Clinical Analysis Of Recombinant Human Erythropoietin In The Treatment Of Low-risk Myelodysplastic Symdromes

ObjectiveTo investigate the erythroid response and influencing factors of lower-risk myelodysplastic syndrome (MDS) patients in the treatment with recombinant human erythropoietin (rHuEPO) alone or in combination with recombinant human granulocyte colony-stimulating factor(G-CSF).MethodsTtherapeutic schedule:rHuEPO alone or in combination with G-CSF subcutaneous injection daily or every other day and the dose would reduce slowly to stop or the minimum dose to maintain respone after the maximum response had been reached.Between February2004to May2012, a total of52consecutive patients withInternational prognostic scoring system(IPSS) low or intermediate-1risk MDS received rHuEPO±G-CSF at least8weeks or more and their clinical features, efficacy, survival and the predictors of efficacy were analyzed retrospectively.ResultsIn the52patients with lower-risk MDS, there are27male and25female patients and the median of age was60years. The number of patients with various subtypes is RS4,RARS19, RCMD(RS)21, RAEB-17, and5q-syndrome1. The median hemoglobin count of patients was66.5(range29-99)g/L and the median neutrophils count was1.49(range0-10.46)×109/L, the median platelet count was96(range115-683)x109/L. Multi-lineage dysplasia of bone marrow were found in27(51.9%)patients and the percentage of45(86.5%) patients was less than5%. The median BFU-E and CFU-E counts were12/105BMMNC和57.5/105BMMNC which were both below their normal reference value (range25-37/105BMMNC and68-93/105BMMNC). Serum erythropoietin levels of43patients were less than500mU/ml. According to the IPSS karyotape prognostic group,41(76.3%) patients were with good karyotype,9(17.3%)patents with intermediate karyotype and2(3.9%) patients with poor karyotape. Here are11(21.2%) patients in low-risk group of IPSS and41(78.2%) in intermedia-risk1. The patients in each risk group of WPSS are11(21.2%) in very low-risk,16(30.8%) in low-risk,19(36.4%) in intermedian-risk and6(11.6%) in high-risk group. The median time to disease was12(range0.33-84) months and first symptoms of96.2%patients were kinds of anemia symptoms.28(53.8%) patients were dependent on transfusion.Statistical analysis showed that there were no significant difference in the general data, the condition of newly diagnosed patients, the basic level of clinical parameter, diagnostic classification and prognosis in the three groups (P>0.05) besides leukocyte and platelet.36patients received rHuEPO and16received rHuEPO+G-CSF. The effective rate of52patients in rHuEPO±G-CSF group was51.9%(27/52).9(33.3%) patients obtained complete remission (CR) and18(66.7%) patients had erythroid response (HI-E). The median efficacy duration of27patients was3(range45-74) months. There is no difference of effective rate(50%&56.3%) and efficacy duration(34&46months) between rHuEPO and rHuEPO+G-CSF group (P>0.05). Univariate(age,gender,WHO diagnosis, mul-tilineage dysplasia, percentage of bone marrow blasts,sEPO level. BFU-E and CFU-E count, karyotype, IPSS or WPSS score value and risk category, transfusion requirement,rHuEPO therapy dose. addition of G-CSF,interval from diagnosis to onset of rHuEPO±G-CSF) and multivariate (Hb level<60g/l, sEPO<500IU/ml, BFU-Ecount≥25/105BMMNC, CFU-E count, interval from diagnosis to onset of rHuEPO±G-CSF、different doses of rHuEPO)statistical analysis showed that newly diagnosed patients with sEPO<500IU/ml and BFU-E count≥25/105BMMNC, may achieve higher efficacy when accepted moderate or high dose rHuEPO therapy.Un MDS-RARS patients may remain longer efficacy duration when they accepted moderate or high dose rHuEPO therapy within5months after diagnosis confirmed. Median follow-up was36(range2-81)months,4patients had disease progressions and3of them died. The median survival time of52patients was46(range2-99)months. There was significant difference in survival time between effective and ineffective patients (52.5&29months)(P<0.05). The survival time of patients in intermedian and high dose groups were significantly longer than lower dose group30.5months (range2-72)(P<0.05). Univariate(age,gender,WHO diagnosis, multilineage dysplasia, percentage of bone marrow blasts, sEPO level. Hb level, BFU-E and CFU-E count, karyotype, IPSS or WPSS score value and risk category, transfusion requirement, the dose and therapy response of rHuEPO,addition of G-CSF,interval from diagnosis to onset of rHuEPO±G-CSF) and multivariate (the dose and therapy response of rHuEPO)statistical analysis showed that other factors had no relationship with the survival time of patients after rHuEPO therapy (P>0.05) except the dose (P=0.01)and therapy response (P=0.04)of rHuEPO.Conclusions1. There was no significant difference in the effective rate, efficacy duration and survival time between lower-risk MDS patients of rHuEPO group and rHuEPO+G-CSF group. Therefore rHuEPO therapy alone can obtain good response for lower-risk MDS patients who have anemia alone.2. Newly diagnosed lower-risk MDS patients with sEPO<500IU/ml and BFU-E count>25/105BMMNC, may achieve higher efficacy when accepted moderate or high dose rHuEPO therapy.3. Lower-risknoMDS-RARS patients may remain longer efficacy duration when they accepted moderate or high dose rHuEPO therapy within5months after diagnosis confirmed.4. Lower-risk MDS patients who received high dose therapy of rHuEPO±G-CSF and obtained good response had longer survival.