Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report.

BACKGROUND: Multiple myeloma remains incurable despite treatment advancements over the last 20 years. LCAR-B38M Cells in Treating Relapsed/Refractory Multiple Myeloma was a phase 1, first-in-human, investigator-initiated study in relapsed/refractory multiple myeloma conducted at four sites in China. The study used LCAR-B38M chimeric antigen receptor-T cells expressing two B-cell maturation antigen-targeting single-domain antibodies designed to confer avidity, and a CD3ζ signaling domain with a 4-1BB costimulatory domain to optimize T-cell activation and proliferation. This chimeric antigen receptor construct is identical to ciltacabtagene autoleucel. In the LEGEND-2 study (n = 57, Xi'an site), overall response rate was 88%; median (95% CI) progression-free survival and overall survival were 19.9 (9.6-31.0) and 36.1 (26.4-not evaluable) months, respectively; and median follow-up was 25 months. This case study reports on a patient with relapsed/refractory multiple myeloma (λ light chain type) who was treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study (Xi'an site); he had received five prior lines of treatment and had extensive extramedullary lesions. CASE PRESENTATION: The patient, a 56-year-old Asian male, received cyclophosphamide (500 mg daily × 3 days) as lymphodepletion therapy and a total dose of 0.5 × 106 chimeric antigen receptor + T cells/kg split into three infusions (days 1, 24, and 84 from June to August 2016). He experienced grade 2 cytokine release syndrome after the first infusion; all symptoms resolved with treatment. No cytokine release syndrome occurred following the second and third infusions. His λ light chain levels decreased and normalized 20 days after the first infusion, and extramedullary lesions were healed as of January 2018. He has sustained remission for 5 years and received no other multiple myeloma treatments after LCAR-B38M chimeric antigen receptor T cell infusion. As of 30 October 2020, the patient is still progression-free and has maintained minimal residual disease-negative (10-4) complete response status for 52 months. CONCLUSIONS: This case provides support that treatment with LCAR-B38M chimeric antigen receptor T cells can result in long-term disease remission of 5 or more years without disease progression in a heavily pretreated patient with extensive extramedullary disease and no other treatment options.

Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2).

BACKGROUND: LCAR-B38M is a chimeric antigen receptor T cell product with two binding domains targeting B cell maturation antigen. Our previous reports showed a remarkable efficacy of LCAR-B38M in patients with relapsed/refractory multiple myeloma (RRMM) at a median follow-up of 2 years. Here, we report long-term safety and efficacy data from a median follow-up of 4 years. METHODS: LEGEND-2 was a phase 1, single-arm, open-label study conducted in four registered sites in China. Seventy-four participants with RRMM received LCAR-B38M treatment. Lymphodepletion was performed using cyclophosphamide or cyclophosphamide plus fludarabine. LCAR-B38M, at a median dose of 0.513 × 106 cells/kg, was intravenously administered either in three split infusions or in a single infusion. The primary objective was the safety of LCAR-B38M, and the secondary objective was efficacy. RESULTS: As of May 25, 2021, the median follow-up was 47.8 months. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were observed in 45/74 (60.8%) patients. Cytokine release syndrome (CRS) occurred in 68/74 (91.9%) cases; 7 (9.5%) had grade ≥ 3 CRS. One patient experienced grade 1 central nervous system toxicity. The overall response rate was 87.8%. Fifty-four out of 74 (73.0%) patients achieved complete response. The median progression-free survival was 18.0 months, and the median overall survival for all patients was not reached. The median duration of response was 23.3 months. Four patients experienced viral infection more than 6 months post-infusion, and four patients developed second primary non-hematological malignancies at a median time of 11.5 months post-CAR-T cell transfer. CONCLUSIONS: The 4-year follow-up data of LCAR-B38M therapy demonstrated a favorable long-term safety profile and a durable response in patients with RRMM. Trial registration Clinicaltrials.gov NCT03090659 (retrospectively registered on March 27, 2017); ChiCTR-ONH-17012285.

High Expression Levels of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 and Semaphorin 5A Indicate Poor Prognosis in Multiple Myeloma.

BACKGROUND: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. METHODS: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Affiliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. RESULTS: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical significance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). CONCLUSION: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). METHODS: This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. RESULTS: At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. CONCLUSIONS: LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.

[Screening of Serum Peptidome-Based Biomarker for Multiple Myeloma Renal Impairment].

OBJECTIVE: To screen serum peptide associated with renal impairment in patients with multiple myeloma(MM) and search early biomarker of MM renal impairment. METHODS: The weak cation exchange magnetic bead combined with matrix assisted laser desorption/ionization time of flight mass spectrometry was used to compare and analyze serum peptidome of MM with or without renal impairment. RESULTS: There were 18 peptide peaks with statistical significance in the molecular weight range from 700 to 10 000 Da(P<0.05), among them 7 peptides were upregulated and 11 were downregulated. The Quick Classifier diagnostic model composed of 3 peptides, which can strongly distinguish MM patients with or without renal impairment by means of Embedded Software. Its sensitivity and specificity were 97.14% and 94.12%, respectively. Peptides with molecular weight of 3908.85 Da and 3216.06 Da were significantly upregulated in MM patients with renal impairment, while the peptide with molecular weight of 2990.08 Da was significantly downregulated in MM patients with renal impairment. CONCLUSION: Peptides associated with MM renal impairment obtained by serum peptidome technology can provide a new clue for early assessment and diagnosis of clinical MM renal impairment.

Effect of granulocyte colony-stimulating factor priming combined with low-dose cytarabine and homoharringtonine in higher risk myelodysplastic syndrome patients.

As sensitization of leukemia cells with granulocyte colony-stimulating factor (G-CSF) can enhance the cytotoxicity of chemotherapy in myeloid malignancies, a pilot study was conducted in order to evaluate the effect of G-CSF priming combined with low-dose chemotherapy in patients with higher risk myelodysplastic syndrome (MDS). The regimen, G-HA, consisted of cytarabine (Ara-C) 7.5mg/m(2)/12h by subcutaneous injection, days 1-14, homoharringtonine (HHT) 1.5mg/m(2)/day by intravenous continuous infusion, days 1-14, and G-CSF 150mg/m(2)/day by subcutaneous injection, days 0-14. 56 patients were enrolled, 34 patients (61%, 95% confidence interval: 51.44-70.56%) achieved complete remission (CR). Median duration of neutropenia was 7days (ranging from 2 to 16days). Grade 1-2 nonhematologic toxicities were documented, including nausea and vomiting (5%), liver function abnormality (5%), and heart function abnormality (2%). No central nervous system toxicity was found. Mortality within the first 4 weeks was 4%. The G-HA regimen is effective in remission induction for higher risk MDS patients and well tolerated due to the acceptable toxicity in maintenance therapy in the patients who cannot undergo Hematopoietic cell transplantation (HCT).

[Comparison of the Effectiveness and Safety of Combined Chemotherapy with PEG-Asp for Treatment of ALL and T-NHL Patients].

OBJECTIVE: To explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients. METHODS: A total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups. RESULTS: In group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control. CONCLUSION: With higher response rate, lower drug toxicity and allergy incidence, the combined chemotherapy with PEG-Asp can replace the standard chemotherapy with L-Asp in the treatment of ALL and T-NHL. The optimization of the combined chemotheropeutic protocols for more cases and long-term survival rates need to further and deeply explorate.

[Clinical Study of Non Hodgkin's Lymphoma Treated with Enhanced Chemotherapy Regimen and Increased Treatment Courses].

OBJECTIVE: To study the non-Hodgkin's lymphoma treated with enhanced chemotherapy regimen and increase of treatment courses, including number of treatment courses, short-term efficacy, long-term survival and safety. METHODS: All the 254 cases of NHL in our hospital from January 2004 to February 2014 received a variety of intensive enhanced chemotherapy regimen, such as CHOPE, MAED, MMED and TAED. The median number of treatment course was 14, including 8 in the 1st year, 4 in the 2nd and 2 in the 3rd. RESULTS: (1) In 254 assessable patients, 182 patients (71.7%) achieved complete responses (CR), 30 patients (11.8%) achieved partial responses (PR), 22 patients (8.7%) achieved stable disease (SD), 20 patients (7.9%) achieved progressive disease (PD), 212 patients (83.5%) achieved response rate (RR). The median time of following-up was 56.5 months, the overall survivals (OS) of 1, 3 and 5 years were 90.1%, 74.5% and 61.1% respectively, the median survival time was 69 months, and the disease-free survivals (DFS) were 81.8%, 65.4% and 54.7% respectively, the median DFS was 65 months. (2) In therapeutic effects at early phase, the 3-year OS of patients who achieved CR, PR, SD and PD were 92.2%, 56.0%, 20.2% and 0% respectively; The 5-year OS of patients who achieved CR through ≤4 cycle treatments and the 5-year OS of patients who achieved CR through >4 cycles treatments were 83.1% and 6.8%, their DFS were 72.4% and 0% respectively. (3) The relapse rates of patients who received < 6, 6-8, 9-10, 11-13, 14, 15 and 20 cycle treatments were 82.5%, 78.9%, 71.9%, 65.8%, 41.8%, 30.4% and 16.7%. The response rate (RR) of patients who received 6-8 traditional chemotherapy cycle as CHOP or CHOP-like regimen were 50%-60% and relapse rate > 70%. CONCLUSION: Compared with traditional chemotherapy regimens, the dose-escalated, intensive and modified chemotherapy regimen can significatly improve the therapeutic efficiency for patients with NHL, including CR, long-term survival rate, and a good tolerance for patients. The chemotherapy intensity has been confirmed to be an important factor that associated with therapeutic efficiency. On the conditions tolerated by patients, the number of treatment cycles for NHL patients can be increased at lest 14, with 8 in the first year, 4 in the second year and 2 in the third year. The increase of chemotherapy cycle can obviously reduce the relapse rate and improve the long-term prognosis of patients. It is worth to further explore.

Busulfan plus fludarabine compared with busulfan plus cyclophosphamide as a conditioning regimen prior to hematopoietic stem cell transplantation in patients with hematologic neoplasms: a meta-analysis.

OBJECTIVES: The aim of the article is to critically appraise and synthesize available evidence regarding the efficacy and regimen-related toxicity (RRT) of Busulfan plus fludarabine (BuFlu) compared to busulfan plus cyclophosphamide (BuCy) as a conditioning regimen, prior to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with hematologic neoplasms. METHODS: A meta-analysis was attempted on clinical controlled trials (CCTs), randomized or non-randomized controlled trials (RCTs or non-RCTs), comparing BuCy with BuFlu. We did a systematic search of the indexed medical literature using appropriate keywords to identify potentially relevant articles. The primary outcome of interest was efficacy measured by overall survival (OS) and event-free survival (EFS), acute graft-versus-host-disease (aGVHD). Chronic GVHD (extensive) and other toxicity were secondary endpoints. A relative risk or risk ratio (RR) and 95% confidence interval (CI) was calculated for each outcome in the meta-analysis. RESULTS: Nine clinical controlled trials were included, of which 4 tries were RCTs involving 584 patients and the other 5 were non-RCTs involving 571 patients. The cumulative incidences of OS, EFS, acute graft-versus-host disease (aGVHD) were not significantly different between the two regimens. The non-relapse mortality was higher in BuCy but non-significant increment (RR=1.48, 95% CI: [0.97-2.26]). Liver related toxicity was significantly higher with BuCy compared to BuFlu (RR=1.90, 95% CI: [1.00-3.61]). CONCLUSION: Liver related toxicity is significantly lesser with BuFlu, but BuFlu regimen has no significant benefits compared with BuCy in OS, EFS, aGVHD. For all this, the weight of evidence favors BuFlu over BuCy as a first choice-conditioning regimen for patients with hematologic neoplasms, especially for people who have poor liver function.

[Cohort Study on GHA and New Combined Priming Chemotherapeutic Regimens in Treatment of Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome].

OBJECTIVE: To explore the clinical efficacy and adverse effects of GHA(G-CSF+homoharringtonin+cytarabine C) and new combined priming chemotherapeutic regimens(GHAA/GHTA) with high efficacy and low toxicity for treatment of relapsed and refractory acute myeloid leukemia(AML) and myelodysplastic syndrome(MDS), and to analyze the relation of above-mentioned regimens with the expression of co-stimuolating molecule B7.1. METHODS: Standard GHA regimen consisting of G-CSF: 100 µg/(m2·d) subcutaneous injection, d 0-14; homoharringtonine: 1.0 mg/(m2·d) intravenous drip, d 1-14; Ara-C: 7.5-10 mg/(m2·d) subcutaneous injection, q12h, d 1-14. Other regimens as GHAA/GHTA were combined respectively with aclarubicin 20 mg d 1-7, or pirarubicin 20 mg d 1-7. 74 patients with refractory AML and 46 patients with MDS received these priming chemotherapy. The clinical efficacy and toxicity of above-mentioned priming chemotherapy were compared with 56 patients received routine chemotherapy (MA/TAE) respectively. And the expression of costimulatory molecule B7.1 on leukemia cells in patients of different subtypes was also detected by immunofluoressence and its relationship with clinical efficiency was explored. RESULTS: (1) for AML patients treated with priming chemotherapy, the total remission was 67.56% (CR 54.05%, PR 13.51%), which was much higher than that of patients received routine chemotherapy (P<0.05). The CR rate of AML-M2 and AML-M5 group (65.51%, 61.90% respectively) was much higher than that of AML other subtypes (P<0.05), and the longest remission period lasted for 4 years; (2) for MDS patients treated with priming chemotherapy, the total remission was 60.87% (CR 45.65%, PR 15.22%), which was also significantly higher than that of patients received routine chemotherapy (P<0.05); (3) in comparison with patients received standard GHA priming regimen, the remission rate of combined priming chemotherapy GHAA/GHTA was significantly higher both in patients with AML (85.18%) and MDS (81.25%); (4) side effects after chemotheropy, including granulocyte deficiency, thrombocytopenia and anemia etc, lasted for 7-14 days; the severe infection rate was 1%, there were no severe bleeding, digest effect and damage of function in heart, liver and kidney. The therapy-related mortality was zero. Compared with routine chemotherapy, priming chemotherapy proved significantly safe and effective (P<0.05); (5) the expression rate of costimulatory molecule B7.1 showed large variance between AML and MDS, it was higher in AML-M2/AML-M5 and lower in AML of other subtypes (P<0.05). In the same case, B7.1 expression was positive correlated with efficiency of priming chemotherapy. CONCLUSION: GHA priming chemotherapy, as well as other combination regimens GHAA/GHTA, are well-tolerated, effective regimens for refractory AML and advanced MDS, without severe side effects and therapy-related mortality. Especially the new regimens GHAA/GHTA has better efficacy, which are proved more efficient than conventional GHA. Efficiency of priming chemotherapy is positive correlated with B7.1 expression, its mechanism will be further explored.

Low dose of homoharringtonine and cytarabine combined with granulocyte colony-stimulating factor priming on the outcome of relapsed or refractory acute myeloid leukemia.

BACKGROUND: To explore the effect of low dose of homoharringtonine (HHT) and cytarabine (Ara-c) combined with granulocyte colony-stimulating factor (G-CSF) priming (HAG regimen) on relapsed or refractory acute myeloid leukemia (AML). METHODS: Sixty-seven patients with relapsed or refractory acute myeloid leukemia (AML) were enrolled. All the patients were treated with HAG regimen (HHT 1.5 mg/m(2)/day, 1-14d; Ara-C 7.5 mg/m(2)/12 h, 1-14d; G-CSF 150 µg/m(2)/day, according to the counting of the peripheral white blood cells). Blood cell counting, liver, kidney function, ECG and myocardial enzymes were monitored regularly. RESULTS: Thirty-five of 67 (52.2%) patients achieved complete remission (CR) and 8/67 (11.9%) partial remission (PR). The overall response rate was 64.1%. Myelosuppression was the most frequently observed adverse effect. Sixty of 67 (89.5%) patients suffered from grade 1-4 adverse effects of hematologic toxicity (according to World Health Organization criteria) and non-hematologic toxicity was mild. CONCLUSION: In conclusion, HAG regimen was effective and tolerated well in refractory or relapsed AML. As a promising regimen for relapse or refractory AML, further observations should be made.

[Efficiency of GHA priming therapy on patients with acute monocytic leukemia and its mechanism].

The aim of this study was to explore the clinical efficiency and side effects of GHA-priming therapy on patients with acute monocytic leukemia, and to analyze its mechanism. 37 patients with refractory, relapse, hypocellular acute monocytic leukemia and elderly patients with AML-M(5) were treated with GHA-priming therapy (G-CSF, homoharringtonine and low dosage of cytarabine). Clinical efficiency, side effects, and therapy-relevant mortality were observed. By using U937 cell line as in vitro model, effect of G-CSF on cell cycle was determined by propidium iodide staining method. The inhibition rate, apoptosis rate of U937 cell line treated with various combination of G-CSF, homoharringtonine and cytarabine were detected by flow cytometry. The expression of MLAA34 on U937 before or after treating with chemotherapy was analyzed by immunohistochemical method. The results showed that in all the 37 patients, the total remission rate was 62.2% [complete remission rate was 45.95% (17/37) and partial remission rate was 16.2% (6/37)]. The incidence of granulocyte deficiency was 18.92% (2/37) with median time of 4 days. The severe infection occurred in 2 cases. No severe bleeding, no mild digestive effect occurred. Other non-hematological toxicities were low in vitro when incubated with G-CSF for 24 hours, the S-phase cells obviously increased. The inhibition rate, apoptosis rate and expression of MLAA34 of U937 cells treated by GHA significantly decreased as compared with cells treated with HA. It is concluded that the GHA priming therapy can be used to treat patients with refractory, relapse, senile and hypocellular acute monocytic leukemia with satisfied response rate and low hematological and non-hematological toxicities. G-CSF can enhance cytotoxicity of drugs such as Ara-C and HHT by promoting G(0) phase cells into the reproductive cycle. GHA and HA therapy can inhibit cell proliferation, induce apoptosis, and the former has a more significant function. GHA priming therapy can down regulate the expression of MLAA 34. MLAA-34 is a novel anti-apoptotic factor of acute monocytic leukemia.

Combination chemotherapy with low-dose cytarabine, homoharringtonine, and granulocyte colony-stimulating factor priming in patients with relapsed or refractory acute myeloid leukemia.

As sensitization of leukemic cells with granulocyte colony-stimulating factor (G-csf) can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML), a pilot study was conducted in order to evaluate the effect of G-csf priming combined with low-dose chemotherapy in patients with relapsed and refractory AML. The regimen, G-HA, consisted of cytarabine 7.5 mg/m2/12 hr by subcutaneous injection, days 1-14, homoharringtonine 1.5 mg/m2/day by intravenous continuous infusion, days 1-14, and G-csf 150 microg/m2/day by subcutaneous injection, days 0-14. Thirty-six AML patients were enrolled, 23 refractory and 13 relapsed. Eighteen patients (50%, 95% confidence interval: 33-67%) achieved complete remission (CR) with a median CR duration of 7.2 months, and two elderly patients continued a regimen of maintenance therapy and remained in remission for 26.3 and 14.1 months, respectively, as of last follow-up. Eight patients (22%) experienced neutropenia (median duration: 6 days; range: 2-22 days). Thirteen of the 36 (36%) developed severe infections. Grade 1-2 nonhematologic toxicities were documented, including nausea and vomiting (20%), liver function abnormality (6%), and heart function abnormality (6%). No central nervous system and kidney toxicity was observed. The G-HA regimen is effective in remission induction for refractory and relapsed AML patients and well tolerated in maintenance therapy in some subgroups of elderly patients. Further studies are necessary to elucidate optimum dose and schedule for this regimen to enhance the treatment efficacy of relapsed or refractory AML patients.