[Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma].

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

[The expression level of secretory mature B cell surface antigen in primary diagnosed multiple myeloma and its clinical significance].

Objective: To explorer Secretory mature B cell surface antigen (sBCMA) expression level, changes during treatment and clinical significance in newly diagnosed MM patients. Methods: Clinical data of 158 MM patients admitted to the Department of Hematology, the First Affiliated Hospital of Soochow University from August 2018 to September 2020 were analyzed retrospectively. The concentration of sBCMA in the patients was determined by BCMA ELISA and compared with the normal range. The results were compared with clinical efficacy, age, type, R-ISS stage, renal impairment, and humoral immune function. Results: The median age of the patients was 57 (31-73 years old), 86 (54.5%) males and 72 (45.5%) females, mainly IgG type, 81 patients(51.2%). SBCMA value M(Q1,Q3) was 76.50 (55.50, 94.40) µg/L, 100% higher than the upper limit of normal value. According to the efficacy evaluation, the patients were divided into complete remission(CR) group, very good partial remission(VGPR) group, partial remission(PR) group and ineffiecacy group, the results showed the level of sBCMA in CR group[80.10 (58.05, 96.90) vs 15.70 (9.85, 28.65) µg/L] and VGPR group[74.60 (52.20, 93.00) vs 17.20 (13.30, 38.80) µg/L]was significantly higher than that before treatment(all P<0.001), and there was no significant difference in PR group and ineffective group before and after treatment (all P>0.05).The amount of serum intact protein M protein was positively correlated with the level of sBCMA expression in newly diagnosed patients (r=0.22, P=0.040), and there was no correlation between the proportion of bone marrow plasma cells and sBCMA expression (r=0.07, P=0.449).The correlation between sBCMA levels at initial diagnosis and MM type[IgG type, IgA type vs light chain type:(78.6±3.5), (72.4±5.4) vs (83.8±6.9)µg/L], age[≥65 vs<65 years: (73.6±5.5)vs (79.3±3.1)µg/L], R-ISS stage[stage Ⅰ, Ⅱ vs Ⅲ:(80.2±3.1) vs (69.4±6.1)µg/L], renal impairment [Creatinine clearance rate (Ccr) ≤30 vs>30 ml/min:(81.6±4.8) vs (76.5±3.4)µg/L], and high-risk karyotype[high-risk vs standard-risk:(73.6±5.7) vs (80.2±3.2)µg/L] were not associated (all P>0.05). Expression levels of sBCMA were negatively correlated with IgM levels in MM patients (r=-0.39, P=0.002) and after treatment (r=-0.25, P=0.015). Conclusions: The expression of sBCMA in MM patients is a reliable indicator of the clinical efficacy of MM and is related to the occurrence of MM immune deficiency and recovery after treatment. sBCMA can be used as a new independent marker for monitoring and predicting the efficacy of MM patients.

[A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis].

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

[Efficacy of total oral regimens containing ixazomib in patients with relapsed and refractory multiple myeloma].

To investigate the efficacy and safety of total oral regimen containing ixazomib in multidrug-resistant relapsed and refractory multiple myeloma(RRMM). A total of 38 patients were retrospectively analyzed from August 2018 to January 2020 in the First Affiliated Hospital of Soochow University. The overall response rate (ORR)was 36.8%. Among them, the very good partial response (VGPR) or better rate was 23.7%, and the complete response (CR) rate was 5.3%. The ORR was 41.7% in patients receiving ixazomib-lenalidomide-dexamethasone (IRD) regimen. Median PFS was 5 months and median OS was 7.5 months. The ORR was 50% after second-line therapy, 40% after third-line therapy and 12.5% after forth-line therapy or more. The ORR was 29.0% in bortezomib-refractory patients, 38.0% in lenalidomide-refractory patients, 21.4% in bortezmoib & lenalidomide dual refractory patients. Grade 3-4 hematological adverse events (AEs) were reported in 21% patients. Common hematological AEs included lymphopenia, neutropenia, thrombocytopenia. Other usual AEs were fatigue and diarrhea. No grade 3-4 peripheral neuropathy was recorded. In the treatment of relapsed/refractory multiple myeloma patients with multidrug resistance, the total oral regimens containing ixazomib demonstrate reliable efficacy and safety. Early administration of ixazomib at first or second relapse is suggested for more favorable clinical outcome.

[Efficacy and safety of lenalidomide combined with bortezomib and dexamethasone induction therapy in newly diagnosed patients with multiple myeloma].

Objective: This study aimed to evaluate the efficacy and safety of lenalidomide combined with bortezomib and dexamethasone (VRD) in the treatment of newly diagnosed multiple myeloma (MM) . Methods: A total of 150 newly diagnosed patients with MM diagnosed in The First Affiliated Hospital of Soochow University from November 2018 to February 2021 and received VRD as the induction regimen were included to evaluate the safety and efficacy of VRD induction therapy for newly diagnosed MM. Results: The median follow-up was 22 months, two patients (1.3%) died early after treatment, and 148 patients (98.7%) completed induction therapy. 116 patients (77.3%) were mobilized to collect autologous hematopoietic stem cells, 101 cases (87.1%) were qualified in the collection, of which 48 cases (41.4%) were excellent in the collection. The 3-year progression-free survival (PFS) rate was 59%, and the 3-year overall survival (OS) rate was 83%. After induction, complete remission (CR) /stringent CR rate was 54.4%, ≥ very good partial remission rate was 77.3%, overall response rate was 86.0%, and minimal residual disease negative rate was 46.0%. There was no statistically significant difference in the efficacy of cytogenetic high-risk patients compared with standard risk patients (P=0.456) . The median PFS time of cytogenetic high-risk patients was shorter than that of standard risk patients (not reached vs 33 months, P=0.014) . There was no statistically significant difference in the median OS time (not reached vs not reached, P=0.072) . The highest incidence of hematological adverse events was thrombocytopenia (72%) , followed by neutropenia (42%) and anemia (20%) . The highest incidence of non-hematological adverse events was peripheral neuritis (56.7%) . The main digestive tract symptoms include constipation (30.0%) and diarrhea (17.3%) . Upper respiratory tract infection (23.3%) and lung infection (7.3%) are the main infections. The incidence of adverse thrombocytopenia (90.0% vs 63.7%, P=0.001) , neutropenia (54.2% vs 36.3%, P=0.038) , anemia (33.3% vs 13.7%, P=0.005) , diarrhea (27.1% vs 12.7%, P=0.030) , limb edema (20.8% vs 3.9%, P=0.030) , fever (20.8% vs 4.9%, P=0.006) , thrombosis (8.3% vs 0, P=0.016) , and renal function deterioration (20.8% vs 3.9%, P=0.030) in patients with renal insufficiency was higher than that in patients with normal renal function. Conclusion: The VRD regimen has a significant effect on newly diagnosed MM, does not affect the hematopoietic stem cell collection, and has controllable adverse events; however, the incidence of adverse events was higher in patients with renal insufficiency.

[The efficacy and safety profile of ixazomib/lenalidomide/dexamethasone in relapsed/refractory multiple myeloma: a multicenter real-world study in China].

Objective: To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) . Methods: This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle. Results: In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion: The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

[Clinical implication of minimal residual disease monitoring by 10-color flow cytometry in multiple myeloma].

Objective: To evaluate the prognostic significance of minimal residual disease (MRD) monitoring by 10-color flow cytometry in multiple myeloma (MM) patients after treatment. Methods: 150 patients with MM who were admitted to the First Affiliated Hospital of Soochow University from July 2015 to July 2017 were retrospectively analyzed. Clinical data, MRD data monitoring by 10-color flow cytometry and prognosis were analyzed. Results: 39.1% (34/87) patients were MRD negative after induction chemotherapy, and 49.3% (34/69) patients were MRD negative within 1 year after autologous hematopoietic stem cell transplantation (ASCT) . MRD-negative patients after induction chemotherapy or after transplantation have better progress-free survival (PFS) than MRD-positive patients (P=0.022 and P<0.001) . According to the changes of MRD pre-ASCT and after ASCT, the patients were divided into 4 groups: patients with MRD continued negativity,improved from MRD positive to MRD negative, MRD continued positivity, transformed from MRD negative to MRD positive. The two-year PFS of the four groups were 83%, 82%, 44%, 0, respectively, (P=0.002) . Multivariate analysis showed that the level of MRD after induction chemotherapy was an independent factor for PFS (P=0.002) , HR=4.808 (95%CI 1.818-12.718) . Conclusion: Patients with MRD negative after treatment is a better prognosis marker than complete remission or even the best marker, which can evaluate prognosis by combining R-ISS and cytogenetic changes.

[Allogeneic CAR-T for treatment of relapsed and/or refractory multiple myeloma: four cases report and literatures review].

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.

[Outcomes of allogeneic hematopoietic stem cell transplantation in patients with paroxysmal nocturnal hemoglobinuria compared to paroxysmal nocturnal hemoglobinuria-aplastic anemia syndrome].

Objective: To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome. Methods: The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen. Results: There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×10(8)/kg in the PNH group and 10.81 (3.96-33.40) ×10(8)/kg in the PNH-AA group (P=0.668) . The median doses of CD34(+) cells infused were 5.00 (3.14-8.42) ×10(6)/kg and 3.57 (1.97-6.17) ×10(6)/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) . Conclusions: allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.

[Comparison of haploidentical hematopoietic stem cell transplantation and matched-sibling donor transplantation for the treatment of paroxysmal nocturnal hemoglobinuria].

Objective: To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) . Methods: The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups. Results: There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34+ cells infused were 10.74 (4.80-22.86) ×108/kg and 12.19 (5.14-17.25) ×108/kg (P=0.866) , 3.57 (0.68-7.80) ×106/kg and 4.00 (3.02-8.42) ×106/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups. Conclusion: The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.

[Comparison of efficacy of first-line administration of generic dasatinib or imatinib in patients with Philadelphia chromosome positive acute lymphoblastic leukemia treated by hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+) ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph(+) ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph(+) ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ(2)=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ(2)=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ(2)=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ(2)=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions: First-line administration of generic dasatinib could improve EFS for Ph(+)ALL patients treated by HSCT when compered with imatinib.

[Outcome of combination of HLA-haploidentical hematopoietic SCT with an unrelated cord blood unit for 127 patients with acquired severe aplastic anemia].

Objective: To evaluate the outcome of combination of haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) with an unrelated cord blood unit for severe aplastic anemia (SAA). Methods: The clinical data of 127 SAA patients [including 74 male and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age as 23.5(3-54) years] received HID-HSCT from September 2011 to April 2017 were analyzed retrospectively. The median interval from SAA diagnosis to transplantation was 2 (0.5-180) months. The conditioning was modified Bu/Cy+ATG/ALG-based (Busulfan + cyclophosphamide + antithymocyte immunoglobulin/antilymphocyte immunoglobulin) regimen. Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. Prophylaxis for graft-versus host disease (GVHD) was by cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX). Results: The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×10(8)/kg in the haploidentical grafts and 2.22 (1.10-7.30)×10(7)/kg in the cord blood units, respectively. The median doses of CD34(+) cells infused were 3.49(1.02-8.89) ×10(6)/kg in the haploidentical grafts and 0.56 (0.16-2.27) ×10(5)/kg in the cord blood units, respectively. Of the 127 patients, 5 patients occurred early death, one patient occurred primary graft failure. All 121 surviving patients attained complete haploidentical engraftment. The median durations of myeloid engraftment were 11 (9-28) days and 15 (9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. The incidence of infection was 58.27% (74/127). During a median follow-up of 20.5 (4-60) months, the incidence of grade Ⅱ-Ⅳ acute GVHD was 24.79% (30/121), moderate-severe chronic GVHD was 14.15% (15/106), 4-year estimated overall survival was (78.5±4.3) %, 4-year estimated failure-free survival was (77.4±4.3) %, respectively. Conclusion: Combination of HID-HSCT and an unrelated umbilical cord blood unit was a feasible choice with favorable outcome for SAA patients without matched donors.

Guidance on the management of familial hypercholesterolaemia in Hong Kong: an expert panel consensus viewpoin.

In 2016, meetings of groups of physicians and paediatricians with a special interest in lipid disorders and familial hypercholesterolaemia were held to discuss several domains of management of familial hypercholesterolaemia in adults and children in Hong Kong. After reviewing the evidence and guidelines for the diagnosis, screening, and management of familial hypercholesterolaemia, consensus was reached on the following aspects: clinical features, diagnostic criteria, screening in adults, screening in children, management in relation to target plasma low-density lipoprotein cholesterol levels, detection of atherosclerosis, lifestyle and behaviour modification, and pharmacotherapy.