Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) .@*Methods@#The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis.@*Results@#The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK+ and 9 ones (27.3%) ALK-. Of them, 25 patients (19 ALK+ and 6 ALK-) underwent auto-HSCT and 8 cases (5 ALK+ and 3ALK-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively.@*Conclusion@#ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

The usage of comprehensive geriatric assessment in elderly patients with acute myeloid leukemia: a multicenter, prospective study / 中华血液学杂志

Objective@#To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China.@*Methods@#The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected.@*Results@#Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050).@*Conclusions@#CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients’ physical condition.

Clinical outcomes of hematopoietic stem cell transplantation for angioimmunoblastic T-cell lymphoma / 中华血液学杂志

Objective@#To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) .@*Methods@#From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively.@*Results@#Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) .@*Conclusion@#Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

Clinical outcome of allogeneic hematopoietic stem cell transplantation with FLAG sequential busulfan/cyclophosphamide conditioning regimen for refractory/relapsed acute myeloid leukemia / 中华内科杂志

Objective@#To investigate the therapeutic effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLAG sequential busulfan/cyclophosphamide(Bu/Cy) conditioning regimen for refractory/relapsed acute myeloid leukemia.@*Methods@#From February 2012 to June 2017, 21 patients with refractory/relapsed acute myeloid leukemia underwent allo-HSCT with FLAG sequential Bu/Cy conditioning regimen. Transplantation-related complications and clinical outcome were retrospectively analyzed.@*Results@#After conditioning, no hepatic veno-occlusive disease (VOD) and grade Ⅲ hemorrhagic cystitis occurred. 76.2% (16/21) patients had fever with 4 septicemia. One patient died of septic shock before engraftment. Twenty patients achieved neutrophil engraftment with a median time of 13 days (range, 10 to 21 days). Seventeen patients achieved platelet engraftment with a median time of 18 days (range, 9 to 25 days). The cumulative incidence of acute graft-versus-host disease (aGVHD) was 39.5%, and 3 patients developed grade Ⅲ-Ⅳ aGVHD. Of 19 patients who survived more than 100 days after transplantation, 4 had local chronic graft-versus-host disease (cGVHD). Of 21 patients, the median survival time was 15 months (range, 0.5 to 67 months) post-transplantation. Transplantation-related mortality rate was 28.7%. Leukemia relapse occurred in 4 patients with a median time of 4 months (range, 3 to 8 months) after transplantation. The cumulative relapse rate at 1 year was 21.4%. The 1-year and 3-year overall survival (OS) rates were 60.7% and 54.9% respectively. Log-rank analysis revealed that bone marrow blasts ≥ 20% or extramedullary leukemia before transplantation, poor platelet engraftment and grade Ⅲ-Ⅳ aGVHD were significantly related to shortened OS (P<0.05).@*Conclusions@#Allo-HSCT with FLAG sequential Bu/Cy conditioning regimen in patients with refractory/relapsed myeloid leukemia has acceptable transplantation-related risk and relapse rate. The 1-year and 3-year OS rates are comparable with those in remission patients.

Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu).</p><p><b>METHODS</b>A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively.</p><p><b>RESULTS</b>All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS.</p><p><b>CONCLUSION</b>Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.</p>

Efficacy comparison between Ph⁺ ALL patients treated with chemotherapyplus tyrosine kinase inhibitors followed by allo-HSCT and Ph-ALL patients with allo-HSCT: a case control study from a single center / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy of the Ph⁺ acute lymphoblastic leukemia (ALL)patients treated with combination of tyrosine kinase inhibitors (TKI)and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and Ph⁻ ALL patients with allo-HSCT.</p><p><b>METHODS</b>A total of 19 Ph⁺ALL patients were matched with 19 Ph⁻ALL patients from 55 B-ALL patients receiving allo-HSCT in our hospital between January 2003 and August 2014 and were analyzed retrospectively.</p><p><b>RESULTS</b>Gender, median age, number of patients with blood white count more than 30 × 10⁹/L, number of patients with meningeal leukemia, disease status before allo-HSCT, period of allo-HSCT, the source of stem cell from donors, HLA disparities between donor and recipient, conditioning regimens and number of infused mononuclear cells and CD34⁺ cells were comparable between two groups of Ph⁺ and 19 Ph⁻ALL patients. The median time of engraftment of neutrophil cells was 12 days versus 13 days (P= 0.284) and that of platelet 14 days versus 17 days (P=0.246), which were comparable between two groups. The estimated 3-year overall survival (OS) in Ph⁺ and Ph⁻ALL groups was (67.5 ± 12.4)% versus (74.3 ± 11.4)% (P=0.434) and 3-year disease free survival (DFS)was (67.8 ± 12.4)% versus (74.3 ± 11.4)% (P= 0.456), respectively. The cumulative incidence of degree Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD)in Ph⁺ and Ph⁻ ALL group was (15.8±8.4)% versus (21.1 ± 9.4)% (P=0.665)and that of degree Ⅲ-Ⅳ aGVHD was (5.6 ± 5.4)% versus (11.5 ± 7.6)% (P=0.541), respectively. The cumulative incidence of cGVHD was (44.1 ± 14.0)% in Ph⁺ALL group versus (44.1 ± 13.0)% in Ph⁻ALL group (P=0.835) and that of extensive cGVHD was (13.1 ± 8.7)% versus (6.2 ± 6.1)% (P=0.379), respectively. The cumulative relapse rate and the cumulative non-relapse rate in both group also have no statistical difference [(10.8 ± 7.2)% versus (20.0 ± 10.7)% (P=0.957) and (23.9 ± 12.4)% versus (7.1±6.9)% (P=0.224), respectively].</p><p><b>CONCLUSION</b>The efficacy of Ph⁺ALL treated with combination of chemotherapy and TKIs and followed by allo-HSCT is comparable to that of Ph⁻ALL with allo-HSCT.</p>

Clinical investigation of reduced-dose voriconazole on primary prevention in invasive fungal disease after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and tolerability of intravenous voriconazole on primary prevention in invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>At the time of conditioning regimen, patients without IFD was intravenously administered with voriconazole at a dose of 100 mg two times per day until neutrophils greater than 0.5×10⁹/L. Patients treated with oral fluconazole, 200 mg per day, were control group. The incidence and risk factors of IFD and side effects of medicines were evaluated.</p><p><b>RESULTS</b>Of the total 227 patients, 33 (14.54%) had IFD within 3 months after allo-HSCT. There was significant difference on overall survival between patients with or without IFD by Kaplan-Meier survival curve (P=0.029). Of the 83 cases with intravenous voriconazole, 7 cases occurred IFD (8.43%). In contrast, the incidence of IFD in control group was 18.06% (26 out of 144). There was remarkable difference between the two groups (P=0.048). But there was no significant difference on risk factors of IFD between the two groups. In addition, the incidence of liver function abnormalities between the two groups was no difference. The ratio of auditory hallucination and visual impairment induced by voriconazole was not high.</p><p><b>CONCLUSION</b>Intravenous voriconazole on primary prevention for IFD after allo-HSCT is much better than oral fluconazole with well tolerability and satisfactory efficacy.</p>

Long term follow-up and prognostic analysis of 85 cases with primary gastrointestinal diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics, prognostic factors in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL).</p><p><b>METHODS</b>Long term follow-up of 85 patients with PGI-DLBCL was carried out and the patients clinical data were retrospectively evaluated. The risk factors for survival rate were analyzed by univariate and multivariate Cox regression analysis.</p><p><b>RESULTS</b>The median age of 85 patients was 61 years old (18-87), and male: female ratio was 1.83:1 (55/30). The stomach origin accounted for 63.5% (54/85), intestine origin for 35.3% (30/85) and multiple GI involvements for 1.2% (1/85). Bone marrow involvement accounted for 16.4% (11/64), Helicobacter pylori (HP) infection for 51.4% (19/37). The 5-year overall survival (OS) rates of all patients were 63.9%. The 5-year OS of patients in stomach and intestinal groups were 75.3% and 44.1%, respectively (P=0.005). The 5-year OS of germinal center B cell-like (GCB) group and non-GCB groups were 64.7% and 62.4%, respectively (P = 0.610). Univariated analysis revealed that the factors affecting OS of patients included age, lesion site, tumor size, gastrointestinal clinical Lugano staging system, IPI score (all P values < 0.05). Multivariate Cox regression analysis revealed that IPI score was independent prognosis risk factor affecting OS (RR = 3.609, 95 CI 2.034-6.404, P < 0.01).</p><p><b>CONCLUSION</b>IPI score was independent prognosis risk factor affecting OS of PGI-DLBCL patients.</p>

Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences, and currently no effective therapy exists. This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage total body irradiation (TBI), and to explore the potential immunoprotective role of MSCs.</p><p><b>METHODS</b>BALB/c mice were treated with 8 Gy TBI, and then some were administered CB-MSCs isolated from C57BL/6 mice. Survival rates and body weight were analyzed for 14 days post-irradiation. At three days post-irradiation, we evaluated IFN-γ and IL-4 concentrations; CD4(+)CD25(+)Foxp3(+) regulatory T cell (Treg) percentage; CXCR3, CCR5, and CCR7 expressions on CD3(+) T cells; and splenocyte T-bet and GATA-3 mRNA levels. CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM) assay.</p><p><b>RESULTS</b>After lethal TBI, compared to non-transplanted mice, CB-MSC-transplanted mice exhibited significantly increased survival, body weight, and CFU-GM counts of bone marrow cells (P < 0.05), as well as higher Treg percentages, reduced IFN-γ, CXCR3 and CCR5 down-regulation, and CCR7 up-regulation. CB-MSC transplantation suppressed Th1 immunity. Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells, and CB-MSC co-culture reversed this inhibition.</p><p><b>CONCLUSION</b>Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity, and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition, expanding Tregs, regulating T cell chemokine receptor expressions, and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.</p>

Bortezomib-based chemotherapy for patients with multiple myeloma: a single center experience / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of bortezomib-based chemotherapy for 80 patients with multiple myeloma (MM).</p><p><b>METHODS</b>A total of 80 cases with a median age of 57 (range: 25-78) years were enrolled in the study. Bortezomib-based regimens included VD (bortezomib and dexamethasone) and PAD (bortezomib, doxorubicin and dexamethasone). 16 of the 80 patients received autologous or allo-hematopoietic stem cell transplantation (HSCT).</p><p><b>RESULTS</b>The overall response (OR) rate was 80%, including a complete response (CR) of 46.3%. After a median follow-up of 25 months, the 1-year and 2-year overall survival (OS) was 81.4% and 72.9%, and the 2-year progression-free survival (PFS) was 76% and 62.5%, respectively. The 2-year OS and PFS were 100% and 73.9 % in patients with HSCT, while both were 66% (P=0.029) and 58.7% (P=0.447) in patients without HSCT. In univariate analysis, Durie-Salmon group, ISS stage, CR and very good partial response (VGPR), and HSCT were prognostic factors for OS. Gender and extramedullary plasmacytomas were important prognostic factors for PFS. Multivariate analysis by Cox regression revealed that CR and VGPR, Durie-Salmon group A, and HSCT were prognostic factors for better OS; while male and patients without extramedullary plasmacytomas were prognostic factors for longer PFS.</p><p><b>CONCLUSION</b>MM patients could benefit from bortezomib-based chemotherapy with satisfactory efficacy and safety. HSCT could improve the OS for young MM patients.</p>

Effect of CAG induction therapy in patients with acute myeloid leukemia / 中国综合临床

Objective To assess the effect of low-dose cytarabine and aclarubicin in combination with gran-ulocyte colony-stimulating factor (G-CSF) protocol (CAG) in patients with acute myeloid leukemia (AML),and to understand the potential factors affecting the outcome of CAG induction therapy, therefore to find the optimum pa-tients for CAG therapy. Methods Twenty-one AML patients were enrolled in the current study. All patients were treated with CAG regimen including cytarabine (10 mg/m~2, subcutaneously, every 12 h, days 1 - 14), lacinomycin (5～7 mg/m~2,intravenously,every day, days 1 -8) ,and G-CSF (200 μg/m~2,subcutaneously, every day,12 h be-fore Ara-C was given) priming. Results The overall complete remission (CR) rate of the 21 AML patients was 66.7% (14/21). The CR rates was 87.5% (7/8) in patients older than 60 yrs,60.0% (9/15) in the refractory or relapsed patients,83.3% (5/6) in the MDS transformed AML patients. The CR rates for patients with hyperprolif-erative BM and median to poor proliferative BM were 33.3% and 91.7% ,respectively(P =0.009). The median o-verall survival (OS) time of the 21 AML patients was 450 days. Two-year survival rate estimated by Kaplan-Meier Method was 30.6%. The overall median disease free survival (DFS) was 165 days. The median OS time for those refractory or relapsed was 435 days. The median OS time for those with poor cytogenetic state or standard or good cytogenetic state was 140 days and 620 days, respectively (P = 0.001). The median OS time for patients with hyperproliferative BM and median to poor proliferative BM was 321 days and 620 days, respectively (P = 0.05). The median recovery time of granulocytes above 1.0×10~9/L was 8 days. The median duration of fever was 3.5 days. The rate of infections exceeding WHO grade Ⅱ was 42.9%. No early death occurred. Conclusions The CAG induction therapy may have a higher CR rate in patients with refractory or relapsed AML, elderly AML and secondary AML from MDS transformation, and extend the median overall survival time in refractory or relapsed patients. CAG therapy can not improve the outcome of patients whose BM was in high grade proliferation state or whose cytogenetic state was poor. CAG therapy can shorten the duration of agranulocytosis and decrease the inci-dence of serious infection. Therefore, CAG therapy is worth recommending to patients who can not endure the rou-tine intensive chemotherapy.

Influence of HSP70 on combined method of hyperthermia and immunologic effector cells to treat cancer / 北京大学学报(医学版)

Objective: To investigate hyperthermia enhanced expression of heat shock protein70 (HSP70) in breast cancer drug sensitive cell line MCF7 and multi-drug resistant (MDR) cell line MCF7/ADR, so as to increase cytotoxic activity of immunologic effector cells against the target cells, and to provide an experimental basis for cell immunotherapy based on hyperthermia. Methods: The immunological effector cells were induced and expanded by cytokines. Breast cancer cell lines MCF7 and MCF7/ADR were treated at 42 ℃ for an hour. Then after being incubated for additional 4 hours, 24 hours and 48 hours, the cells were digested. Flow cytometry (FCM) was used to detect the expression of HSP70 on the target cells. MTT assay was employed to evaluate cell proliferation and the cytotoxic activity of immunologic effector cells against target cells. Results: The expressions of HSP70 in both the target cells had significant difference. The expression of HSP70 in MCF7/ADR cells was higher than in MCF7 cells before hyperthermia. After hyperthermia the expression of HSP70 increased by 6 folds in MCF7/ADR cells, and 22 folds in MCF7 cells and was higher than in MCF7/ADR cells at hour 4. The proliferation inhibition fraction of hyperthermia against MCF7 was significantly lower than that of MCF7/ADR. The cytotoxic activity of immunologic effector cells against MCF7 cells was lower than against MCF7/ADR cells before hyperthermia. After hyperthermia the cytotoxic activity of immunologic effector cells against MCF7 cells rose by 86.23%, and was higher than against MCF7/ADR cells (rose by 30.32%). Conclusion: The expression of HSP70 in breast cancer drug sensitive cell line MCF7 and MDR cell line MCF7/ADR were enhanced significantly by hyperthermia. Cytotoxic activity of immunologic effector cells against both the target cells were increased by hyperthermia. The differential expressions of HSP70 in breast cancer drug sensitive cell line MCF7 and MDR cell line MCF7/ADR affect the cytotoxic activity of immunologic effector cells.

An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.</p><p><b>METHODS</b>Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n = 9).</p><p><b>RESULTS</b>Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.</p><p><b>CONCLUSION</b>Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.</p>

Allogeneic peripheral blood stem cell transplantation in the treatment of hematologic malignancies / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the application of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in the treatment of hematologic malignancies.</p><p><b>METHODS</b>Between October 1995 and August 2001, fifty-one patients with hematologic malignancies (median age 34 years, range 5.5 approximately 52 years) received allo-PBSCT from HLA-identical (50) or 1-antigen mismatched sibling donors with conditioning regimens of TBI + CY or modified BU/CY2. Thirty-one patients were acute leukemia (AL) (15 in CR(1), 7 in CR(2) or greater, 10 in relapse including 2 relapse after allo-BMT and the other one never achieved remission); 12 chronic myeloid leukemia (CML) (CP 5, AP 2, BC 4 and relapse after allo-BMT 1); 7 MDS (RAEB 1, RAEB-T 1, AL secondary to MDS 5); Burkitt's lymphoma 1. A combination of cyclosporine and methotrexate was administered for GVHD prophylaxis.</p><p><b>RESULT</b>All patients were engrafted. The median time (range) to neutrophil >/= 0.5 x 10(9)/L and platelet >/= 20 x 10(9)/L was 14 (10 approximately 20) and 11 (7 approximately 45) days post-transplant, respectively. Grade II approximately IV acute GVHD occurred in 20/51 (39%) and grade III approximately IV aGVHD in 2 patients. Clinical chronic GVHD was diagnosed in 23 of 44 (52%) evaluable patients. Fourteen patients died: 8 died of transplant related complications, 6 of relapse. Thirty-seven patients are alive with a median follow-up of 399 (75 approximately 2 176) days, and among them 34 are in continuous complete remission, the other 3 relapsed. The 2-year probability of overall survival, disease-free survival (DFS) and relapse is 64%, 61% and 24%, respectively.</p><p><b>CONCLUSION</b>Allogeneic PBSCT is safe for both donors and recipients, and results in a rapid and stable engraftment without increase in incidence or severity of acute GVHD.</p>

Simvastatin selectively inhibits proliferation and induces apoptosis of chronic myelogenous leukemia cells / 北京大学学报(医学版)

Objective: To explore the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (the rate-limiting enzyme of cholesterol synthesis) on the proliferation and apoptosis of chronic myelogenous leukemia (CML) cells. Methods: Both normal and CML bone marrow progenitor cells were assayed in semisolid methylcellulose culture after incubation for 24 hours in suspension culture with 10 mg*L－1 simvastatin. Also, sub-G1 cells and DNA end-labeling positive cells as apoptotic cells were identified by flow cytometry after being exposed to simvastatin for 72 hours. Results: Simvastatin selectively inhibited proliferation and induced apoptosis of CML cells, but had no much influence on normal bone marrow cells. Conclusion: CML cells are more sensitive to a short-term exposure to simvastatin than normal bone marrow cells. It will be a promisingly effective chemotherapeutic agent or in vitro purging agent in autologous stem cell transplantation for the treatment of CML.