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With continuous discovery of tumor immune targets and continuous changes in antibody research and development technology, antibody drugs are becoming more and more widely used in clinical practice. However, some targets are not only expressed on tumor cells, but also on red blood cells. Therefore, the clinical application of antibodies against the corresponding targets may interfere with the detection of blood transfusion compatibility, resulting in difficulty in blood matching or delay of blood transfusion. This consensus summarizes the current solutions for the interference of CD38 monoclonal antibody (CD38 mAb) in transfusion compatibility testing. After analyzing the advantages and disadvantages of different methods, polybrene and sulfhydryl reducing agents [dithiothreitol (DTT) or 2-mercaptoethanol (2-Me)], as a solution for CD38 mAb interference in blood compatibility testing, are recommended for Chinese patients, so as to eliminate blood transfusion interference produce by CD38 mAb and further provide a pre-transfusion workflow for clinicians and technicians in Department of Blood Transfusion.
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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.
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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 (1×107/kg on day 0) and (4.0-6.8) ×107/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.
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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) ×108/kg in the PNH group and 10.81 (3.96-33.40) ×108/kg in the PNH-AA group (P=0.668) . The median doses of CD34+ cells infused were 5.00 (3.14-8.42) ×106/kg and 3.57 (1.97-6.17) ×106/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.
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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% (χ2=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% (χ2=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% (χ2=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ2=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.
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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)×108/kg in the haploidentical grafts and 2.22 (1.10-7.30)×107/kg in the cord blood units, respectively. The median doses of CD34+ cells infused were 3.49(1.02-8.89) ×106/kg in the haploidentical grafts and 0.56 (0.16-2.27) ×105/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.
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Objective@#To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML).@*Methods@#Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period.@*Results@#There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ2=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively).@*Conclusion@#DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.
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Objective@#To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group.@*Methods@#The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing.@*Results@#① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] (P<0.001) , but not for patients with CALR[57 (17-89) y] or MPL mutation[59 (22-71) y] (P>0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level (P<0.05) when compared with patients with CALR mutation or without mutations, or only significantly higher white blood cell count when compared with patients with MPL mutation (P=0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×109/L vs 800 (198-3 730) ×109/L, P<0.001]. ③Karyotype analysis was conducted in 1 160 patients with MPNs, the rates of karyotype abnormality of patients with and without CALR mutation were 9.8% (8/82) and 7.4% (80/1 078) (P=0.441) respectively; The rates of karyotype abnormality of patients with and without JAK2V617F mutation were 7.7% (75/971) and 6.9% (13/189) (P=0.688) respectively. The incidence of karyotype abnormality of patients with CALR mutation was higher than of with JAK2V617F[9.8% (8/82) vs 7.7% (75/971) ] without statistically significant difference (P=0.512) . The karyotype analysis of 7 cases of JAK2 exon12 mutation and 6 ones with MPL gene mutation revealed normal karyotype.@*Conclusions@#Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter lead to unique clinical phenotype.
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Objective@#To explore the practical value of whole-body diffusion weighted imaging (WB-DWI) in the diagnosis and monitoring of newly diagnosed multiple myeloma (MM) patients.@*Methods@#The clinical data of 107 newly diagnosed MM patients at hematology department of the first affiliated hospital of Soochow’s University from September 2012 to January 2016 were retrospectively analyzed. The results of all the 60 patients who were performed WB-DWI before treatment were analyzed. And the role of WB-DWI in the diagnosis and monitoring MM was discussed.@*Results@#Of 60 patients, 57 were found to have more or less abnormal foci of osteoclasia by WB-DWI with the positive rate of 95.0% (57/60) . Myeloma related bone lesions occurred predominantly in the axial skeleton, which were commonly seen in ribs, spines and pelvis. There were 96.5% (55/57) patients who had osteolytic rib lesions. And the ribs were the most vulnerable organs. Thirteen patients who had no osteoclasia by computerized tomography (CT) examination were detected abnormal limited diffuse lesions by WB-DWI. Eight patients underwent more than one follow-up WB-DWI. The mean apparent diffusion coefficient (ADC) values of the maximal lesions from all eight patients before and after treatment were 0.984×10-3mm2/s and 1.142×10-3mm2/s, respectively. They were both higher than the normal range [ (0.516±0.180) ×10-3mm2/s]. Mean ADC values of the maximal lesions after treatment were higher than that before treatment. The results of WB-DWI after the induction chemotherapy were consistent with clinical therapeutic effect.@*Conclusions@#WB-DWI has an important value in the diagnosis and monitoring of newly diagnosed MM. It has higher sensitivity than than that of CT. The results of WB-DWI after induction therapy has a nice correlation with treatment effect and it could monitor the disease.
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Objective To summarize the clinical features of graft failure (GF)after non-T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HCT), and to investigate the causes and treatment. Methods A retrospective analysis was carried out on 174 patientswho accepted the non-T-cell depleted Haplo-HCT from Jan 2012 to Dec 2013. The patients′ donor specific anti human leukocyte antigen antibodies (DSA) from the peripheral blood serum were detected and those DSA positive patients were treated by immunoglobulin or plasma exchange before transplatation. Results A total of three patients with acute myeloid leukemia got GF, the incidence rate was 1.72%. The patient with primary GF was given a secondHaplo-HCT, but did not get implanted with leukemia remission and three lineages persistently low , he was died of pulmonary infection eight monthes after the second transplant. One of the secondary GF patients was given peripheral blood mononuclear cells(PBMNCs) mobilized by granulocyte colony stimulating factor (G-CSF) from the donor, and got full donor chimerism on day 16 after infusion. The disease-free survival has been for 18 months. The other case was found that DSA was positive, the mean fluorescence intensity (MFI) value was 15000, then Rituximab and PBMNCs mobilized by G-CSF were administrated successively. On day 14 after infusion the partient got full donor chimerism , and MFI turned negative. The patient has been disease-free survival for 41 months. Conclusion Graft failure is a rare but fatal complication after non-T-cell depletedHaplo-HCT, Rituximab followed by PBMNCs are effective measures for DSA related GF, as were worthy of further study.
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<p><b>OBJECTIVE</b>To compare the differences between hematopoietic reconstitution and longterm prognosis of patients with severe aplastic anemia （SAA） after HLA- matched sibling donor hematopoietic stem cell transplantation（MSD-HSCT）, Haploidentical HSCT（Haplo-HSCT）, unrelated donor allogeneic HSCT（UD-HSCT）and umbilical cord blood HSCT（UCB-HSCT）.</p><p><b>METHODS</b>In this retrospective study, 63 patients with SAA who received HSCT in the First Affiliated Hospital of Soochow University between May 2008 and December 2013 were enrolled. The subjects were divided into 4 groups according to the transplantation types. The hematopoietic reconstitution, the incidence of acute graft-versushost disease（aGVHD）and 5- year survival rate after transplantation were compared.</p><p><b>RESULTS</b>All 53 subjects who received MSD-HSCT, Haplo-HSCT and UD-HSCT achieved hematopoietic reconstitution. Of them, the recovery of neutrophil and platelet were not significantly different（P<0.05）. Patients receiving UCB-HSCT had delayed recovery of hematopoiesis, and a significantly reduced reconstruction rate, when compared with those in the other 3 groups （P<0.01）. However, 4 patients undergoing UCB- HSCT presented with autologous hematopoiesis, a period of time after the failure of hematopoietic reconstitution. The expected 5- year survival rates after MSD- HSCT, Haplo- HSCT, UD- HSCT and UCB- HSCT were 70.0%, 81.0%, 88.9% and 77.8%, respectively（P>0.05）.</p><p><b>CONCLUSION</b>MSD-HSCT, Haplo-HSCT and UD-HSCT had no statistically significance in terms of hematopoietic reconstitution or prognosis. Although hematopoietic reconstitution of UCB-HSCT was lower than other transplantation types, but no significant difference in overall prognosis. So if HLA-matched sibling donor is not available, SAA patients can choose Haplo- HSCT, UD - HSCT or UCB- HSCT with comparable efficacy to MSD- HSCT, as an alternative therapy.</p>
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Idoso , Humanos , Anemia Aplástica , Sangue Fetal , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Incidência , Prognóstico , Estudos Retrospectivos , Irmãos , Doadores não RelacionadosRESUMO
<p><b>OBJECTIVE</b>To evaluate the outcomes of allogeneic hematopoietic stem cell transplantation（allo-HSCT）for paroxysmal nocturnal haemoglobinuria（PNH）and aplastic anemia（AA）- PNH syndrome.</p><p><b>METHODS</b>The clinical data of 18 PNH or AA-PNH patients, including 4 classic PNH and 14 AA-PNH, received allo-HSCT from Dec 2007 to Feb 2015 were analyzed retrospectively. Nine patients received HLA-haploidentical donor HSCT（1 patient received salvage HLA-haploidentical donor HSCT after the graft failure of double cord blood transplantation）, 7 patients received HLA-identical sibling donor HSCT, and 2 HLA-identical unrelated donor HSCT. The conditioning regimens were as follow: 13 patients received modified BU/CY- based regimens, 5 non- myeloablative regimens ［fludarabine （Flu） + antithymocyte globulin（ATG）+ cyclophosphamide（CY）or busulfan（BU）］. Prophylaxis for graft- versushost disease（GVHD）: the patients with HLA-identical sibling donor received cyclosporine（CsA）plus short-term methotrexate（MTX）, the patients with HLA -haploidentical donor or HLA-identical unrelated donor received CsA or tacrolimus（FK506）+ mycophenolate mofetil（MMF）+ short- term methotrexate （MTX）.</p><p><b>RESULTS</b>All patients were engrafted successfully（1 patient engrafted by haploidentical donor after the graft failure of double cord blood transplantation）. The median days of neutrophils（ANC）above 0.5 × 109/L and platelets （PLT） more than 20 × 10⁹/L were 11（10- 26）days and 15（11- 120）days, respectively. Three patients（17.6%）developed acute GVHD（aGVHD）, 2 for grade Ⅱ aGVHD, 1 for grade Ⅳ aGVHD. Of 16 patients, 2 occurred limited chronic GVHD（cGVHD）. After a median follow-up of 14.6（2.0-86.7）months, 3 patients（17.6%）died, out of which one died of severe aGVHD, one died of severe pulmonary infection, one pulmonary infection with transplant- associated thrombotic microangiopathy. The 5- year estimated disease free survival was（80.5 ± 10.2）%. No patient relapsed.</p><p><b>CONCLUSION</b>Allo-HSCT is an effective and curable therapy for PNH or AA-PNH with improved prognosis, and offers a valid therapeutic option for these patients before humanized monoclonal antibody against C5 are widely used clinically.</p>
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Humanos , Anemia Aplástica , Terapêutica , Soro Antilinfocitário , Bussulfano , Ciclofosfamida , Ciclosporina , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Hemoglobinúria Paroxística , Terapêutica , Metotrexato , Ácido Micofenólico , Estudos Retrospectivos , Irmãos , Tacrolimo , Condicionamento Pré-Transplante , Resultado do Tratamento , Doadores não Relacionados , VidarabinaRESUMO
<p><b>OBJECTIVE</b>To understand the prognostic value of early monitoring BCR-ABL transcripts in patients with chronic myeloid leukemia (CML) after treatment with imatinib, and to provide the information for early assessment of prognosis and treatment options.</p><p><b>METHODS</b>The clinical data of 251 patients with CML in chronic phase (CML-CP) who received imatinib as first-line therapy were retrospectively analyzed, the progression-free survival (PFS)and overall survival (OS) between different BCR-ABL transcriptional level at 3 and 6 month after imatinib treatment were compared. Meanwhile, Chi-square test and logistic regression were used to analyze the risk factors for disease progression.</p><p><b>RESULTS</b>At 3 months after imatinib treatment BCR-ABL transcriptional levels>10%, >1%-≤ 10% and ≤ 1% were found in 92, 94 and 64 patients, their PFS were 53.3%, 71.3% and 86.2%, respectively. The results showed that the PFS of patients with low BCR-ABL transcriptional levels was significantly superior to that with high BCR-ABL transcriptional levels for CML at 3 months treatment (P<0.05). The OS of three group did not reach statistical significance (92.4% vs 96.8% vs 93.8%, P> 0.05). When 182 patients received imatinib treatment at 6 months, 22 patients with BCR-ABL transcriptional levels>10%, 50>1% -≤ 10% and 110 ≤ 1%, their PFS were 27.3% vs 66.0% vs 82.7% (P<0.05), the OS of three groups were 86.4% vs 94.0% vs 100%. There were significant differences among the three groups (P<0.05). Logistic regression confirmed that the level of BCR-ABL transcriptional level at 3 and 6 months after imatinib treatment was independent factor to influence the progress of disease.</p><p><b>CONCLUSION</b>It is important for the prognosis evaluation of CML patients to monitor BCR-ABL transcriptional level at 3 and 6 months after imatinib treatment.</p>
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Humanos , Antineoplásicos , Usos Terapêuticos , Intervalo Livre de Doença , Proteínas de Fusão bcr-abl , Metabolismo , Mesilato de Imatinib , Usos Terapêuticos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Diagnóstico , Tratamento Farmacológico , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
<p><b>OBJECTIVE</b>To evaluate the efficacy of decitabine (DAC) bridging therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>The clinical characteristics and curative effect of MDS patients who received allo-HSCT from 2010 July to 2013 December were retrospectively analyzed. Of them, 25 MDS patients who received decitabine bridging allo-HSCT were randomly selected (referred to as the bridging group),while at the same time another 33 MDS patients who did not receive decitabine for allo-HSCT in MDS were also randomly selected as control group. The effect of decitabine bridging allo-HSCT on the patients' survival and occurrence of graft versus host disease (GVHD) was analyzed.</p><p><b>RESULTS</b>With decitabine bridge therapy, 64.0% patients (16/25) achieved marrow complete remission before allo-HSCT, while the control group was only 15.1% (5/33, P<0.05). Decitabine bridging group of early transplant-related mortality was lower than that of the control group (4.0% vs 18.2%), but the difference was not statistically significant (P=0.106). Up to follow-up deadline, the mortality of decitabine bridging group was 12.0%, while that of the control group was 30.3% (P<0.05). The 2-year OS of decitabine bridging group was 83.0%, while that of the control group was 59.0% (P<0.05). Of the 14 patients in decitabine bridging group with aGVHD, 7 was grade IaGVHD, 3 grade II and 4 grade III. Of the 16 patients in control group with aGVHD, 7 was grade IaGVHD, 8 grade II and 1 grade III.</p><p><b>CONCLUSION</b>Decitabine bridging therapy followed by allo-HSCT in the treatment of MDS is safe and effective.</p>
Assuntos
Humanos , Azacitidina , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Estudos Retrospectivos , Transplante HomólogoRESUMO
<p><b>OBJECTIVE</b>To investigate the role of imatinib in induction therapy for newly diagnosed adult patients with Philadephia chromosome-positive acute lymphoblastic leukemia (Ph⁺ALL), as well as the status of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of adult Ph⁺ ALL in imatinib era.</p><p><b>METHODS</b>Retrospectively analyzed 97 newly diagnosed adult Ph⁺ ALL patients from 2005 to 2013. According to whether administrated imatinib in the induction therapy and the administrating duration (≥3 d) , they were divided into imatinib (n=37) and non-imatinib group (n=60), and the former group was further divided into early-use (n=26) and late-use imatinib groups (n=11) (bounded by the fourteenth day of induction chemotherapy). We compared the overall response rate (ORR) and the negative rate of BCR-ABL fusion gene in patients who achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) among the three groups at the end of the first induction therapy. There were 44 cases underwent allo-HSCT (transplant group) and 33 cases only adopted imatinib-based chemotherapy (non-transplant group) in 77 patients who administrated imatinib as a maintenance therapy, we further compared the incidences of overall survival (OS) , disease-free survival (DFS), relapse and nonrelapse mortality (NRM) between the two groups; and dynamically monitor polymerase chain reaction (PCR) negativity of patients who were in CR1 state before transplant (n=34) at the following timepoints of achieving CR or CRi, the first consolidation therapy, beginning the pretreatment of transplant and attaining hematopoietic reconstruction after transplant.</p><p><b>RESULTS</b>After the first induction therapy, the ORR of imatinib group was significantly higher than of non-imatinib group (97.3%, 72.9% respectively, P=0.002), but early-use and late-use imatinib groups had no statistical significance in ORR (100% , 90.9% respectively, P=0.297); the rate of negativity of imatinib and non- imatinib groups were 20.0% and 0 respectively (P=0.041) in patients who achieved CR or CRi. The negative rate of patients in CR1 state before transplant attained 20.8%, 42.3%, 51.8%, 76.8%, respectively at the previously described 4 timepoints. And the differences between the fourth and the third, the third and the first timepiont all reached statistical significance (P=0.044, 0.022, respectively). The 5-year OS of transplant and non- transplant groups showed statistical difference (47.0%, 28.0% respectively, P=0.016), also for 5-year DFS (P=0.001) and the cumulative rate of relapse (P=0.000) of the former surpassing the latter; the cumulative rate of NRM between these two groups had no statistical significance (P=0.370).</p><p><b>CONCLUSION</b>Conventional induction chemotherapy in combination with imatinib in the first induction therapy of adult Ph⁺ ALL, not only improved the rate of hematologic remission, also the rate of molecular response. Imatinib used as a consolidation and maintenance therapy after remission, and allo-HSCT scheduled as soon as possible improved the prognosis.</p>
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Benzamidas , Usos Terapêuticos , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas , Mesilato de Imatinib , Cromossomo Filadélfia , Piperazinas , Usos Terapêuticos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Terapêutica , Inibidores de Proteínas Quinases , Usos Terapêuticos , Pirimidinas , Usos Terapêuticos , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
Objective To explore the efficacy of non-T cell depletion haploidentical hematopoietic stem-cell transplantation for T lymphoblastic lymphoma (T-LL). Methods 3 T-LL patients achieving complete remission received haploidentical bone marrow stem cell transplantation with granulocyte-colony-stimulating factor (G-CSF) mobilized bone marrow grafts from related donor without T-cell depletion. Two of them received a myeloablative conditioning regimen consisting of high-doses of cyclophosphamide and cytarabine with total body irradiation, whereas the other was preconditioned with busulfan, cyclophosphamide and cytarabine. All patients received strengthened phophylaxis regimen including rabbit anti-thymocyte globulin against acute graft-versus-host disease. Results All patients had rapid hematopoietic engraftment with the median time for neutrophil and platelet recovery being 12 days and 13 days, respectively. They are still alive without relapse at a median follow-up of 24 months (range: 9-75 months). Conclusion Treatment related toxicity can be acceptable in non-T cell depletion haploidenfical hematopoietic stem-cell transplantation for T-LL and the patients may achieve long term survival.
RESUMO
<p><b>OBJECTIVE</b>To study telomerase activity (TA) and its variation in bone marrow mononuclear cells from patients with myelodysplastic syndrome (MDS) at different stages in comparison with normal bone marrow cells and leukemic cells.</p><p><b>METHODS</b>The TA was semi-quantitatively determined in mononuclear cells from 20 normal bone marrow samples, 21 patients with MDS at different stages and 32 cases of acute leukemia by using a polymerase chain reaction-enzyme linked immuno-sorben assay (PCR-ELISA) kit.</p><p><b>RESULTS</b>The TA in normal bone marrow cells was in the range of 0 to 0.3 units (U) with a mean of 0.11 +/- 0.08 U. Among them, 3 samples were considered positive in accordance with the standard recommended by the kit's pamphlet. In bone marrow cells from patients with acute leukemia, the TA was ranging from 0 to 0.96 U with a mean value of 0.42 +/- 0.26 U. The positive rate was 78.1% which was significantly different from that in normal bone marrow (BM) (P < 0.01). In case of myelodysplastic syndrome, the average level of TA was 0.27 +/- 0.19 U (ranging from 0 to 0.97 U) with a positive rate of 66.7%. In comparison with normal BM cells, the difference was significant (P < 0.05). Particularly, the MDS high-risk subgroup exhibited a significantly higher activity of telomerase (P < 0.05). In comparison with INT-1 and INT-2 subgroups in MDS patients based on international prognostic scoring system (IPPS), the difference in TA was also significant (P < 0.05). The abnormality in cell karyotype was not correlated with TA.</p><p><b>CONCLUSION</b>The normal bone marrow cells demonstrate TA at a marginal level while a remarkably increasing level may be seen in acute leukemia patients. The BM cells from MDS patients display a moderate TA among which the high risk MDS subgroup with a poor prognostic IPPS score exhibited markedly higher TA.</p>