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Objective:To evaluate risk factors and available treatments of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia.Methods:A total of 280 patients were retrospectively analyzed from January 2008 to December 2018 in Affiliated Cancer Hospital of Zhengzhou University. Clinical data were collected including disease patterns, pre-transplantation status, chromosome karyotype, conditioning regimen, types of donor, extramedullary disease before transplantation and graft-versus-host disease (GVHD). The log-rank test and Cox proportional hazard model were uesd for univariate analysis and multivariate analysis, respectively.Results:Twenty patients developed EMR (7.14%). The median time of EMR was 7.5 (1-123) months after allo-HSCT. The mortality of EMR was 80% (16/20). Univariate analysis identified disease patterns, second complete remission (CR2) or progressive disease before transplantation, extramedullary disease, abnormal karyotype and conditioning regimen without total body radiation as significant factors correlated to EMR ( P<0.05). Multi-variable analysis revealed that CR2 or progressive disease ( RR=3.468,95% CI 2.189-7.786), abnormal karyotype ( RR=1.494,95% CI 1.020-2.189) and extramedullary disease before transplantation ( RR=8.627,95% CI 3.921-18.452) were independent risk factors of EMR. Conclusions:The clinical outcome of EMR after allo-HSCT is poor.It is crucial to comprehensively assess and identify EMR as early as possible.
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To analyze the prognostic factors of extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute lymphoblastic leukemia (ALL).The clinical data of 33 relapsed patients in 95 ALL patients receiving allo-HSCT were analyzed retrospectively. The median time of relapse was 5.7 (0.7-52.3) months. Extramedullary relapse was recorded in 10 cases (10.5%), bone marrow relapse in 15 cases (15.8%), and both extramedullary and marrow relapse were seen in 8 cases (8.4%). The median time of EMR was 7.4(0.7-52.3) months. The most commonly involved organ was central nervous system, followed by testis and bone. The 3-year OS rate in EMR patients was (33.3±11.1) %. Univariate analysis showed that disease state before transplantation ( P=0.026), extramedullary infiltration before transplantation ( P=0.005), conditioning regimens ( P=0.033) and acute graft-versus-host disease(aGVHD) ( P=0.013) were significantly correlated with EMR. Multivariate analysis suggested that extramedullary infiltration ( RR=5.067, 95 %CI1.542-16.645, P=0.007) and aGVHD( RR=3.585, 95 %CI1.245-10.320, P=0.018) were independent predictive factors of EMR in ALL patients after allo-HSCT.
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Objective@#To investigate the characteristics and prognosis of clonal chromosomal abnormalities appearing in Philadelphia negative metaphases (CCA/Ph-) cells in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy.@*Methods@#The clinical data of 30 cases with CCA/Ph- during TKI treatment in Henan Cancer Hospital from August 2007 to July 2017 were retrospectively analyzed. The univariate factor was analyzed by Kaplan-Meier method. Multiple-factor was analyzed by Cox proportional risk model.@*Results@#Of the 30 cases, 19 (63.3%) were males. At the first detection of CCA/Ph- the median age was 44 (rang 14-68) years old and the median treatment of TKI was 13 (rang 2-94) months. The clones proportion of first detected CCA/Ph-≥ 50% was found in 18 (60.0%) cases. TKI treatment for 3 months with BCR-ABLIS less than 10% was seen in 14 (46.7%) patients. 63.3% (19/30) of CCA/Ph- was transient (only one time) and 36.7% (11/30) was repeated (≥2 times) . Trisomy 8 dominant accounted for 60.0% (18/30) , -7/7q- for 13.3% (4/30) , loss of chromosome Y 6.7%. With a median of follow-up 50 months, 76.7% (23/30) cases were in complete cytogenetic response (CCyR) ; 63.3% (19/30) in major molecular response (MMR) , 43.3% (13/30) in undetectable minimal residual disease (UMRD) . The median event-free survival rate of (EFS) were 44 months, and 2-year and 5-year EFS were (82.1±7.3) % and (52.4±12.8) %, respectively. The median overall survival (OS) were 50 months, and 2-year and 5-year OS rates were (92.6±5.0) % and (77.2±14.7) %, respectively. Univariate analysis shows that the 2-year EFS of who in males, more than 2 times CCA/Ph-, BCR-ABLIS>10% at 3 months after TKI were significantly lower than women, transient CCA/Ph-, and BCR-ABLIS≤10% (P<0.05) . The 2-year OS rate in whom the occurrence frequency of CCA/Ph- more than twice was significantly lower than those with transient CCA/Ph- (P<0.05) . Multivariate analysis showed that CCA/Ph- was an independent risk factor (RR=4.741, 95%CI 1.21-18.571, P=0.018) for EFS in CML patients.@*Conclusion@#Trisomy 8, -7/7q-, and -Y were the most common CCA/Ph- during TKI treatment, with high clones proportion of ≥50%. CCA/Ph- mainly occurred transiently or was permanent occasionally. CCA/Ph- recurrence (≥2 times) was an independent risk factor for EFS and OS in CML with TKI.
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Objective@#To investigate the influence of additional clonal chromosome abnormalities in Ph negative cells (CCA/Ph-) on the efficacy of chronic myeloid leukemia (CML) after tyrosine kinase inhibitors (TKI) treatment.@*Methods@#The clinical data of 28 CML patients with CCA/Ph- treated in Henan Cancer Hospital from July 2014 to December 2017 were analyzed retrospectively. The univariate analysis was carried out by Kaplan-Meier method. Multivariate analysis was done by Cox proportional risk model.@*Results@#A total of 28 CCA/Ph-patients were recruited including 17 males and 11 females with median age of 42.5 years old. The most common CCA/Ph-were trisomy 8 (60.7%), monosomy 7 (14.3%). 64.3% CCA/Ph-were transient and 35.7% recurrent (more than 2 times). Cytopenia in two or three lineages of peripheral blood was seen in 42.9% patients. As to the efficacy, 89.3% patients achieved major cytogenetic response (MCyR), 25% with major molecular response (MMR). The median follow-up time was 26.5 months. Treatment failure (TF) of TKI occurred in 32.1% patients with median duration of response 8 (1-41) months. Univariate analysis showed that TF rate was significantly correlated with the frequency of CCA/Ph-and cytopenia (all P<0.05). The MMR rate was also significantly correlated with cytopenia (P<0.05). Cytopenia of two lineages or pancytopenia was an independent risk factor related to MMR rate (RR=3.868, 95%CI 1.216-12.298, P=0.022) .@*Conclusions@#Cytopenia in CCA/Ph-appears to be an independent risk factor of MMR in CML patients with TKI treatment. The recurrent CCA/Ph-may link to higher treatment failure rate. Drug withdrawal or alternative strategy should be considered according to response and the ABL kinase mutations.
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Objective@#To observe the pregnancy outcome among patients with chronic myeloid leukemia (CML) treated with Nilotinib (NIL) .@*Methods@#Clinical data of pregnancy delivery in CML patients treated with NIL from March 2015 to January 2019 were retrospectively collected.@*Results@#A total of 11 patients were recruited with median pregnancy age 28 (25-40) years. The median duration of NIL treatment before pregnancy was 34 (3-48) months. There were 12 pregnancies, included 2 planned ones and 10 (83.3%) unplanned. In the 10 unplanned patients, 9 (90.0%) received NIL 600 mg/d. The median exposure time were 4 (4-7) weeks. In eight patients with delivery outcomes, 5 cases had well-developed babies, 2 had spontaneous abortion and 1 case with an baby of syndactyly deformity, whose mother was exposed to NIL 600 mg/d for 7 weeks in the early trimester of pregnancy. Seven infants were 4 boys and 3 girls with the median height at birth 50 (41-54) cm and median weight 3.2 (3.0-4.6) kg. They all grew with a normal pattern and well developed. Now the median age is 19 (4-41) months. The disease status during 12 pregnancies included 3 cases in CMR, 2 cases in MR4.0, 3 cases in MMR, 4 cases not acquiring MMR. The median time of drug discontinuation was 35 (15-36) weeks during pregnancy. No patient lost CHR during this period.@*Conclusions@#Female CML patients exposed to NIL 600 mg/d for 4 weeks in early pregnancy can give birth to normal babies, but there is still a risk of spontaneous abortion and congenital malformations.
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Objective To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemic children .Methods Clinical data of 54 leukemic children undergoing allo-HSCT were retrospectively analyzed from May 2006 to March 2018 .According to the source of donor ,they were divided into matched sibling donor allo-HSCT group (MSD ,n = 27 ) and unrelated donor group (URD ,n= 27) .The clinical outcomes of leukemic children receiving URD allo- HSCT were assessed and those in MSD allo-HSCT group were enrolled as control .Results One patient with refractory AML was not implanted in URD group and the remaining 53 cases were successful in hematopoietic reconstitution .The time of neutrophil and platelet ,the incidence of acute graft-versus-host disease (aGVHD ) , chronic GVHD (cGVHD ) , generalized cGVHD and their transplant-related complications including pulmonary complications ,hemorrhagic cystitis between two groups were not statistically different (P> 0 .05) .The incidence of serious aGVHD ,cytomegalovirus (CMV) and EB virus (EBV) infection was significantly higher in URD group than that in MSD group (P< 0 .05) .The proportion of non-recurrent deaths in URD and MSD groups was 80％ and 31 .3％ respectively and the difference between two groups was statistically significant ( P = 0 .041) .The 3- year disease-free survival rate (DFS) of URD group and MSD group was (52 .9 ± 9 .8 )％ ,(38 .5 ± 8 .7 )％ and the overall 3-year survival rate (OS) was (57 .9 ± 9 .5)％ and (46 .5 ± 9 .7)％ respectively . The inter-group difference was not statistically significant ( P > 0 .05 ) .Conclusions In leukemic children ,although the incidence of complications post URD allo-HSCT is significantly increased , the prognosis is comparable to MSD allo-HSCT .It is a good choice when there is no suitable sibling donor .
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Objective To observe regular monitoring in patients with chronic myeloid leukemia (CML) who received tyrosine kinase inhibitor (TKI), and to analyze its influencing factors. Methods A total of 857 patients with CML in Henan Tumor Hospital from October 2012 to October 2016 were collected. Patients were told to receive regular monitoring after receiving TKI treatment, including blood routine, bone marrow, BCR-ABL fusion gene and chromosomes. All patients were divided into good and poor compliance groups according to regular monitoring. Chi-square test was used to compare ABL kinase domain mutations rate and mortality between two groups. TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of transportation, annual income and gender were recorded respectively, and the factors affecting regular monitoring were analyzed by using single and multiple factor analysis. Results There were 390 and 467 patients in good and poor compliance groups respectively. Treatment failure rate was 19.49％ (76/390) and 25.91％ (121/467) in good and poor compliance groups respectively, the mutation rate was 28.95％ (22/76) and 7.44％ (9/121) respectively. The difference of ABL kinase domain mutation in patients with treatment failure of both groups was statistically significant (χ 2 =16.287, P < 0.01). The mortality was 0.77％ (3/390) in good compliance group, and 2.78％ (13/467) in poor compliance group, and the difference was statistically significant (χ 2 = 4.543, P = 0.033). The single factors analysis showed that TKI species, level of education, duration from diagnosis to treatment, teaching times, sites of follow-up, convenience of traffic and annual income were related with regular monitoring (all P < 0.05). Multiple-factor analysis showed that inconvenient transportation (β = 1.56, 95％ CI 1.74-3.74, P = 0.014), low education level (β = 1.67, 95％ CI 0.81-3.12, P = 0.041) and low income (β = 2.87, 95％ CI 1.31-4.51, 95％CI 1.74-3.74, P = 0.011) were independent factors for poor compliance in regular monitoring. In the result detection, 56 fusion genes fluctuated. Conclusions CML patients who received regular monitoring have a low treatment failure rate and mortality. Inconvenient transportation, low education level and low outcome are independent risk factors for regular monitoring. The single monitoring result can not prompt treatment effect, and thus it needs to review and monitor for many times.
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Objective@#To explore the occurrence, clinical characteristics, diagnosis and treatment of glomerulitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#Analysis were carried out based on the clinical data of 6 patients with de novo glomerulitis following allo-HSCT hospitalized in Henan Tumor Hospital from January 2008 to December 2016, and the clinical manifestation, pathology, diagnosis, treatment and outcome were investigated.@*Results@#The occurrence of glomerulitis was 1.26% (6/478). The median time was 447(272-1 495) d after allo-HSCT. Proteinuria and varying degrees of edema were present in all patients. Of the 6 patients, 4 patients with impaired renal function, 3 cases of hypertension, 5 cases of urine occult blood positive, 2 cases of hyperlipidemia. 5 patients underwent acute graft-versus-host disease (GVHD), 4 patients accompanied with chronic GVHD at diagnosis. Kidney pathology showed typical features of minimal change diseases in 1 patient, membranous nephropathy in 4 patients and mesangial proliferative glomerulonephritis in 1 case. Immunohistochemistry of glomerular lesions revealed that the immune complex deposition included IgG in 4 patients, C3 in 3 patients, IgM and C1q in 1 patient. Serum ANA was positive in 2 patients and serum IgG and IgM were in high level in 1 patient, respectively. Only 1 case was effective on glucocorticoid. 5 cases treated by low dose cyclophosphamide combined with mycophenolate mofetil (MMF), 2 cases achieved complete remission, and 3 cases were partial remission. Up to now, 2 cases died with lung infection, and 4 patients survived.@*Conclusion@#The predominant pathological type of glomerulitis was membranous nephropathy. Low-dose cyclophosphamide combined with MMF was an effective treatment.
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Objective@#To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh).@*Methods@#The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210.@*Results@#There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients. 3(9.4%) of the 32 vPh cases were simple variant translocations. Among the remaining 29 cases with complex variant translocations, 28 cases (87.5%) involved 3 chromosomes, and only 1 (3.1%) involved 4 chromosomes. Except for 8, 15, 18, X, and Y chromosomes, the other chromosomes were involved. The frequency of chromosome 12q(15.5%) and 1p (12.1%) were higher involved. The most common FISH signal pattern was 2G2R1Y (74.1%), followed by 1G1R2F (14.8%), 2G1R1Y (3.7%), 1G2R1Y (3.7%), 1G1R1Y (3.7%). The comparison of complete cytogenetic response (CCyR) (P=0.269), major molecular response (MMR) (P=0.391) were carried out between simple and complex mechanisms, without difference. Compared with the classic Ph, the patients with vPh had higher IM primary resistance rate (χ2=3.978, P=0.046), especially primary hematological resistance (χ2=7.870, P=0.005), but the difference of CCyR (χ2=0.192, P=0.661), MMR (χ2=0.822, P=0.365), EFS (χ2=0.509, P=0.476), OS (χ2=3.485, P=0.062) were not statistically significant, and multivariate analysis showed that the presence of vPh did not affect OS (RR=0.692, 95%CI 0.393-1.765, P=0.658)、EFS (RR=0.893, 95%CI 0.347-2.132, P=0.126) and PFS (RR=1.176, 95%CI 0.643-2.682, P=0.703).@*Conclusion@#CML-CP patients with vPh and classic Ph had similar demographic and hematological characteristics. Except for 22q11, 9q34, the frequency of chromosome 12q and 1p were higher involved. The most common FISH signal pattern was 2G2R1Y, and different mechanisms had no impact on TKIs therapy. Compared with cases with classic Ph chromosomes, the patients with vPh chromosomes had higher risk of IM primary resistance, especially primary hematological resistance, which can obtain deeper molecular response quickly after changing to second-generation TKIs and didn’t affect long-term outcomes and OS.
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Objective@#To explore the pregnancy outcome and disease status among patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitor (TKI) when they stopped TKI treatment during pregnancy.@*Methods@#The clinical characteristics, reproductive outcomes and disease status of the patients who stopped TKI due to pregnancy between November 2004 to November 2017 were retrospectively collected.@*Results@#A total of 14 CML patients in chronic phase (CML-CP), 12 patients were Sokal-low-risk. The median time of TKI treatment was 46.5 (15-123) months before the drug was stopped. The median age at the time of pregnancy was 29 (24-32) years. The median time of TKI exposure was 4 (0-9) weeks in 12 accidental pregnancies. Outcomes were available for 13 pregnancies, 9 cases (69.2%) delivered healthy babies, 1 case (7.7%) delivered polydactylia malformation baby, 3 cases (23.1%) had spontaneous abortion. The last one was still in pregnancy (no organ malformations were observed in color Doppler ultrasound). At the end of the follow up date, 10 children developed normal, the median age was 14 (0.7-65) months. Of the 14 patients who stopped TKI, 7 in complete molecular response (CMR), 3 in MR4 (BCR-ABLIS <0.01%, ABL transcript >10 000), 2 in major molecular response (MMR), 2 in complete cytogenetic response (CCyR). The median time of TKI discontinuation during pregnancy was 33.5 (4-40) weeks. At the end of pregnancy, 4 cases were in CMR, 4 in MR4, 1 in MMR and 4 in CCyR. No patients lost CCyR and complete hematologic remission.@*Conclusions@#During the treatment of imatinib and Nilotinib, unplanned pregnancy may have a normal infant, but may lead to spontaneous abortion and congenital malformations. Female of CML-CP who had sustained and stable MMR at least 24 months and Sokal-low-risk had higher safety factor discontinued TKI during pregnancy, but still had a risk of increasing tumor load, so monitored the level of BCR-ABL of peripheral blood monthly during pregnancy is necessary.
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To explore the efficacy and influencing factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid leukemia and granulocytic sarcoma (GS).Clinical outcome including hematopoietic reconstitution,transplant-related complications,survival and relapse were collected and retrospectively analyzed in 9 patients with myeloid leukemia and GS after allo-HSCT.Hematopoiesis reconstitution was achieved in all the 9 recipients.Four cases developed acute graft-versus-host disease (GVHD),and 1 with chronic GVHD.The median follow-up time after transplantation was 10(4-81) months.Only 2 cases survived,the other 7 died of relapse.The median time of relapse after transplantation was 5(3-19) months.Allo-HSCT is relatively effective treatment for patients with myeloid leukemia and GS.Relapse after transplantation remains the major factor of mortality.
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Objective To assess the effectiveness of unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of severe aplastic anemia (SAA),and the difference between URD allo-HSCT and matched sibling donor (MSD) allo-HSCT.Methods According to the source of donors,the SAA patients subject to allo-HSCT were divided into MSD allo-HSCT group (MSD group) and URD allo-HSCT group (URD group) from October 2001 to December 2016 in Henan Cancer Hospital.The efficacy and transplantation related complications were compared between two groups.Results There were no statistically significant differences in hematopoietic reconstitution and graft rejection between two groups.The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD was higher in the URD group than in the MSD group (30.76％ vs.8.57％,P =0.026;26.92％ vs.5.71％,P =0.021).However,other transplant-related complications including pulmonary complications and hemorrhagic cystitis,incidence of EBV and CMV reactivation and venous occlusive disease showed no significant difference between two groups.The estimated 5-year over survival was (73.6 ± 8.7) ％ in the MSD group and (72.7 ± 9.5) ％ in the URD group (P =0.878).There was no significant difference in 5-year disease-free survival between two groups (73.6 ± 8.7％ vs.70.3 ± 10.2,P =0.668).Conclusion URD-HSCT is a novel treatment approach and could be considered as first-line therapy in selected patients without MSD.
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Objective To explore the effective treatment with regimen of remission induction for relapsed/refractory precursor lymphocytic leukemia/lymphoma patients. Methods 6 patients with relapsed/refractory precursor lymphocytic leukemia/lymphoma including 2 acute lymphocytic leukemia, 4 lymphoblast lymphoma and 1 hybrid acute leukemia were treated by combination of CAG regimen with L-asparaginase (L-Asp) and prednisone (PDN). Results All patients responded to the regimen, in which 6/7 (85.7 %)patients achieved complete remission and 1/7 (14.3 %) patient achieved partial remission after one course.Light adverse events coursed by the regimen could be tolerated. Conclusion The regimen consisting of CAG, PDN and L-Asp is worth exploring for relapsed/refractory precursor lymphocytic leukemia/lymphoma.
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ObjectiveTo investigate the clinical characteristics in ABO-incompatible allogeneic peripheral blood stem cell transplantation(allo-PBSCT).Methods137 patients'clinical courses who accepted allo-PBSCT were retrospectively reviewed. Sixty-five cases of them were ABO-incompatible allo-PBSCT patients,including 32 ABO major mismatched cases,23 ABO minor mismatched cases and 10 ABO major and minor mismatched cases.Seventy-two ABO-identical cases were taken as control group.ResultsCompared with ABO-idential cases,the time of erythrocyte recovery after allo-PBSCT in ABO major and minor mismatched group was delayed [(73.2+10.3) d vs (97.5+10.4) d] (P ＜0.05).In ABO-incompatible group, the time of blood type switching in different ABO-incompatible types were found no significant difference (P ＞0.05) [ABO major mismatched:(45.7±17.3) d,ABO minor mismatched:(41.2+16.1) d and ABO major and minor mismatched:(48.4±20.9) d (P ＞ 0.05)].There were 8 cases who have a delayed time of blood type changing, including 6 cases demonstrated recipient-derived anti-A antibody. ConclusionABO-incompatible has no negative effect on allo-PBSCT.The time of erythrocyte reconstitution was delayed in ABO major and minor mismatched group.A delayed time of blood type switching tends to occur in ABO minor incompatible cases and patients who have anti-A antibody initially.
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Objective To explore the efficacy and safety of moderate-dose of etoposide (VP16) with granulocyte-colony-stimulating factor (G-CSF) for mobilization of peripheral blood stem/progenitor cells.Methods VP16 at 1.2 g/m2 was injected intravenously by six divided doses via a central vein, 2 times every 12 hours for 3 days in 31 patients with malignant lymphoma (30 non-Hodgkin lymphoma and 1 Hodgkin lymphoma). All patients received G-CSF 5 μg/kg were given twice daily subcutaneously from the day of the nadir of white blood cell (WBC) till the day before the last APBSC harvest. Results The mean time for the collection of stem cell was 12 days (10-15) following etoposide chemotherapy. The mean number of mononuclear cell (MNC) and CD+34 cells in collection were 7.8×108/kg (5.2-11.3×108) and 7.2×106/kg (5.3-13.1×106). respectively. 18 patients completed collection with a single apheresis, and 13 patients underwenttwice. All patients were recovered for haematopoiesis in following APBSCT. Median (range) time for the recovery of absolute neutrophil count (ANC)＞0.5×109/L and platelet＞20×109/L were+12 (+9-+18) days and +14 (+10-+21) days respectively. Slight adverse events coursed by the regimen could be tolerated. Conclusion VP16 at moderate dose with G-CSF is an effective and safe mobilizing regimen for autologous peripheral blood stem/progenitor cells in patients with malignant lymphoma. It was suggested to use extensively.