In order to find an appropriate model suitable for a multistate survival experiment, 634 patients with chronic myeloid leukaemia (CML) were selected to illustrate the method of analysis. After transplantation, there were 4 possible situations for a patient: disease free, relapse but still alive, death before relapse, and death after relapse. The last 3 events were considered as treatment failure. The results showed that the risk of death before relapse was higher than that of the relapse, especially in the first year after transplantation with competing-risk method. The result of patients with relapse time less than 12 months was much poor by the Kaplan-Meier method. And the multistate survival models were developed, which were detailed and informative based on the analysis of competing risks and Kaplan-Meier analysis. With the multistate survival models, a further analysis on conditional probability was made for patients who were disease free and still alive at month 12 after transplantation. It was concluded that it was possible for an individual patient to predict the 4 possible probabilities at any time. Also the prognoses for relapse either death or not and death either before or after relapse may be given. Furthermore, the conditional probabilities for patients who were disease free and still alive in a given time after transplantation can be predicted.
Bone Marrow Transplantation ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*mortality ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/surgery ; Models, Statistical ; Probability ; Survival Analysis

Child ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; complications ; diagnosis ; Male ; Priapism ; etiology ; surgery

Adult ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; complications ; surgery ; Male ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; complications ; surgery

This study was aimed to detect the changes of bcr/able gene level in ph+ CML patients at different stages after allo-HSCT by real-time quantitative PCR and to evaluate the significance of this detection. The serial detection of bcr/abl fusion gene levels in 21 cases of CML treated with allo-HSCT was performed by RQ-PCR. The results showed that the bcr/able fusion gene could not be detected in 7 out 21 CML cases with positive fusion gene after allo-HSCT, while the bcr/abl fusion gene of different levels could be detected in 14 cases within 1-6 months. Dynamic detection indicated that the bcr/abl fusion gene levels in 9 cases were lower with relative value 0.0074%-0.088% and then could not be detected within 3-7 months after allo-HSCT. The bcr/abl fusion gene levels in 5 cases diagnosed as molecular relapse were between 0.077%-75%. The bcr/abl fusion gene levels in 1 out of 5 cases were 0.95%, 1.5%, and 0.16% in month 1, 2 and 3, respectively, and turned to negative in the month 4 without any treatment after allo-HSCT. 2 cases received the donor peripheral blood stem cell infusion, and then their bcr/abl mRNA levels could not be detected in bone marrow. Another 2 cases developed to the hematologic relapse, 1 out of 2 cases reached CR again after infusion of donor peripheral blood stem cells and chemotherapy, the other one died. It is concluded that serial quantifications of bcr/abl mRNA levels by RQ-PCR are reliable and can be used to detect the MRD, to monitor the outcome and to predict the relapse.
Adolescent ; Adult ; Female ; Fusion Proteins, bcr-abl ; genetics ; Genes, abl ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; surgery ; Male ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction ; Young Adult

OBJECTIVETo evaluate the treatment outcome of HLA-identical sibling allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) patients in first chronic phase (CP(1)).

METHODSFifty-one patients with CML-CP(1) received HLA-identical sibling allo-HSCT with conditioning regimens of TBI plus Cy or Bu plus Cy. Allogeneic peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) were performed for 28 and 23 patients, respectively. The median follow-up duration was 1434 (60 - 4062) days.

RESULTSFifty (98.0%) patients were successfully engrafted. Transplant-related mortality occurred in 8 (15.7%) patients. Acute graft-versus-host disease (aGVHD) occurred in 35 (68.6%) patients and 11 (21.6%) patients were grade II-IV, while chronic GVHD (cGVHD) did in 17 (37.8%) patients. Five (7.4%) patients relapsed. The 5-year probability of disease-free survival (DFS) was (79.2 +/- 6.4)%. There was no significant difference in 5-year DFS, death rate and treatment related syndromes between the two conditioning regimens (P > 0.05), and in 5-year DFS, relapse rate and death rate between two transplant choices (P > 0.05). However, the rate of relapse was lower in Bu/Cy group (P < 0.01) and the rate of cGVHD was higher in allo-PBSCT group (P < 0.05).

CONCLUSIONSAllo-HSCT can cure a significant proportion of patients with CML-CP(1). There was no significant difference in DFS between the two different conditioning regimens and between the different transplant choices. Donor lymphocyte infusion is a therapeutic alternative for CML patients relapsed after transplantation.

Adult ; Female ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; surgery ; Male ; Middle Aged ; Recurrence ; Siblings ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo evaluate the value of real time quantitative RT-PCR (Q-PCR) for monitoring bcr-abl mRNA levels in chronic myeloid leukemia (CML) patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSQuantification of bcr-abl mRNA was performed on 316 bone marrow samples from 112 patients with CML after HSCT by Q-PCR using the TaqMan probe system. The bcr-abl mRNA level was normalized by control gene abl. Cytogenetic response was evaluated with fluorescent in-situ hybridization (FISH).

RESULTSThe reproducible sensitivity of Q-PCR was 5 copies. The coefficients C(T) of interassay and intraassay variation for abl and bcr-abl were all below 2.0%. 289 bone marrow samples were collected from 101 CML patients who achieved a sustained complete cytogenetic response (CCyR) one month post allo-HSCT in a period of 6 - 60 months (median 12 months) at different intervals. In general, the median bcr-abl levels gradually decreased with the prolongation of time after HSCT: the median bcr-abl levels were 0.035% (0 - 0.406%) at 1 month post allo-HSCT (+ 1 month), 0.006% (0 - 0.683%) at +3 month, 0% (0 - 0.225%) at +6 month and remained 0% till +24 months. The highest level in CCyR patients detected at + 6 month was 0.068%. The bcr-abl mRNA level was decreased by 3 log in sustained CCyR patients at + 1 month compared with the newly diagnosed CML-CP patients (33.0%, data unpublished). On the contrary, Q-PCR results ranged from 0.12% to 13.45% in 8 cytogenetic non-responders or relapsed patients post allo-HSCT. Among them, 5 patients' samples were collected 1 - 2 months before cytogenetic relapse, the results were ranged from 0.09% to 3.42%. If 0.09% was assumed 0.09% as a threshold, 9 sustained CCyR patients (8.9%) were tested once higher than that within 6 month after HSCT but decreased to 0% eventually. 2 blast crisis patients achieved CCyR within 1.6 and 3 months after HSCT, but hematological relapse occurred after 1 and 1.5 months, and their bcr-abl mRNA levels increased dramatically from 0% and 0.14% to 46.9% and 75.9% respectively.

CONCLUSIONSQ- PCR is a sensitive, precise and reliable technique, and can be used to monitor CML patients post allo-HSCT regularly. Patients in blast phase of CML should be monitored more frequently.

Adolescent ; Adult ; Bone Marrow Cells ; metabolism ; Child ; Female ; Fusion Proteins, bcr-abl ; biosynthesis ; genetics ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; surgery ; Male ; Middle Aged ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods

OBJECTIVETo analyze the influence of HLA compatibility on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with chronic myeloid leukemia (CML).

METHODSThis retrospective study involved 121 CML patients including 90 in chronic phase, 8 in accelerated phase and 23 with blast crisis. Of these patients, 85 received related and 36 had unrelated donor allo-HSCT. The conditioning regimens included total body irradiation with cyclophosphamide in 37 patients, and modified BUCY protocol in 84 patients. Cyclosporine A (CsA) and methotrexate (MTX) were used for graft-versus-host disease (GVHD) prophylaxis in patients undergoing HLA-matched sibling donor transplants. CsA, MTX, antihuman thymocyte globulin and mycophenolate were used in all the patients undergoing HLA-mismatched related donor and unrelated donor transplants. The prognostic factors of CML were evaluated using Cox regression and the cumulative overall survival and the disease-free survival were estimated using Kaplan and Meier survival analysis model.

RESULTSThe incidence of II-IV acute GVHD was 26.1% in HLA-matched and 53.3% in HLA-mismatched cases (P=0.006), with a 5-year cumulative incidence of chronic GVHD of 47.4% and 49.6%, respectively (P=0.947). The 5-year cumulative incidences of disease relapse was 16.7% in the total patients, with a 5-year cumulative overall survival (OS) of 70.5% and disease-free survival (DFS) of 63.4%. The 5-year OS was 78.2% in HLA-matched cases, as compared with 47.6% in HLA-mismatched cases. Multivariate analysis with Cox regression model identified HLA mismatch, II-IV acute GVHD, and advanced phase as the risk factors affecting the OS.

CONCLUSIONHLA mismatch can significantly increase the incidence of II-IV acute GVHD following allo-HSCT and decrease the long-term survival rate, which is not related to the donor source.

Adolescent ; Adult ; Child ; Female ; HLA Antigens ; immunology ; Hematopoietic Stem Cell Transplantation ; methods ; Histocompatibility Testing ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; immunology ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Tissue Donors ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Young Adult

Blood Donors ; Child ; Cord Blood Stem Cell Transplantation ; adverse effects ; methods ; Female ; Follow-Up Studies ; Graft vs Host Disease ; prevention & control ; Humans ; Infant, Newborn ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; surgery ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo analyze the risk factors of allogeneic stem cell transplantation (allo-SCT) for chronic myeloid leukemia (CML) in an attempt to avoid transplant risks.

METHODSA total of 121 CML patients received allo-SCT were analyzed retrospectively. The risk analysis was based on the EBMT score (gratwohl score) which included donor type, age of patients, disease status before transplantation, donor/recipient sex match and time interval between diagnosis to allo-SCT. Patients were divided into 3 risk groups based on their EBMT score: low risk (score 0-2), intermediate risk (3-4) and high-risk (5).

RESULTSThe median follow-up duration was 37 (1 - 126) months. The estimated 5-year overall survival (5 y-OS), non-relapse mortality (5 y-NRM) and relapse rate (5 y-RR) were (56.8 ± 5.0)%, (35.6 ± 4.9)% and (12.9 ± 3.7)%, respectively. The 5y-OS, NRM and RR were (66.0 ± 6.1)%, (28.8 ± 6.0)% and (7.8 ± 3.3)% in the low risk group being significantly superior to both intermediate-risk \[(47.2 ± 8.7)%, (43.6 ± 8.5)% and (18.7 ± 8.1)%\] and high-risk group \[(16.8 ± 15.2)%, (66.7 ± 25.5)% and (50.0 ± 25.0)%\] (P = 0.0015, 0.045 and 0.0053 for OS, NRM and RR respectively).

CONCLUSIONThe EBMT risk score can effectively predict the overall outcome, relapse and transplant-related mortality of allo-SCT for CML patients.

Adolescent ; Adult ; Child ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; diagnosis ; surgery ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Risk Factors ; Tissue Donors ; Transplantation, Homologous ; Young Adult

OBJECTIVETo investigate the therapeutic efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with chronic myelogenous leukemia (CML), and to analyze the possible prognostic factors.

METHODSThe clinical data of 20 children with CML who had received allo-HSCT was analyzed retrospectively to investigate possible prognostic factors, including age, sex, interval between diagnosis and transplantation, HLA matching between donors and recipients, illness status on transplantation and acute and chronic graft-versus-host disease (GVHD).

RESULTSAt the end of follow-up, 13 of the 20 treated children had disease-free survival (DFS) and the rest (7 cases) died. Four died of severe acute GVHD, two of chronic GVHD and its complications, and one of relapse after transplantation. The three-year DFS was (64.6±1.1%). As shown by the univariate analysis, age was the most important prognostic factor in children with CML who had received allo-HSCT (P<0.05), and in children over 10 years, the prognosis was poor. No other of the above factors had a significant impact on prognosis (P>0.05). The multivariate logistic regression analysis also confirmed age as the only prognostic factor (P<0.01). Severe acute and/or chronic GVHD was the most important cause of patient death. 10/10 HLA-matched donors could improve the transplantation outcome.

CONCLUSIONSAllo-HSCT is an effective treatment for children with CML. To improve the prognosis and treatment outcome, children with CML aged over 10 years should receive allo-HSCT as early as possible. 10/10 HLA-matched donors are preferred in allo-HSCT and GVHD should be prevented.

Adolescent ; Child ; Child, Preschool ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Histocompatibility Testing ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; mortality ; surgery ; Logistic Models ; Male ; Retrospective Studies ; Transplantation, Homologous