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<p><b>OBJECTIVE</b>To investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance.</p><p><b>METHODS</b>A total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used.</p><p><b>RESULTS</b>All the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%).</p><p><b>CONCLUSION</b>These data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.</p>
Assuntos
Humanos , Soro Antilinfocitário , Usos Terapêuticos , Bussulfano , Usos Terapêuticos , Ciclosporina , Usos Terapêuticos , Doença Enxerto-Hospedeiro , Antígenos HLA , Genética , Neoplasias Hematológicas , Terapêutica , Transplante de Células-Tronco Hematopoéticas , Incidência , Leucemia , Terapêutica , Ácido Micofenólico , Usos Terapêuticos , Transplante de Células-Tronco , Doadores de Tecidos , Condicionamento Pré-Transplante , Transplante Homólogo , Vidarabina , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To study the significance of flow cytometric monitoring minimal residual diseases (MRD) in patients with acute leukemia (AL) after allogeneic hemapoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>From January 2007 and January 2008 MRD were detected by flow cytometry (FCM) in 402 bone marrow (BM) in 102 AL patients without leukemic gene and chromosomal changes at first diagnosis after HSCT (1, 2, 3, 6,12 months after HSCT; adding detection frequency in part of high risk patients), The relationship between the MRD results and clinical prognosis were observed. Patients with significantly higher MRD were treated and the effectiveness was monitored by FCM (MRD > 0.01% considered as positive).</p><p><b>RESULTS</b>(1) 71 cases were persistently negative for MRD after HSCT and all them were in hematologic complete remission (CR). Only 3 cases had extramedullary relapse. The disease free survival (DFS) and overall survival (OS) were 66.2% and 90.1%, respectively. (2) Of 27 MRD(+) cases 11 converted to MRD negativity after chemotherapy plus donor lymphocyte infusion (DLI), CIK, NK cells. The DFS and OS were 63.6% and 72.7%, respectively. Other 16 cases had hematologic relapse. The DFS and OS were 11.1% and 25.0%, respectively. The median time from MRD increasing to hematologic relapse was 48 days (7-69 day). (3) Four cases had hematologic relapse after HSCT and died in the end.</p><p><b>CONCLUSIONS</b>(1) The DFS and the OS in MRD(-) cases are significantly higher than those of MRD(+) cases. (2)MRD(+) patients after HSCT coveted to MRD(-) after intervention. Therapy, whose DFS and the OS are still significantly higher than those of MRD(+) cases. (3) Patients with hematologic relapse after HSCT have the worst prognosis and the DFS and OS are significantly low. FCM monitoring of MRD in patients after HSCT is a sensitive, specific, quick and simple method. It can indicate recurrent state in time, facilitates early intervention, reduces the hematologic relapse risk and improves DFS.</p>
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Leucemia , Cirurgia Geral , Neoplasia Residual , Diagnóstico , Período Pós-Operatório , Estudos Retrospectivos , Transplante Homólogo , Resultado do TratamentoRESUMO
This study was purposed to analyze the characteristics of morphology, immunology, cytogenetic and molecular biology of leukemia cells in 12 AML patients with Ph(+) and their correlation with survival of patients. 12 patients with Ph(+) AML were diagnosed according to diagnostic criteria of WHO and existence of t(9;22) (q34;q11) or t(9;22) abnormality, meanwhile no evidence of CML chronic phase was observed. The results showed that 8 out of 12 cases were confirmedly diagnosed to be AML by morphologic and immunophenotypic examination, 4 cases were diagnosed as myeloid and B lymphocytic mixed acute leukemia. The Ph chromosome was detected in 10 cases by chromosome analysis at the first time of diagnosis, and some of the cases had coexistence of complex chromosome and/or normal karyotype. BCR-ABL transcript was detected in all 12 cases, including 7 cases with b3a2, 1 case with b2a2, 1 case with b2a2 variants, 2 cases with e1a2 and 1 case with e18a2. The 12 cases all got complete remission after chemotherapy and/or gleevec treatment, out of them 3 cases received chemotherapy and gleevec treatment, but 2 cases died; 9 cases received allogeneic hematopoietic stem-cell transplantation (allo-HSCT), 1 case died from relapse, among them 1 case died from transplant complications. The median survival was 24 (8 - 80) months, the overall survival of 3 years was (51.4 ± 17.7)%. It is concluded that the Ph(+) AML is a acute myelogenous leukemia with poor prognosis, but long-term survival may be achieved with HSCT as quick as after complete remission from gleevec and chemotherapy treatment. Meanwhile, the detection of BCR-ABL gene and it variants may be give more opportunity for diagnose and treatment, which can be used as routine screening for newly diagnosed leukemia.
Assuntos
Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva , Diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Diagnóstico , PrognósticoRESUMO
<p><b>OBJECTIVE</b>To evaluate the efficacy of salvaged allogeneic hematopoietic stem cell transplantation (allo-HSCT) for refractory/recurrent acute myeloid leukemia (AML).</p><p><b>METHODS</b>A total of 45 patients with refractory/recurrent AML were enrolled from September 2006 to April 2010. The median blasts in bone marrow (BM) were 36% (20% to 92%) before conditioning. The donors were identical siblings (6) or unrelated ones (9) or haploidentical family members (30). Conditioning regiments were individualized according to patients' status, the regimen with high-dose cytarabine plus BuCy/CY was mostly used (20). The patients with impaired organ function received above regimen except using fludarabine instead of cyclophosphamide (16). FLAG followed by reduced-intensified BuCy was employed for the recipients with more than 40% blasts in BM (6) to reduce leukemia burden. TBI/CY or TBI/Fludarabine was used for the recipients with extramedullary infiltration of leukemia or multidrug resistant leukemia. G-CSF, MTX, NVT, Vm26, Acla or Thaltipa was added into conditioning regiments according to leukemia character.</p><p><b>RESULTS</b>All but 2 patients attained durable engraftment. The incidence of grade II to IV aGVHD and cGVHD were 34%, 59.1%, respectively. With median follow-up 30 (0.5 - 57) months, the relapse rate was 29.2%. Twenty-nine of 45 (60.2%) patients remained in complete remission since salvaged HSCT. Three-years disease-free survival and overall survival were 60.2% and 62.6%, respectively.</p><p><b>CONCLUSION</b>Our results indicated that the combination of salvaged HSCT with prophylactic immunotherapy might be a promising modality for treatment of refractory/recurrent AML, even with high leukemia burden.</p>
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Transplante de Células-Tronco Hematopoéticas , Métodos , Leucemia Mieloide Aguda , Mortalidade , Terapêutica , Recidiva , Taxa de Sobrevida , Condicionamento Pré-Transplante , Métodos , Resultado do TratamentoRESUMO
<p><b>OBJECTIVE</b>To study the predictable value of monitoring minimal residual disease (MRD) regularly by flow cytometry (FCM) in patients with acute leukemia (AL) in the first complete remission (CR(1)).</p><p><b>METHODS</b>From April 2005 to July 2009, AL patients who had got CR(1) after chemotherapy were regularly monitored for MRD in bone marrow by FCM to relapse or to July 2010 in Beijing Daopei Hospital (not including those received stem cell transplantation). The special antibody combinations were employed for each patient according to aberrant expression of leukemia cells. MRD(+) was defined as the aberrant cells more than 0.01%. The probability of continuous CR (CCR) was calculated by Kaplan-Meier formula, and the statistical difference between two CCR probabilities was evaluated by log-rank test.</p><p><b>RESULTS</b>A total of 163 AL patients in CR(1) were monitored to relapse or to July 2010. Among 89 AML patients referred to our hospital within 1 year after diagnosis, 30 cases were in MRD(+) and 59 cases MRD(-) till 12 months following chemotherapy, 3/30 patients in MRD(+) and 47/59 remained in CCR to July 2010. The probability of CCR at 24, 36 months was 13%, 13%in MRD(+) group, 94%, 78% in MRD(-) group respectively, the difference between them was statistically significant (P < 0.01). Among 35 ALL referred to our hospital within 5 months after diagnosis, 13 cases were MRD(+) and 22 cases MRD(-) till 5 months following chemotherapy, 0/13 patients in MRD(+) and 20/22 patients in MRD(-) remained in CCR to July 2010. The probability of CCR at 24, 36 months was 0% in MRD(+) group, 96%, 96% in MRD(-) group respectively, the difference between them was statistically significant (P < 0.01). Over the time point above, all patients with MRD(+) or their MRD from negative to positive relapsed finally, and most patients with MRD(-) remained CCR to July 2010.</p><p><b>CONCLUSION</b>It had a clinical prognostic value to monitor MRD regularly by FCM in the patients with AL after CR(1).</p>
Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Citometria de Fluxo , Leucemia Mieloide Aguda , Diagnóstico , Patologia , Neoplasia Residual , Diagnóstico , Valor Preditivo dos Testes , Prognóstico , RecidivaRESUMO
<p><b>OBJECTIVE</b>To analyse the clinical features, diagnostic methods and risk factors of cytomegalovirus (CMV) enteritis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Analysis was made on 24 cases of CMV enteritis after allo-HSCT in Beijing Daopei Hospital from Aug. 2007 to Jul. 2009, including clinical data, endoscopic diagnosis, histopathological and virological results, and the association between CMV enteritis with viremia and graft-versus-host disease(GVHD).</p><p><b>RESULTS</b>87.5% of the patients were over 18 years old. The median time to diagnosis of CMV enteritis was 63 days after HSCT. The mucosal lesions in enteroscopic examination had no significant differences between CMV enteritis and gastrointestinal GVHD complicated with the enteritis. The methods used in diagnosis included histopathology (32.1%) and virology (92.9%). The copies of CMVDNA in mucosal samples greater than 10(5)/10(6) PBNC was better diagnosis. A number of risk factors were compared between the survival and death groups: type of transplant, conditioning regimen, the time span of ganciclovir prophylaxis therapy, grade II-IV GVHD before enteritis, the time of diagnosis as GVHD, using MP > or = 1 mg/kg to treat GVHD, the time between GVHD and enteritis, CMV viremia before enteritis, the time of diagnosis as enteritis, CMVDNA quantitation, and there were no any statistic differences.</p><p><b>CONCLUSION</b>Cytomegalovirus enteritis should be carefully diagnosed by histopathology and virology through endoscopic examination. It is better to undertake pan-colon endoscopy as well as terminal ileum examination for more accurate diagnosis. PCR can significantly improve the detection rate. CMVDNA detection in patients' stool may be helpful to diagnosis, especially for those patients who can not stand the endoscopy examination.</p>
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Citomegalovirus , Infecções por Citomegalovirus , DNA Viral , Enterite , Virologia , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Fatores de RiscoRESUMO
<p><b>OBJECTIVE</b>To analyze the clinical and laboratory features of 9 cases of gammadeltaT cell lymphoma or leukemia.</p><p><b>METHODS</b>From 2007 to 2011, 9 patients with gammadeltaT-cell lymphoma/leukemia were diagnosed in our hospital. The immunophenotype of the abnormal cells were detected by flow cytometry, clonal gene rearrangement of IgH, TCRgamma, TCRdelta by PCR, chromosome karyotype analysis by G banding, acute leukemia gene and the DNA of type 1 - 8 human herpes virus by multiple nested PCR, The gammadeltaT cells were determined by T cell with TCR gammadelta chain, the malignant gammadelta T cells by the abnormal expression of T cell antigens and the precursor malignant gammadelta T cells by the expression of CD34, TDT, CD99, CD1 a or acute leukemia genes.</p><p><b>RESULTS</b>In the 9 patients with gammadeltaT cell lymphoma leukemia, significant malignant gammadeltaT cells infiltration of bone marrow were found in 8 with blast morphology. 5 were diagnosed as T-ALL/LBL (gammadeltaT type) and 4 HSgammadelta TCL. The clonal gene rearrangement of TCRgamma and/or TCRB were detected in 6/6 patients. Patients either did not achieve complete remission(CR) after induction therapy or relapsed quickly after CR. Only 4/5 patients remained continuous CR(CCR) at 2, 2, 3,12 months respectively, after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the fifth T-ALL (gammadeltaT) relapsed 1 month after allo-HSCT.</p><p><b>CONCLUSIONS</b>The incidence of gammadelta T cell lymphoma or leukemia may be higher than reported, part of them were T-ALL/LBL with poor prognoses. FCM and clonal gene rearrangement of TCRgamma and/or TCRdelta are helpful to diagnosis. Allo-HSCT may be the only curative approach.</p>
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Citometria de Fluxo , Imunofenotipagem , Cariótipo , Leucemia de Células T , Diagnóstico , Genética , Linfoma de Células T , Diagnóstico , Genética , Receptores de Antígenos de Linfócitos T gama-delta , GenéticaRESUMO
This study was aimed to analyze the clinical and cytogenetic characteristics of acute leukemia with 11q23/mll rearrangement and explore the reasonable therapeutic principles. Characteristics in general situation, morphology, immunology, molecular biology, cytogenetics, treatment and overall survival of 36 cases of acute leukemias with mll gene rearrangement were studied and analyzed. The results showed that 36 cases with mll gene rearrangement were found positive (7.2%) in 494 patients with acute leukemia. Among the 36 cases of mll rearrangement positive, 32 cases were diagnosed as acute myeloid leukemia (AML) with myeloid antigen expression, of which 5 cases expressed lymphoblastic differentiation antigen; 4 cases were classified as B-lineage acute lymphoblastic leukemia (ALL), of which non-lineage myeloid expression pattern were found in 3 cases. In 29 out of 36 cases (80%) the clonal chromosomal aberration were detected, of which chromosome 11 aberration were observed in 22 cases. All patients received chemotherapy with a total response rate of 47.2%. Of the responded patients, 10 cases relapsed within 6 months, with a recurrence rate of 40%; 9 cases received hematopoietic stem cell transplantation (HSCT), 7 cases of which survived after transplantation. The median survival time of 36 cases was 16 months (range 2 - 46) and their 2-year overall survival rate was 41.4%. The 2-year overall survival rate of 9 patients who received HSCT was 87.5%. It is concluded that acute leukemia patients with mll gene rearrangement show poor response to chemotherapy, high recurrence rate and poor prognosis. Hematopoietic stem cell transplantation may be a reasonable treatment principle to improve these patients' survival situation.
Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Transplante de Células-Tronco Hematopoéticas , Histona-Lisina N-Metiltransferase , Leucemia , Classificação , Diagnóstico , Genética , Terapêutica , Leucemia Mieloide Aguda , Diagnóstico , Genética , Terapêutica , Proteína de Leucina Linfoide-Mieloide , Genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Diagnóstico , Genética , Terapêutica , Prognóstico , Taxa de SobrevidaRESUMO
<p><b>OBJECTIVE</b>To explore the efficacy of tumor-ablative individualized allogeneic hematopoietic stem cell transplantation for the treatment of patients with high risk/refractory leukemia.</p><p><b>METHODS</b>Fivety-seven patients with high risk/refractory leukemia were enrolled. Tumor-ablative individualized conditioning regimens included HDAra-C + Bu/Cy, Ara-C + Bu/Fludarabine, G-CSF primed HDAra-C + Bu/Cy, and FLAG followed by reduced-intensified BuCy. Overall survival (OS), disease free survival (DFS), graft versus host disease, infection and relapse post grafting were analyzed.</p><p><b>RESULTS</b>Fifty-six patients attained durable engraftment. The median follow-up duration was 17.5 (2 - 34) months. The 18 months probabilities of OS and DFS were (74.7 ± 6.1)% and (62.4 ± 6.7)%, respectively. In addition, the 18 months probabilities of OS and DFS in patients who attained complete remission (CR) before transplantation were (74.2 ± 7.1)% and (58.8 ± 8.1)%, respectively, while in those not attained CR were (77.0 ± 11.8)% and (72.7 ± 11.7)%, respectively. Twenty nine patients developed acute GVHD (aGVHD) (grade I in 18, grade II in 4, grade III in 2 and grade IV in 5). The probabilities of aGVHD was (50.9 ± 6.6)% by Kaplan-Meier curve analysis. The probabilities of grades 2-4 and grades 3-4 aGVHD were (19.3 ± 5.2)% and (12.3 ± 4.3)% respectively. Extensive chronic GVHD (cGVHD) was observed in 36 patients. The probabilities of cGVHD was (64.3 ± 6.4)% by Kaplan-Meier curve analysis. Cytomegaloviremia (CMV) was observed in 39 (68.42%) patients, hemorrhagic cystitis in 13 (22.8%) patients, fungous infection in 16 (28.07%) patients and bacterial infection in 38 (66.67%) patients. Relapse occurred in 14 patients (hematologic relapse in 11 and extramedullary relapse in 3), probabilities of relapse being (24.6 ± 5.7)%. The 17.5-month probability of relapse in patients who attained CR before transplantation was (28.1 ± 7.7)%, while in those not attained CR was (15.6 ± 10.2)%. Fifteen patients died (6 from hematological relapse, 5 from infection of bacterial and fungous, 4 from cGVHD) after 100 days.</p><p><b>CONCLUSION</b>Tumor-ablative individualized allogeneic hematopoietic stem cell transplantation is a promising and safe choice for treatment of high risk/refractory leukemia, even with high leukemia burden.</p>
Assuntos
Humanos , Citarabina , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia , Condicionamento Pré-TransplanteRESUMO
The invasive fungal infections (IFI) in immunocompromised patients are associated with a high mortality rate and diagnostic difficulty. Serological methods such as aspergillus galactomannan assay (GM test) and (1, 3)-beta-D glucan (BG) assay (G test) can be used as an adjunctive method for IFI diagnosis based on their characteristics of easy-operating, rapidness and high sensitivity. Compared with GM test, G test can be more widely used except for the diagnosis of aspergillosis. The purpose of this study was to investigate the value of G test in the diagnosis of IFI in patients with hematological disorders. The plasma was collected from 162 suspected IFI patients with hematological disorders in Beijing Daopei Hospital, including 85 patients after chemotherapy and 77 patients after stem cell transplantation from May 2007 to May 2008, BG level was measured with MB-80 Microbiology Kinetic Rapid Reader and the measured results together with the clinical characteristics were retrospectively analyzed. According to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, there were 2 patients diagnosed as proven IFI, 18 as probable IFI, 75 as possible IFI and 67 as no IFI. The results showed that at a cutoff of 20 pg/ml, the sensitivity and specificity of G test were 75% and 91% respectively, with a positive predictive value (PPV) of 71.4% and a negative predictive value (NPV) of 92.4%. 51 out of the 75 possible IFI patients with elevated BG level were responsive to antifungal treatment but non responsive to broad-spectrum antibiotics, retrospectively were diagnosed as IFI, suggesting that G test improved the IFI diagnostic rate by 31.4%. In conclusion, G test is a rapid and simple method for early diagnosis of IFI in patients with hematological disorders.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doenças Hematológicas , Sangue , Diagnóstico , Microbiologia , Micoses , Sangue , Diagnóstico , Plasma , Química , beta-Glucanas , SangueRESUMO
Natural killer (NK)/T-cell lymphomas represent a rare type of lymphoma derived from either activated NK cells or cytotoxic T cells. They are most commonly extranodal and tend to present as destructive lesions within the midline facial structures. Other than the nasal cavity and Para nasal sinuses, several other extra nodal sites of involvement have been reported, including the pharynx, gastrointestinal tract, and testis. Occasionally, pleural effusion has also been observed. Here, a case of lymphoma of NK/T-cell type presented as pleural effusion was reported. The patient was previously misdiagnosed as B cell non-Hodgkin's lymphoma by pathological and immunohistochemistry (IH) analysis for pleural membrane biopsy specimen. After the analysis of the pleural fluid cells by a combination of morphologic, immunophenotypic, cytogenetic and molecular (MICM) methods in Beijing Dao-Pei hospital, some lymphoblasts were found morphologically, which expressed cytoplasmic CD3 (cCD3) and CD56 by flow cytometry analysis and had a clonal T-cell receptor gamma (TCR-gamma) gene rearrangement by molecular analysis, so that the diagnosis was finally corrected as NK/T-cell lymphoma and an allogeneic stem cell transplantation was successfully performed. In conclusion, this unusual case highlights the significance of MICM combined techniques for the diagnosis of lymphoma, as well as an unusual presentation of a rare disease and the successful treatment.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Técnicas Citológicas , Linfoma Extranodal de Células T-NK , Diagnóstico , Células T Matadoras Naturais , Derrame Pleural , DiagnósticoRESUMO
To investigate the biological characteristics of the variant translocation der ins (17;15) in a patient with acute promyelocytic leukemia (APL), the conventional G-banding technique, interphase fluorescence in situ hybridization (int-FISH), RT-PCR, gene scanning, gene sequence and flow cytometry were performed. The results indicated that the variant translocation der ins (17, 15) observed by G banding technique was a rare type, the int-FISH assay by using dual-color pml/raralpha fusion probes confirmed the cytogenetic findings. The detection results of other molecular methods demonstrated the existence of the whole pml/raralpha fusion gene, while this case had insertion variant translocation. This patient got complete remission by using combined chemotherapy, and survives with continuous complete remission during following up for 1 year. In conclusion, the variant translocation der ins (17; 15) is rare type in APL, its incidence is lower, several signal types in detection of int-FISH were observed and the combination chemotherapy for this patient showed more obvious efficacy.
Assuntos
Humanos , Masculino , Adulto Jovem , Bandeamento Cromossômico , Cromossomos Humanos Par 15 , Cromossomos Humanos Par 17 , Hibridização in Situ Fluorescente , Métodos , Interfase , Genética , Leucemia Promielocítica Aguda , Genética , Translocação GenéticaRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only proven curative therapy for chronic myeloid leukemia (CML), but lack of human leukocyte antigen (HLA)-matched sibling or unrelated donors has restricted its application. Recently, we developed an effective method for haploidentical allo-HSCT achieving comparable outcomes to HLA-identical transplantation. AIM: To evaluate the outcomes of CML patients who underwent haploidentical allo-HSCT. METHODS: Ninety-three patients were treated with a modified busulfan (BU)/cyclophosphamide (CY) 2 regimen, including antithymocyte globulin followed by unmanipulated blood and marrow transplantation. RESULTS: Our data showed that the cumulative incidence of acute graft-versus-host disease (GVHD) was 64.52%, and grade III-IV was 26.45%, 61.79% had chronic GVHD, and 28.93% had extensive chronic GVHD. Non-relapse mortality varied at 8.72% (100 days), 20.72% (1 year) and 20.72% (2 years). Probability of 1-year and 4-year leukemia-free survival was similar in chronic phase (CP) 1, CP2/CR2, accelerated phase, and blast crisis patients. Probability of 4-year overall survival varied as 76.5% (CP1), 85.7% (CP2/CR2), 73.3% (accelerated phase), and 61.5% (blast crisis). Multivariate analysis indicated that factors affecting transplantation outcomes were HLA-B+DR mismatches versus others for II-III acute GVHD and III-IV acute GVHD, the stage of disease at transplantation for relapse, and the time from diagnosis to transplantation for leukemia-free survival, overall survival, and transplantation-related mortality. In our protocol, survival of HSCT for advanced CML was similar to stable stage. CONCLUSIONS: For patients lacking an HLA-identical related donor, haploidentical relatives are alternative HSCT donors.
Assuntos
Crise Blástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Criança , Doação Dirigida de Tecido , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas , Análise de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto JovemRESUMO
<p><b>OBJECTIVE</b>To explore the immunophenotypic characteristics of CD7 and/or CD56 positive acute myeloid leukemic stem cells, and the relationship between minimal residual disease (MRD) and the leukemic stem cells (LSC).</p><p><b>METHODS</b>The immunophenotype of leukemia cells from 51 CD34+ CD38+ CD7+ and/or CD34+ CD38+ CD56+ acute myeloid leukemia (AML) patients (exclude M3) at diagnosis was analyzed by using 4 - 6 panels of 4 color antibodies, and cells from 28 normal bone marrow (NBM) samples were served as control. The expression of CD7 and CD56 in the CD34+ CD38+ subpopulation was used as a leukemic cell marker for monitoring MRD of 53 samples from 26 CD7+ and (or) CD56+ patients.</p><p><b>RESULTS</b>In CD7+ and/or CD56+ AML patients at diagnosis, the average positivity of CD7 in CD34+ CD38+ subpopulation and CD34+ CD38- Lin- stem cells subpopulation was (77.39 +/- 20.71)% and (44.57 +/- 22.70)%, and that of CD56 was (56.71 +/- 32.56)% and (33.51 +/- 29.64)%, respectively, all significantly higher than that of NBM (P < 0.01 and P < 0.05). Compared with that of NBM, the expression of CD90 in AML patients was significantly lower in the CD34+ CD38- Lin- subpopulation (P < 0.01), the expression of CD123 was significantly higher than NBM (P < 0.01), and the expression of CD117 was no significant difference (P > 0.05). In follow up of CD7+ and (or) CD56+ patients, the expression rate of CD7 and (or) CD56 in the CD34+ CD38- Lin- subpopulation MRD+ group was significantly higher than that in the MRD- group. The actual rate for CD7 was 71% (15/21) and 16% (4/25) (P = 0.001), and its relative rate was 81% (17/ 21) and 24% (6/25) (P = 0.000), respectively. The actual rate of CD56 is 100% (4/4) and 12% (3/25) (P = 0.001), and its relative rate was 75% (3/4) and 20% (5/25) (P = 0.031), respectively. A high CD7+ CD34+ CD38- Lin- subpopulation frequency at diagnosis in CD7+ AML patients predicted a high frequency of positive MRD in later detection (P < 0.05).</p><p><b>CONCLUSIONS</b>CD7 and CD56 are expressed on the stem cells in CD7+ and/or CD56+ AMLs and a high frequency of CD7 and CD56 in the CD34+ CD38- Lin- stem cell subpopulation predicts a high frequency of positive MRD in later detection.</p>
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos CD7 , Genética , Antígeno CD56 , Genética , Seguimentos , Células-Tronco Hematopoéticas , Alergia e Imunologia , Imunofenotipagem , Leucemia Mieloide Aguda , Diagnóstico , Genética , Alergia e Imunologia , Neoplasia Residual , Diagnóstico , Genética , Alergia e Imunologia , Células-Tronco Neoplásicas , Alergia e ImunologiaRESUMO
This study was to investigate the relationship between Clostridium difficile associated diarrhea (CDAD) and intestinal microecosystem in patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to clarify clinical characteristics of intestinal microecosystem disorder. Clostridium difficile (CD) was isolated and identified by enzyme-linked-immunosorbent assay using clostridium difficile Premier toxins A&B Kit and anaerobic culture in 44 cases with diarrhea. Fecal flora (bifidobacteria, lactobacillus, bacteroides, peptostreptococcus, Clostridium perfringens, enterobacteriaceae, enterococcus, and yeasts) of patients were quantitatively and qualitatively analyzed by Mitsuoka's methods. The results showed that CDAD occurred after using antibiotic or chemotherapy. Clostridium difficile was detected in 12 patients with diarrhea (positive rate was 27.27%). There was marked changes of intestinal microecosystem when patients suffered from CDAD. The number of lactobacillus, bifidobacteria, bacteroides, enterobacteriaceae and so on decreased significantly. It was effective to treat CDAD with vancomycin, metronidazole and probiotic, but the recurrence rate was 16.67%. In conclusion, CDAD complicated by allo-HSCT is related to change of intestinal microecosystem. While treating CDAD with the sensitive antibiotic, the intestinal flora of patients should be supported actively. This treatment contributes to improving disease status and reducing diarrhea recurrence.
Assuntos
Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antibacterianos , Usos Terapêuticos , Infecções por Clostridium , Microbiologia , Clostridioides difficile , Diarreia , Microbiologia , Neoplasias Hematológicas , Terapêutica , Transplante de Células-Tronco HematopoéticasRESUMO
The aim of this study was to investigate the expanding capacity of bone marrow-derived mesenchymal stem cells (MSCs) in 34 patients who received a marrow and/or peripheral blood stem cells transplant (SCT). Marrow samples were obtained from iliac crest aspirates of healthy individuals (normal controls) and patients for the isolation, purification, and expansion of MSCs. The different passage MSCs of patients were analyzed by flow cytometry (FCM) to reveal the cell surface antigen expression. The expanding function of MSCs from patients after SCT, which might be affected by cytotoxic therapy in the conditioning regimen, colony-forming unit-fibroblast (CFU-F), confluent time, and passage number of the culture were measured, and then compared with those in the normal controls. At the same time, the numbers of colony-forming unit of hematopoietic progenitor were detected and compared with normal controls. In addition, CFU-F, confluent time, and passage number of MSCs were compared between group of BMSCs plus PBSCs co-transplanted patients and group of BMSCs plus PBSCs with the second donor umbilical cord blood cells (UBCs) co-transplanted patients. The results indicated that a confluent monolayer of stroma cells was generated in 31 out of the 34 cases (91.1%), a subconfluent monolayer was generated in one case (2.9%), no adherent stromal layer was generated in 2 cases (5.9%). As compared with the normal controls, the time generating a confluent layer of stroma cells from primary MSCs of patients was longer significantly, and the passage number and CFU-F of MSCs of patients in vitro was less than that of normal controls significantly. Compared with the group of BMSCs plus PBSCs co-transplanted patients, the confluent time of MSCs in group of BMSCs plus PBMSCs with UBCs co-transplanted patients was shorter, the passage number and CFU-F count in this group were higher. It is concluded that the MSCs of patients after HSCT are damaged, and the co-transplant of BMSCs and PBSCs plus UBCs can partially improve in vitro expanding capacity of MSCs from patients.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Células da Medula Óssea , Patologia , Proliferação de Células , Células Cultivadas , Sangue Fetal , Biologia Celular , Transplante , Neoplasias Hematológicas , Patologia , Terapêutica , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Biologia Celular , Células-Tronco Mesenquimais , Patologia , Transplante de Células-Tronco de Sangue PeriféricoRESUMO
To investigate the cytogenetic and clinical characteristics of inv(3q) (q21q26) and t(3;3) (q21; q26) aberrations as well as prognosis, cases were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, while G-banding technique was used to perform karyotyping. The results showed that the simple inv(3q) and t(3; 3) aberrations were rare, they commonly combined with other chromosome aberrations such as -7/7q- and t (9; 22). The involved diseases included myelodysplastic syndromes, acute myeloid leukemia and chronic myelogenous leukemia in blast crisis. Out of 24 patients, 2 patients diagnosed with M(5) subtype did not achieve complete remission after multiple chemotherapy; 2 patients received allogenic stem cell transplantation relapsed. It is concluded that 3q21q26 aberration commonly combined with chromosome aberration 7/7q-, for these patients the efficacy of chemical therapy is poor, the efficacy of bone marrow transplant is too poor, these patients with inv(3q) and t(3; 3) aberrations have poor prognosis and short overall survival.
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Inversão Cromossômica , Cromossomos Humanos Par 3 , Genética , Cromossomos Humanos Par 7 , Genética , Leucemia Mielogênica Crônica BCR-ABL Positiva , Genética , Leucemia Mieloide Aguda , Genética , Síndromes Mielodisplásicas , Genética , Prognóstico , Translocação GenéticaRESUMO
<p><b>BACKGROUND</b>Allogeneic stem cell transplantation is a potential curative approach in patients with multiple myeloma. The very high transplant related mortality associated with standard allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative treatment modality. The challenge for clinical investigators is to reduce the incidence of post-transplant complications for patients receiving autologous hematopoietic stem cell transplantion for multiple myeloma. In this study the toxicity and efficacy of modified myeloablative conditioning regimen followed by allogeneic stem cell transplantation was investigated in patients with multiple myeloma.</p><p><b>METHODS</b>The conditioning regimen consisted of hydroxyurea, cytarabine, busulfan, cyclophosphamide, and semustine. Ten patients underwent allogeneic transplantation among them hydroxyurea (40 mg/kg) was administered twice on day-10 and cytarabine (2 g/m(2)) was given on day-9, busulfan was administered orally in four divided doses daily for 3 days (days-8 to -6). The dose of busulfan was 12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour on days-5 and -4 (1.8 g/m(2)), and with semustine (Me-CCNU) 250 mg/m(2) on day -3.</p><p><b>RESULTS</b>Chimerism data were available on all patients and all patients achieved full donor chimerism without graft failure. Six patients had not acute graft-versus-host disease (GVHD, 36.4%; 95% CI: 13.9% - 38.6%). Two patients (18.2%) developed grade I acute GVHD (95% CI: 10.9% - 35.9%) and grade II acute GVHD occurred in one patient (9.1%; 95% CI: 8.4% - 32.3%). Severe grade IVa GVHD was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD was 22.2% (95% CI: 11.7% - 36.7%), among them one died of severe grade IV GVHD and one developed multiorgan failure on day +170; the treatment-related mortality was 22.0% (95% CI: 10.3% - 34.1%). The overall 4-year survival rate was 67.8% (95% CI: 16.3% - 46.7%). The estimated 4-year progression-free survival rate was 58.5% (95% CI: 13.7% - 41.8%). The 4-year complete remission was 72.7% (95% CI: 27.8% - 49.6%). One patient relapsed after 4 months and achived the complete remission after receiving the donor lymphocyte infusion.</p><p><b>CONCLUSIONS</b>Modified conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells + bone marrow cells transplantation result in a low incidence of severe GVHD with a relatively low treatment-related mortality, high complete remission rates and a long-term survival.</p>
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bussulfano , Ciclofosfamida , Doença Enxerto-Hospedeiro , Epidemiologia , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Mortalidade , Terapêutica , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
<p><b>OBJECTIVE</b>To study the correlation between polyoma virus load and hemorrhagic cystitis after allogeneic stem cells transplantation for prevention of hemorrhagic cystitis.</p><p><b>METHODS</b>Blood and urine specimens were collected from 40 healthy persons, 40 patient with stem cells transplantation and 20 cases complicated with hemorrhagic cystitis for determination of VP1 gene of polyomaviruses BK virus (BKV)/Jamestown Canyon virus (JCV) and simian virus 40 (SV40) by polymerase chain reaction (PCR) and EvaGreen stain fluorescence quantitative assay.</p><p><b>RESULTS</b>In the peripheral blood, all genes of BKV/JCV and SV40 were negative, while BKV gene in urine and blood from healthy persons and patient with stem cells transplantation was 15% (6/40) and 100% (40/40), respectively. The gene of JCV was positive in 10% (4/40) and 12% (5/40), the gene of SV40 was negative.</p><p><b>CONCLUSION</b>Genes of BKV and JCV was detectable in urine specimens of healthy persons and there was a correlation between the load of polyomavirus and incidence of hemorrhagic cystitis.</p>
Assuntos
Humanos , Proteínas do Capsídeo , Genética , Cistite , Diagnóstico , Virologia , DNA Viral , Sangue , Genética , Urina , Transplante de Células-Tronco Hematopoéticas , Hemorragia , Diagnóstico , Virologia , Reação em Cadeia da Polimerase , Métodos , Polyomavirus , Genética , Infecções por Polyomavirus , Virologia , Carga ViralRESUMO
The aim of study was to investigate the importance of chromosome aberration in differential diagnosis of eosinophilia and the chromosomal aberrations involved in patients with clonal eosinophilia. 65 cases of eosinophilia were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, and G-banding technique was used for karyotyping. The results showed that out of 65 cases, chromosome 16 inversion was detected in 9 patients suspected as M(4Eo), and among the other 56 cases, 5 were detected with chromosomal aberrations (8.9%). Combining clinical, hematological and cytogenetical data, the 5 patients were diagnosed as acute myeloid leukemia with eosinophilia, chronic eosinophilic leukemia, 8p11 myeloproliferative syndrome, chronic myeloid leukemia in acute phase and acute myeloid leukemia-M(4Eo) respectively. The detected chromosomal aberrations were +14, t (5; 12) (q31; p13), t (8; 9) (p11; q32), t (9; 22) (q34; q11) and inv (16) (p13 q22). In conclusion, cytogenetical detection is very important in differential diagnosis of clonal eosinophilic disorders and chronic eosinophilic leukemia, which is suggested to be done routinely in clinic.