (3.46±2.97, 3.47±2.99vs 4.74±3.04 scores)among polycythemia vera (PV), essential thrombocythemia (ET)and primary myelofibrosis (PMF)patients. Using the MPN- SAF- TSS analysis, PMF patients showed highest burden of symptoms (28.9 ± 19.1), followed by PV patients (19.2 ± 16.8), and finally ET patients (17.1 ± 15.3). Instinct differences were observed between PMF and PV patients (χ(2)=6.371,P=0.021), PMF and ET patients (χ(2)= 14.020,P<0.001). No significant difference was found between PV and ET patients (χ(2)=2.281,P=0.191).</p><p><b>CONCLUSION</b>MPN- SAF- TSS was effective in evaluating the symptomatic burden among Ph/BCRABL negative MPN patients and could be used for serial assessment in this clinical setting.</p>

Long-term outcomes of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To estimate the long-term outcomes and the prognostic factors of homoharringtonine, cytarabine, daunorubicin or idarubicin (HAD/HAI) as induction chemotherapy in de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>The CR rate, overall survival (OS) rate, relapse free survival (RFS) rate were retrospectively assayed in 143 de novo AML patients who received the HAD/HAI induction chemotherapy. The outcomes were compared among prognostic groups according to world health organization (WHO) classification, genetic prognosis and initial white blood cell (WBC) count. The role of consolidation chemotherapy consisting of middle-dosage Ara-C (MD-Ara-C) on long term survival was evaluated.</p><p><b>RESULTS</b>Of 143 patients, 112 (78.3%) achieved CR after the first course of HAD/HAI induction treatment, and early death occurred in only one case. Notably, the CR rate of patients with an initial WBC count ≥100×10(9)/L was not significantly different from those with an initial WBC count<100× 10(9)/L (70.4% vs 80.2%, P=0.266). The CR rate for the patients with favorable, intermediate and unfavorable integrated genetics risk factors was 93.7%, 71.4% and 61.3%, respectively, the difference between groups was statistically significant (P=0.001). Patients with FLT3-ITD mutation obtained similar CR rate (70.6%) to that of patients with FLT3 wild type (79.3%, P=0.528).The estimated 5-year OS rate and 5-year RFS rate for all patients was 40.0% and 37.0%, respectively, with a median follow-up of 24 (range 1-104) months. The median survival time was 30 [95%CI (12, 48)] months. 5-year OS and 5-year RFS of the 96 patients who achieved CR after first course chemotherapy without undergoing allo-HSCT in complete remission was 47.0% and 38.0%, respectively. 5-year OS was significantly higher in MD-Ara-C consolidation group than in no MD-Ara-C consolidation group among CR patients without allo-HSCT (58.0%, 19.0%, respectively, P=0.004). In patients who obtained CR after first course and received MD-Ara-C consolidation without allo-HSCT, the 5-year OS of patients with hyperleukocytosis was not significantly lower than that of patients without hyperleukocytosis (55.5%, 58.8%, respectively,P=0.419). FLT3-ITD mutation patients showed similar 5-year OS to that of wild type FLT3 patients (51.4%, 60.2%, respectively, P=0.482). And furthermore, 5-year OS of favorable, intermediate and unfavorable integrated genetics groups were 59.1%, 62.5%, 51.9%, respectively (P=0.332) in this subgroup.</p><p><b>CONCLUSION</b>HAD/HAI induction chemotherapy with sequential consolidation of MD-Ara-C could obtain satisfactory CR rate and long-term survival rate in de novo AML, especially for patients with hyperleukocytosis or FLT3-ITD mutation. It yet remains to be verified by large sample, prospective studies.</p>

Clinical and laboratory characteristics in patients of myelodysplastic syndrome with PNH clones / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical, laboratory characteristics and PIG-A gene mutations in patients of myelodysplastic syndromes (MDS) with PNH clones.</p><p><b>METHODS</b>218 MDS patients diagnosed from August 2013 to August 2015 were analyzed. The PIG-A gene mutations were tested in 13 cases of MDS with PNH clones, 17 cases of AA-PNH and 14 cases of PNH selected contemporaneously by PCR and direct sequencing.</p><p><b>RESULTS</b>13 (5.96%) MDS patients were detected with PNH clones (13/218 cases). 9 patients were treated with cyclosporin A (CsA). Patients showed hematological improvement (HI). There were significant differences between MDS-PNH and PNH patients in terms of granulocyte clone size, red cell clone size and LDH levels [19.2% (1.0%-97.7%) vs 60.2% (3.1%-98.0%), P=0.007; 4.3% (0-67.2%) vs 27.9% (2.5%-83.6%), P=0.026; 246 (89-2014) U/L vs 1137 (195-2239) U/L, P=0.049], while the differences were not statistically significant in patients between MDS-PNH and AA-PNH patients [19.2% (1.0%-97.7%) vs 23.2% (1.5%-96.0%), P=0.843; 4.3% (0-67.2%) vs 14.4% (1.1%-62.8%), P=0.079; 246 (89-2014) U/L vs 406 (192-1148) U/L, P=0.107]. PIG-A gene mutations were detected in 7 MDS-PNH patients, of them, six were missense mutations, one were frameshift mutation and four cases with the same mutation of c.356G>A (R119Q). The PIG-A gene mutations were also detected in 9/11 AA-PNH patients and 11/14 PNH patients, both of them had the mutation of c.356G>A (R119Q). The PIG-A gene mutations of MDS-PNH, AA-PNH, PNH patients were all small mutations, the majority of those (59%) were missense mutation and mainly located in exon 2.</p><p><b>CONCLUSION</b>MDS patients with PNH clones had better response to CsA, smaller PNH clone size. The PIG-A gene mutations of MDS-PNH patients mainly located in exon 2, which could be a mutational hotspot of these patients.</p>

Prognostic evaluation of comorbidities in patients with myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To discuss the impact of comorbidities on the outcomes of patients with MDS.</p><p><b>METHODS</b>The clinical characteristics of 676 MDS patients with detailed comorbidities evaluations was analyzed retrospectively.</p><p><b>RESULTS</b>There were 395/676 cases (58.4%) with comorbidities (group 1), 281/676 cases (41.6%) without (group 2). Significant differences were seen in the distribution of age (≥ 60 y), bone marrow blasts, abnormal karyotype, WHO 2008 subtypes and IPSS-R risk cohorts (P<0.05) between the two groups. While gender, HGB concentrations, WBC levels, platelet levels and serum ferritin were not significantly different (P>0.05). Independent prognostic significance of comorbidities was seen in both uni-variate and multi-variate analyses (P<0.001). According to MDS-specific comorbidity index (MDS-CI), the median survival were 32(1-153) months, 19(2-85) months and 13(1-37) months in the low-risk, intermediate-risk and high-risk cohorts respectively, while 96(1-166) months in cohorts without any comorbidities, of which significant differences were seen (P<0.001). The MDS-CI allowed further stratification in the IPSS-R low-risk, intermediate-risk and high-risk cohorts (P<0.001).</p><p><b>CONCLUSION</b>Comorbidities provides prognostic stratification independently of IPSS-R for MDS patients.</p>

Long- term outcome of thalidomide and cyclosporine in patients with IPSS low/intermediate- 1 myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the long- term outcome of cyclosporin A (CsA) combined with thalidomide regime for Chinese patients with IPSS low/intermediate- 1 myelodysplastic syndromes (MDS) without del（5q）and the predictive variables which could impact the response to the therapy.</p><p><b>METHODS</b>Seventy-six MDS patients who were treated with these drugs at a single institute in China were retrospectively analyzed. The polymorphism of cereblon gene, rs1672753, was detected in patients of this cohort by PCR and direct sequencing.</p><p><b>RESULTS</b>A total of 53% of patients showed hematological improvement（HI）to the therapy. Thirty-one patients（31/73, 43%）achieved erythrocyte response（HI-E）; 15 patients（15/50, 30%）achieved neutrophil response（HI-N); 18 patients（18/58, 31%）achieved platelet response（HI-P). Twenty-seven of the 50 patients（46%）who were dependent on red blood cell transfusion achieved HI- E and became independent of transfusion. The median duration of response among the responders was 22 months (range, 1- 131 + months). Bone marrow blasts ≤2% was the only factor associated with longer response duration in univariate analysis （P=0.010）. There was no significant difference between the two groups of celeblon gene rs1672753 polymorphism either on the response rate or the response duration. The median survival of 67 patients without stem cell transplantation was 82 months. In multivariate analyses, factors significantly correlated with survival were IPSS-R（HR=3.461, 95%CI 1.126-10.639, P=0.030), age ≥ 60 y（HR=4.120, 95%CI 1.070-15.867, P=0.040）and HI-N（HR=7.733, 95%CI 1.007-59.396, P=0.049).</p><p><b>CONCLUSION</b>CsA combined with thalidomide regime could improve the anemia symptom in low/int-1 risk MDS patients without del（5q）. The predictive value of cereblon gene polymorphism, rs1672753, could not be verified in this study.</p>

A study of prognostic value of cytogenetics in patients with primary myelofibrosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of cytogenetics in Chinese with primary myelofibrosis (PMF).</p><p><b>METHODS</b>Four hundred and thirty-nine Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the COX proportional hazards regression model were used to evaluate the prognostic scoring systems.</p><p><b>RESULTS</b>Four hundred and thirty-nine Chinese patients with PMF were analyzed with a median age of 56 years (range: 8-83), including 298 males and 141 females. The DIPSS-plus system could effectively evaluate prognosis in Chinese patients with PMF. There was significantly higher predictive power for survival for the DIPSS-plus group compared with the DIPSS group (P=0.006, -2 log-likelihood ratios of 989.5 and 1001.9 for the DIPSS-plus and DIPSS systems, respectively). Univariate analysis indicated that the patients with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only had better survival. Following two cytogenetic risk categories were constructed: favorable karyotype including subjects with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only and unfavorable karyotype included all others. The modified DIPSS-Chinese prognostic model was proposed by adopting cytogenetic categories and DIPSS- Chinese risk group. The median survival of patients classified in low risk (163 subjects), intermediate-1 risk (187 subjects), intermediate-2 risk (82 subjects) and high risk (7 subjects) were not reached, 74 (95% CI 42-106), 39 (95% CI 26-52) and 12(95% CI 1-25)months, respectively, and there was a statistically significant difference in overall survival among the four risk groups (P<0.01).</p><p><b>CONCLUSION</b>The DIPSS-plus had significantly higher predictive power than the DIPSS group in Chinese patients with PMF and the modified DIPSS-Chinese system based on the cytogenetic features of Chinese patients was proposed and worked well for prognostic indication.</p>

Clinical efficacy analysis of recombinant human erythropoietin in the treatment of lower-risk myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and impact factors in lower-risk [International prognostic scoring system (IPSS) low or intermediate-1 risk] myelodysplastic syndrome (MDS) patients treated with recombinant human erythropoietin (rhEPO) alone or in combination with recombinant human granulocyte colony- stimulating factor (rhG-CSF).</p><p><b>METHODS</b>A total of 52 consecutive lower-risk MDS patients received subcutaneous injection of rhEPO alone or in combination with rhG-CSF at least 8 weeks, the rhEPO dose would be reduced slowly to stop or kept at minimum to maintain the response when the best efficacy achieved and maintained for 4 weeks. Their clinical features, efficacy, survival and the predictors of efficacy were analyzed retrospectively.</p><p><b>RESULTS</b>The overall response rate was 51.9% (27/52) with 33.3%(9/27) achieving complete remission (CR) and 66.7%(18/27) achieving erythroid response (HI-E). In multivariate analysis, sEPO level (less than 500 U/L), BFU-E count (more than 25/10⁵ BMMNC), intermediate and high doses rhEPO±rhG-CSF therapy were independent predictors of better response. The median therapy period was 8(2-45) months and the median efficacy duration was 37(6-94) months (38 months for CR, 36 months for HI-E). Ten of the 27 responsive patients relapsed and 40% of them had disease progressions. Hemoglobin levels and karyotype affect response duration. Median overall survival was 47(6-114) months on a 37(6-114) months median follow-up. In multivariate analysis, ages (less than 60 years old), karyotype (good or intermediate) and response to rhEPO±rhG-CSF therapy may have a favorable survival impact on MDS.</p><p><b>CONCLUSION</b>rhEPO, alone or in combination with rhG-CSF, is a useful drug for the treatment of anemia in lower-risk MDS patients and has favorable impact on life expectancy.</p>

Comparison of low-dose thalidomide and prednisone combined with or without danazol for the treatment of primary myelofibrosis-associated anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical effects of low-dose thalidomide (THAL) and prednisone (PRED) with or without danazol (DANA) in patients with primary myelofibrosis (PMF) associated anemia.</p><p><b>METHODS</b>A cohort of 58 PMF patients with anemia (Hb<100 g/L) were retrospectively studied. Of them, 28 patients were treated with THAL and PRED (THAL-PRED group), and the rest with THAL, PRED and DANA (THAL-PRED-DANA group). The hematological response was assessed according to the modified criteria of the International Working Group in 2006, and the myelofibrosis degree was evaluated at 3 and 12 month after treatment.</p><p><b>RESULTS</b>The total response rate was 56.9%(33/58) including 1.7% (1/58) partial remission (PR) and 55.2% (32/58) clinical improvement (CI). There was no statistical difference in the response rate between THAL-PRED and THAL-PREDDANA groups (50.0% vs 63.3%, P=0.306). However, the median response duration of clinical improvement, erythroid response (CI-E) and total response prolonged in THAL-PRED-DANA than THALPRED group (61.5w vs 22w, P=0.015; 75w vs 30w, P=0.007, respectively). Myelofibrosis degree at 3 and 12 months after treatment decreased significantly than before treatment (P=0.000 and 0.005, respectively). Side-effects in both groups were only grade 1-2.</p><p><b>CONCLUSION</b>Low-dose THAL together with PRED appeared to be effective in the treatment of PMF-associated anemia, and the response duration would prolong significantly if combined with DANA.</p>

Acute T-B cell biphenotypic leukemia:report of four cases with literature review / 白血病·淋巴瘤

Objective To strengh the awareness of acute T-B cell biphenotypic leukemia.Methods Four new cases of acute T-B cell biphenotypic leukemia were reported and the related literature were reviewed.Results Fourteen patients with acute T-B cell biphenotypic leukemia.including 4 diagnosed at our hospital and other 10 cases reported in literature,were retrospectively analyzed.Similar clinical fleatures as the typical acute lymphocytic leukemia(ALL) were presented.Ten of 14 cases were male and were within 17 to 46 years old.The disease were refactory to the conventional ALL chemotherapy regimens and deteriorated progressively.Six patients died within 12 months after their diagnosed with the median survival time of ten months. Conclusion Acute T-B cell biphenotypic leukemia is one of the most rare type of leukemia.A better understanding of the clinical and hematological features of this type of leukemia and new therapeutic strategies are needed.