Pathological Features, Treatment Options and Prognosis Assessment of Patients with Bone Lymphoma in Real-World / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma.@*METHODS@#The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively.@*RESULTS@#The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods.@*CONCLUSION@#Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.

Preliminary Study on the Characteristic of Plasma Cytokine Profiles in Patients with Idiopathic Multicentric Castleman Diseases / 中国实验血液学杂志

OBJECTIVE@#To investigate the characteristic changes of the plasma cytokine profile in Chinese patients with idiopathic multicentric Castleman diseases (iMCD).@*METHODS@#The plasma samples from 22 patients with confirmed diagnosis of iMCD were collected before treatments; Specimens from 17 patients with newly diagnosed multiple myeloma, 10 non Hodgkin's lymphoma, and 15 healthy donors were used as control. Seventeen kinds of cytokines were measured by cytokine beads array (CBA) and ELISA respectively.@*RESULTS@#Six cytokines were measured by ELISA. The concentrations of IL-2, IL-6, IL-21 and VEGF were significantly higher in the plasma of iMCD patients than those of the healthy donors (P＜0.01) and the level of IL-21 was highest in the iMCD group. There was no significant difference in the levels of IL-1β and IL-4 between the iMCD and healthy donor groups. Thirteen cytokines were measured by CBA assay, besides IL-6 level was confirmed to be higher in iMCD group than that in healthy controls (P＜0.01）, IL-12-p70 and IL-33 levels were also higher in iMCD group than those in control group (P＜0.05）, no significant difference of the rest cytokines was found between iMCD and the control group.@*CONCLUSION@#IL-6 and VEGF has shown to involved in the pathogenesis of iMCD, the results of preliminary study imply the role of IL-2 、IL-21、IL-12-p70 and IL-33 in this rare lymphoproliferative disease. Further studies are needed to elucidate the mechanism of these cytokines, which may shed some light on the identification of novel therapeutic targets against iMCD.

Incidence of Bone Marrow Involvement in Different Pathological Type Lymphoma Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the incidence of bone marrow involvement in patients with different pathological types of lymphoma.</p><p><b>METHODS</b>The results of bone marrow tests including bone marrow aspiration(BMA), flow cytometry detection, bone marrow biopsy(BMB) and F-FDG PET/CT, were analyzed retrospectively in 702 cases of newly diagnosed lymphoma with bone marrow assessment in our hospital from October 2000 to September 2016. If one of the above-mentioned 4 tests showed positive, the lymphoma patient was judged as bone marrow involved.</p><p><b>RESULTS</b>The incidence of bone marrow involvement (BMI ) in the patients with NHL was much higher than that in patients with HL [32.6 %(201/616) vs 15%(13/86)](P<0.05). For patients with NHL, the incidence of bone marrow involvement in B-cell lymphoma was higher than that in T-cell lymphoma (37.0% vs 22.6%)(P<0.05). According to different pathological types, the incidences of BMI in the patient with mantle cell lymphoma, hepatosplenic T-cell lymphoma, diffuse large B-cell lymphoma (DLBCL) and follical lymphoma (FL) were 88% (25/22), 100% (5/5), 21.8% (56/257), and 38.5% (15/39) , respectively.</p><p><b>CONCLUSION</b>The incidence of bone marrow involvement varies in different pathological types of lymphoma.Bone marrow assessment has significant importance for stading of newly diagnosed lymphoma patients.</p>

Salvage Trerapy for Patients with Relapsed and Refractory Lymphoma by Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To assess the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treating patients with relapsed and refractory lymphoma.</p><p><b>METHODS</b>Thirty-one consecutive patients with relapsed or refractory lymphoma received allo-HSCT. Used conditioning regimens included conditioning based on BEAM regimen(12 cases), conditioning based on modified Bu/Cy regimen(11 cases), conditioning based on Cy/TBI regemen(6 cases) and conditioning of Bu/Cy regimen(1 case). For provention of GVHD, the MMF was used on the basis of classcal protocol consisting of CsA combined with MTX. The infused HSC included the HLA-matched related HSC(11 cases), HLA nonidentical related HSC(13 cases) and HLA-matched unrelated HSC(6 cases). The bone marrow plus peripheral blood HSC were infused in 21 cases, while only peripheral blood HSC were infused in 9 cases. Among the 31 cases of relapse/refractory lymphoma, 18 patients were male and 13 were female, 4 cases were Hodgkin's lymphoma and 27 cases were non-Hodgkin's lymphoma. ALL of the 31 patients were qualified, as they were not in complete remission (CR) or in advanced stage at the time of transplantation.</p><p><b>RESULTS</b>Twenty-seven evaluable patients showed the engraftment of both neutrophil and platelet at a median of 12 days(range 10-20) and 13 days(range 9-34) respectively, 9 cases developed II-IV aGVHD, and cGVHD was observed in 3 patients, 5 patients can not achieve CR at 3 months after transplantation, and 6 patients relapsed after CR, the median follow-up of all the 31 patients after transplantation was 11.5 months (ranged, 0-141 months), and the 2-year OS was 46.1%±9.5% with median survival of 40 (9-141) months in the 15 survivors. The age (P<0.05), disease status before transplantation (P=0.020) and remission after transplantation(P=0.000) were significantly related with survival. Cox's proportional hazards regression model analysis showed that the age (P=0.041) and disease statue (P=0.020) before allo-HSCT were independent predictive factors for survival.</p><p><b>CONCLUSION</b>Allo-HSCT is an optimal treatment strategy for the patients with relapsed and refractory lymphoma who failed to most, if not all, available options.</p>

Values of Different Evaluation Criteria of InterimF-FDG PET/CT Scan for Prediction of Prognosis in Patients with DLBCL / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the prognostic value of interimF-FDG PET/CT (i-PET/CT) scan for the patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>A total of 70 cases of initially diagnosed of DLBCL by 158F-FDG PET/CT scans in our hospital were retrospectively analyzed. The 5-point scale, the Lugano classification and maximum standardized uptake value induction (ΔSUVmax) criteria were used respectively to assess i-PET/CT scans. Receiver-operating characteristics (ROC) analysis was used to determine an optimal cutoff for ΔSUVmax. Progression-free survival (PFS) and overall survival (OS) times were estimated as prognostic indicators using the Kaplan-Meier method and Cox regression.</p><p><b>RESULTS</b>Optimal cutoff to predict progression or death was 62% for ΔSUVmax. The positive predictive value (PPV) for 2-year PFS and OS of i-PET/CT diagnosed by 5-point scale was low, and could be improved by using the Lugano classification with decreased sensitivity or ΔSUVmax criteria. Kaplan-Meier survival curve analysis showed that the Lugano classification and ΔSUVmax were good predictors for PFS and OS, respectively, while the 5-point scale could only predict OS. Cox regression univariate analysis showed that the International Prognostic Index (IPI) score was better to predict PFS than 5-point scale, but worse than the three assessments in predicting OS. COX regression multivariate analysis showed that ΔSUVmax<62% was an independent risk factor of prognosis, while the Lugano classification was only the OS independent prognostic predictor.</p><p><b>CONCLUSION</b>Assessing i-PET/CT by 5-point scale is a limited value for predicting PFS and OS in DLBCL patients. The Lugano classification is recommended to discriminate the patients with poorer outcomes. The ΔSUVmax criteria for i-PET/CT of DLBCL patients is an independent prognostic predictor for PFS and OS, better than the IPI score.</p>

Clinical Features and Prognosis of 227 cases of Acute Myeloid Leukemia with Cross-lineage Antigen Expression / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyse the clinical features and prognostic significance of cross-lineage antigen expression in patients with acute myeloid leukemia(AML) in order to establish individualized treatment for a better outcome and prognosis.</p><p><b>METHODS</b>A total of 227 cases (exduding M3) were detected by flow cytometry for immune phenotype. The CD7(-)CD56(-)CD19(-) AML served as control. The clinical features, treatment response and prognosis of CD7(+) group, CD56(+) group and CD19(+) group were compared.</p><p><b>RESULTS</b>The detection rate of CD56(+),CD7(+) and CD19(+) in AML was 15.9%, 25.1% and 11.0%, respectively. There were no differences between CD56(+) AML, CD7(+) AML, CD19(+) AML, and CD56(-)CD7(-)CD19(-) AML in the proportion of blast cells, white blood cell count, hemoglobin level, platelet count and MDS transformed AML rate. The CR after the first course chemotherapy and cumulative CR in CD56(+) AML patients were lower than those in the control group (20.0% vs 58.1%, P=0.0099; 73.3% vs 87.5%, P=0.04). The median time of CR in CD56(+) AML was longer than that in the control group (118 days vs 46 days, P=0.04). The PFS time and OS time of CD56(+) AML were shorter than those in the control group (245 days vs 580 days, P=0.037; 494 days vs 809 days, P=0.04). The CR after the first course chemotherapy and cumulative CR in CD19(+) AML patients were higher than those in the control group(75.0% vs 58.1%, P=0.46; 100% vs 87.5%, P=0.02). The median time of CR in CD19(+) AML was shorter than that in the control group (28 days vs 46 days, P=0.02). The PFS time and OS time of CD19(+) AML tended to be longer than those in the control group (P=0.13, P=0.07, respectively). The median PFS and OS were not reached at the time of last follow-up. The CR after the first course chemotherapy, cumulative CR and median time to CR in CD7(+) AML patients were not different from those in the control group (53.1% vs 58.1%, P=0.67; 87.1% vs 87.5%, P=0.44; 50 days vs 46 days, P=0.44). No differences of PFS and OS were observed between CD7(+) AML and the control.</p><p><b>CONCLUSION</b>CD56(+) AML patients respond poorly to treatment, frequently relapse after complete remission and have a low survival rate. These patients need more intensive chemotherapy or in combination with other treatments. The interval of MRD detection should be shortened to find out relapse earlier. CD19(+) AML patients have a good treatment outcome and often accompanies with AML1/ETO fusion gene, which is known to be a good prognostic marker. Aberrant expression of CD7 on AML cells is not a poor prognostic factor in this study.</p>

Expression of CD56 and CD19 in Patients with Newly Diagnosed Multiple Myeloma and Their Relationship with Karyotypes and Prognosis / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the relationship between surface markers of CD56 and CD19 and karyotypes and prognosis in multiple myeloma.</p><p><b>METHODS</b>A total of 126 cases of newly diagnosed multiple myeloma in the first hospital of Peking university from 2011 to 2015 were enrolled in this study. Cytogenetic abnormalities and immunophenotypes were detected by using fluorescence in situ hybridization and flow cytometry respectively before chemotherapy. Bone marrow smear was used for detection of abnormal plasma cell infiltration. By combining with their basic data, the relationship between immunophenotypes, cytogenetics and prognosis of MM was analyzed.</p><p><b>RESULTS</b>(1) The median of myeloma cells in the 126 patients was 0.24（0.01-0.97）; the median of myeloma cells in 116 patients who have immunophenotype datas was 0.25（0.01-0.97）； the median of myeloma cells in CD19 positive patients was 0.11（0.01-0.53）; the median of myeloma cells in CD19 negative patients was 0.26（0.01-0.97）. The median of myeloma cells in CD19 positive patients was much lower than that in CD19 negative patients（P=0.036）. (2)In 116 patients detected by the immunophenotype, the myeloma cells expressed CD19,CD20,CD56 and CD117. Compared with CD56 negative patients(45/116,38.79%),CD56 positive patients(71/116,61.21%) had a clearly favorable disease outcome（OS was 53.0 month vs 31.0 month,P=0.016; PFS was 37.5 months vs 18.4 months, P=0.036）. (3)CD19 positive patients was 16.38%（19/116）,CD19 negative patients was 83.62%（97/116）； CD19 positive MM and CD19 negative MM had no difference in OS and PFS. (4)CD117 positive rate in CD19 positive patients was 42.11%(8/19), the CD117 positive rate in CD19 negative patients was 18.57%(18/97), the CD19 expression positively correlated with CD117 expression. (5)FISH detection was done for 67 newly diagnosed MM patients, 8 patients showed normal karyotypes(11.94%), 59 patients had abnormal karyotypes(88.06%). The most common abnormal karyotypes were IgH rearragement which occurred in 47 patients(70.15%). Other abnormal karyotypes included 1q21+, del(13q14),del(13q14.3),del(17p13) . These abnormal karyotypes occurred in 37 patients（55.22%）,31 patients（46.27%）,33 patients（49.25%） and 13 patients（19.40%） respectively. In comparison with CD19 negative MM patients, the incidence rate of 1q21+ and del(13q14.3) was significantly lower in CD19 positive patients(1q21+:33.33% vs 61.54%,P=0.016; del(13q14.3): 33.33% vs 53.85%,P=0.043）.</p><p><b>CONCLUSION</b>The prognosis of CD56 positive MM patients is better than that of CD56 negative MM patients, CD19 negative MM has more abnormal karyotypes and bone marrow infiltration,but they have no statistical prognostic differences.</p>

Clinical characteristics and long-term follow-up of 29 patients with primary mediastinal large B cell lymphoma / 中国实验血液学杂志

This study was aimed to investigate the clinical manifestation, pathological features, treatment and related prognosis factors of primary mediastinal large B cell lymphoma (PMLBCL). The clinical data of 29 PMLBCL patients admitted in Peking University First Hospital were summarized and the related factors were analyzed retrospectively from January 2000 to November 2013. The results showed that 29 patients with the median age 32 were all pathologically diagnosed as PMLBCL. The main clinical features included mediastinal bulk mass (72.4%), superior vena caval syndrome (51.7%), dyspnea (62.1%), serous membrane fluid (48.3%), with 62.1% extranodal invasion and 62.1% extra-thoracic involvement. According to Ann-Arbor stage, 16 patients (55.1%) were classified to stage I/II and 13 patients (44.9%) to stage III/IV, 12 patients (41.4%) had B symptoms. Among the 29 patients, 2 patients failed to be followed and the others were followed for the median time of 29 months, 17 patients achieved CR, 5 patients achieved PR, 1 patient replaced and 4 patients died of disease progression. The 5-year overall survival rate (OS) was 85.2%, in which RCHOEP regimen group patients had OS 94.4% and CHOEP group patients had OS 75%; 8 patients underwent auto-HSCT and 1 patients underwent allo-HSCT who kept in CR state. Univariate analysis by log-rank test showed albumin level and LDH ≥ 2ULN, the initial therapy response and IPI score were prognostic factors , but neither were independent prognostic factors by Cox Regression Model. It is concluded that PMLBCL has distinct clinical features. RCHOEP chemotherapy regimen can achieve satisfactory results, but needs to be explored by further clinical trials.

Clinical and pathological analysis of 236 patients with primary extranodal lymphoma / 中国实验血液学杂志

This study was aimed to analyze the clinical and pathological characteristics of patients with primary extranodal lymphoma (PENL). A total of 236 patients with PENL were enrolled to evaluate the clinical and pathological features. The clinical data of 236 patients with PENL confirmed by pathological and immunohistochemical methods between January 2001 and March 2012 were analyzed retrospectively. The results indicated that: (1)236 patients with PENL accounted for 40.7% of lymphoma over the same period. Median age was 55 years old (from 16 to 91 years old) . There were 153 males and 83 females(ratio 1.8: 1). (2)The common sites of involvement were gastrointestinal tract, nasal cavity, tonsil, mediastinum, skin, spleen, testis, bone and soft tissue, central nervous system, which accounted for 30.1% (71/236), 10.6% (25/236), 8.9% (21/236), 5.9% (14/236), 5.1% (12/236), 4.7% (11/236), 4.2% (10/236) , 4.2% (10/236) , 3.0% (7/236) respectively. (3)Symptoms of PENL did not have special characteristics, however its signs usually manifested with the enlargement or mass of organs, which accounted for 66.9% (158/236) in this study. (4)According to WHO classification of tumours of haematopoietic and lymphoid tissues in 2008, the common pathological type of gastrointestinal lymphoma was diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue lymphoma; the common pathological type of nasal lymphoma was extranodal NK/T cell lymphoma; the common pathological type of tonsillar lymphoma, testicular lymphoma, CNS lymphoma was diffuse large B-cell lymphoma. It is concluded that the primary extranodal lymphoma is not rare, it is alert to PENL while organs enlarge or mass forms, so that clinical physician should pay attention to tissue biopsy.

Prognostic implications of hematopoietic cell transplantation-specific comorbidity index on non-relapse mortality and overall survival after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the prognostic implications of hematopoietic cell transplantation-specific comorbidity index (HCT-CI) on non-relapse mortality (NRM) and overall survival (OS) in patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Clinical data of 161 cases received allo-HSCT from July 2003 to November 2010 were analyzed retrospectively. The prognostic significance of HCT-CI, age, sex, conditioning regimens, disease status before transplantation, graft source and the degree of HLA matches for NRM and OS was conducted by COX regression model. The prognostic impact of HCT-CI on NRM and OS was performed in all patients under different disease status before transplantation.</p><p><b>RESULTS</b>Of the 161 cases with allo-HSCT, 3-year NRM and OS were 26.4% and 61.4% respectively. NRM at 3 years in patients with HCT-CI score 0, 1-2 and ≥3 were 14.9%, 24.5% and 52.7% respectively. And OS at 3 years were 68.9%, 64.6% and 34.7% respectively. There were significant differences between HCT-CI score 0 and ≥3 groups for NRM and OS (P<0.01). High-risk disease status before transplantation (NRM: RR=3.35, P<0.01;OS: RR=3.53, P<0.01) and HCT-CI score≥3 (NRM: RR=6.85, P<0.01;OS: RR=3.77, P<0.01)were independent risk factors by COX regression model. In the subgroup analysis according to disease status, high score of HCT-CI was associated with poor OS (P<0.01) and high NRM (P<0.01) in patients with low-risk, but not in those with high-risk disease status.</p><p><b>CONCLUSION</b>HCT-CI score and disease status before transplantation are independent risk factors for patients received allo-HSCT. HCT-CI score have prognostic implication for NRM and OS in patients with low-risk disease status, but not in high-risk group.</p>

Differential regulation of CCR5 expression on T lymphocytes in healthy donors after mobilization with rhG-CSF and its correlation with aGVHD / 中国实验血液学杂志

This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. The expression of CCR5 on CD4(+) and CD8(+) T cells in the peripheral blood (PB) before and after mobilization were detected by using flow cytometry (FCM) respectively. According to the changes of CCR5 expression on CD4(+) and CD8(+) T cells, the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated (non-downregulated) groups, and the incidence of grades II to IV aGVHD in two groups were compared. The results showed that the mean value of CCR5 expression on CD4(+) and CD8(+) T cells in PB was not different significantly after mobilization (P > 0.05). Apparent inconsistency was showed among different individuals. Thirty-four (50%) donors displayed downregulation of CCR5 expression, while 34 (50%) donors manifested unchanged or upregulated CCR5 expression on CD4(+) T cells. CCR5 expression on CD8(+) T cells was downregulated in 42 (61.8%), unchanged or upregulated in 26 (38.3%) donors. The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4(+) T cells were 16.1% and 41.9% (P = 0.032), and recipients with CCR5 downregulation on CD8(+) T cells showed an increased tendency of developing aGVHD (37.8% vs 16.0%, P = 0.065). In conclusion, rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells, which might influence the migration of T cells in vivo, decrease T cell trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation.

Clinical and prognostic analysis of 101 cases of primary gastrointestinal non-Hodgkin's lymphoma / 中国实验血液学杂志

This study was purposed to analyze the clinical characteristics and prognostic factors in patients with primary gastrointestinal non-Hodgkin's lymphoma (PGI-NHL). The pathological data of 101 PGI-NHL patients admitted in our hospital in the past 15 years were analyzed retrospectively. The results showed that 101 patients with PGI-NHL accounted for 14.49% of NHL in the same period, there were 64 males, 37 females, the range of ages was from 18 to 87 years old, median age was 61 years old; in disease distribution, the stomach PGI-NHL accounted for 58.42%, intestine PGI-NHL accounted for 39.60%, multiple GI involvements (MGI) accounted for 1.98%; in pathological type, diffuse large B cell lymphoma (DLBCL) accounted for 66.34%, mucosa-associated lymphoid tissue (MALT) lymphoma accounted for 17.82%, mantle cell lymphoma (MCL) accounted for 3.96%, enteropathy-associated T cell lymphoma (EATL) accounted for 7.92%, extra-nodal nasal type NK/T cell lymphoma accounted for 1.98%, follicular lymphoma (FL) accounted for 0.99%, small lymphocyte lymphoma (SLL) accounted for 0.99%. Eighty-nine out of 101 patients were followed up (49 cases live, 40 cases dead), data of the 12 patients were lost; the median survival time was 29 months (1 - 173). The three-year OS and five-year OS were 58.4% and 52.6% respectively. Univariate analysis revealed that the factors affecting OS included sex (P = 0.004), lesion site (P = 0.002), tumor size (P = 0.011), clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma (P = 0.003), IPI score (P = 0.000), pathological cell phenotype (P = 0.001), and pathological type (P = 0.006), their differences were statistically significant (P < 0.05). Multivariate Cox regression analysis indicated that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score, pathological type were independent prognostic risk factors affecting OS. It is concluded that clinical Lugano staging for gastrointestinal non-Hodgkin's lymphoma, IPI score and pathological type are independent risk factors affecting OS.

Influence of donor activating or inhibitory KIR on prognosis of unmanipulated allogeneic hematopoietic stem cell transplantation / 中国实验血液学杂志

This study was purposed to investigate the role of NK-alloreactivity and donor-inhibiting or activating KIR gene in predicting prognosis under unmanipulated allogeneic blood and marrow transplantation. A modified polymerase chain reaction sequence specific primers (PCR-SSP) method was used to typing KIR and HLA genotype of donors and recipients. The relationship between donor activating or inhibitory KIR and recipient HLA genotypes on event free survival (EFS), cumulative incidence of malignant relapse and transplant-related mortality (TRM) were investigated retrospectively in 67 patients undergoing hematopoietic stem cell transplantation. The results showed that no effect of 'KIR/HLA mismatched' was detected on acute graft-versus-host disease (aGVHD) and relapse. The EFS of KIR/HLA mismatched group was lower, especially KIR2DL1/HLA-C2 mismatched group (44.8% vs 69.2%, P = 0.043). However, EFS was better for the presence of donor-activating KIR2DS2 (81.3% vs 52.6%, P = 0.052), and the relapse rate was significantly lower for the presence of this genotype (7.7% vs 34.2%, P = 0.05). EFS was worse in patients homozygous for group 1 HLA-C (C1) when donor carries the activating KIR2DS1 (KIR2DS1 positive/HLA-C2-negative group, P = 0.028), and the incidence of aGVHD in this group was significantly higher than that in any other groups (P = 0.028). In multivariate analysis, advanced disease stage, more than two donor-activating KIR, donor KIR2DS2-negative genotype were associated with an reduced disease-free survival (HR = 3.34, 2.19, 3.18;and P = 0.005, 0.053, 0.066). Donor KIR2DS2-negative genotype were also associated with an increased risk of relapse (HR = 6.72, 9.43; and P = 0.019, 0.047). And donor KIR2DS1 positive/recipient HLA-C2 negative group was the only risk factor of TRM (HR = 3.27, 95% CI 1.78 - 9.06, P = 0.023). It is concluded that missing ligand for the donor inhibitory KIR has weak effect on the outcome of unmanipulated HSCT. The activating KIR play an important role in the EFS, relapse and TRM after HSCT. Donor KIR2DS1-positive/recipient HLA-C2-negative group and donor KIR2DS1 gene negative predict poor prognosis. Analysis of KIR genotype and its ligand is important for the selection of best donor and prognostic evaluation in unmanipulated allogeneic HSCT.

Combination of rituximab with autologous peripheral blood stem cell transplantation for treatment of diffuse large B-cell lymphoma: a single-center experience / 中华血液学杂志

<p><b>OBJECTIVE</b>This study was aimed to investigate whether incorporation of rituximab into high-dose chemotherapy with autologous peripheral blood stem cell transplantation (auto-PBSCT)could improve the survival of patients with diffuse large B-cell lymphoma (DLBCL), and evaluate the safety of this regimen.</p><p><b>METHODS</b>Twenty-five patients (age, 17 - 61 yrs) with DLBCL were treated with a sequential chemotherapy for remission induction, intensive chemotherapy for mobilization of stem cells, and high-dose chemotherapy followed by auto-PBSCT. Among 25 patients, 22 cases were at IV Ann Arbor stage, 60% cases with B symptom, and 10 cases with intermediate-high risk and 2 cases with high risk when evaluated by International Prognostic Index (IPI). The high-dose chemotherapy included BEAM regimen for 21 patients, and TBI conditioning regimen for 4 patients. Each patient received infusion of rituximab at a dose of 375 mg/m(2) for 2 times, each at peripheral blood stem cell mobilization and peripheral stem cell infusion.</p><p><b>RESULTS</b>20 patients achieved complete remission (CR) before transplantation. After high-dose chemotherapy and auto-PBSCT, 92% patients achieved CR. At a median follow-up of 45 months, the estimated 3-year overall survival (OS) and progression-free survival (PFS) were 78.9% and 75.9%, respectively, for all patients; while those were 87.4% and 82.4% for patients achieved CR before auto-PBSCT. Multivariate analysis by Cox regression revealed that failure to achieving CR before auto-PBSCT was an independent prognostic factor affecting OS, while factor affecting PFS was IPI scores. Rituximab was generally well tolerated with few side-effects.</p><p><b>CONCLUSION</b>Our results suggested that the addition of rituximab to high-dose chemotherapy followed by auto-PBSCT was effective and safe for patients with DLBCL.</p>

Clinical investigation of primary amyloidosis with autologous hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the treatment of primary amyloidosis with high-dose melphalan and autologous hematopoietic stem cell transplantation to further examine the survival, hematologic response, and improvement of amyloid-related organ dysfunction.</p><p><b>METHODS</b>Retrospective analysis of 20 patients with primary amyloidosis treated with autologous hematopoietic stem cell transplantation. The status of major organ function before transplantation, mobilization programs and conditioning regimen as possible risk factors for survival were also investigated.</p><p><b>RESULTS</b>Of 20 cases, 11 out of 15 evaluable cases achieved hematologic response, among them, 6 got complete remission (CR, 40%) and 5 partial remission (PR, 33%). The median onset time was 3.0 months (1.5 - 4.0 months) and 4 months (3 - 5 months), respectively after transplantation. The overall hematologic response was 73%. The 11 hematologic responders also had kidney responses. The median time to achieve kidney response was 3 months (2 - 6 months). The 3-year overall survival of the cohort of cases was 71.4%. The major causes of death were heart failure, renal dysfunction and gastrointestinal bleeding. G-CSF alone could obtain satisfactory mobilization results and most of patients well tolerated to the conditioning regimen of melphalan doses from 140 mg/m(2) to 200 mg/m(2).</p><p><b>CONCLUSION</b>Treatment of primary amyloidosis with high-dose melphalan followed by autologous peripheral blood stem cell transplantation produced high efficacy. The cardiovascular system involvement, renal dysfunction and the abnormality of coagulation function before transplantation may be the risk factors for survival.</p>

Study on chronic health conditions and its related risk factors in recipients after hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the chronic health conditions (CHC) in long-term survival recipient after hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>The CHC of 101 cases survived for more than 1 year after HSCT were collected according to Bone Marrow Transplant Survivor Study (MBMTSS) questionnaire. The differences of the incidence and severity of CHC between auto-HSCT and allo-HSCT, HLA-matched and HLA-mismatched family donors HSCT were compared, and risk factors related to chronic health conditions were analyzed retrospectively in family donor HSCT.</p><p><b>RESULTS</b>Of the 101 HSCT survivors, 48.5% reported one or more chronic health conditions, and 83.7% of which were mild to moderate. The CHC in HLA-matched related donors HSCT were more serious than in HLA-mismatched related donors HSCT. The percentage of CHC total score above 3 in allo-HSCT recipients (32.1%) was higher than that in auto-HSCT ones (10.0%). The percentage of CHC total score 1-2, 3-4, and above 5 in HLA-matched family donors HSCT were 23.5%, 29.4%, and 14.7%, respectively, being significantly higher than those in HLA-mismatched ones (15.6%, 15.6%, and 6.2%, respectively). CHC was mainly related to chronic graft-versus-host disease (cGVHD). Single variable analysis showed that younger age at time of transplantation, HLA fully matched, the use of antithymocyte globulin (ATG) in the conditioning regimens were favorable for CHC. COX-regression Model showed that age was the only independent risk factor for predicting the CHC in family donor HSCT.</p><p><b>CONCLUSION</b>The chronic health conditions after HSCT is mild to moderate, these complications in HLA-matched related donor HSCT are more serious than those in HLA-mismatched related donor HSCT. The age at transplantation is the only independent risk factor for chronic health conditions.</p>

Hematopoietic reconstitution on the prognosis of hematological malignancies after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the impact of the time to hematopoietic reconstitution on the prognosis of hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>173 patients with hematological malignancies treated with allo-HSCT (excluding umbilical cord blood transplantation) at Peking University first Hospital between 2003 and 2011 were analyzed retrospectively. According to the median time to neutrophil and platelet engraftment, the patients were divided into tow groups. The 5-year overall survival (OS), transplant-related mortality (TRM), relapse rate (RR) and prognostic factors were analyzed.</p><p><b>RESULTS</b>The quicker neutrophil engraftment group with an estimated 5-year OS rate of 66.63%, 5-year TRM of 21.58% and 5-year RR of 18.65%. The slower neutrophil engraftment group with OS of 61.84%, TRM of 24.14% and RR of 23.57%. Univariate analysis demonstrated that no relationship was found between time to neutrophil engraftment and OS, TRM and RR (P = 0.462, P = 0.893, P = 0.545, respectively). There seems to be a trend toward increasing incidence of OS in quicker platelet engraftment group(OS were 69.44% and 54.31%, respectively), but no significant difference (P = 0.065). TRM were 19.13% and 25.45%, respectively (P = 0.424), RR were 17.36% and 24.71%, respectively (P = 0.251). Multivariate analyses showed that the time to neutrophil engraftment was not a significant risk factor for prognosis, the time to platelet engraftment was an independent risk factor for OS and TRM, but not a significant risk factor for RR. Pre-transplantation disease status was the only independent prognostic factor for RR.</p><p><b>CONCLUSIONS</b>The time to platelet engraftment was a significant predictor after allo-HSCT. Early platelet engraftment increased OS, which this may be due to decreasing TRM.</p>

Long-term outcomes in adults with leukemia treated with transplantation of two unrelated umbilical cord blood units / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Wide application of umbilical cord blood transplantation (UCBT) in adult patients is limited by low cell-dose available in one umbilical cord blood (UCB) unit. The aim of this study was to investigate the safety and long-term outcomes of UCBT from unrelated donors in adult and adolescent patients with leukemia.</p><p><b>METHODS</b>Thirteen patients with leukemia received double-unit UCBT with human leukocyte antigen (HLA) mismatched at 0 - 2 loci. We analyzed the engraftment, graft-versus-host disease (GVHD) and survival.</p><p><b>RESULTS</b>Twelve evaluable patients (92.3%) had neutrophil and platelet engraftment at a median of 21 days (range, 16-38 days) and 34 days (range, 25 - 51 days), respectively. At day 30, engraftment was derived from one donor in 8 patients (66.7%, 95%CI 40.0% - 93.4%), and from both donors in 4 patients (33.3%, 95%CI 6.7% - 60.0%) with 1 unit predominated. Unit with larger nucleated cell (NC) dose would predominate in engraftment (P = 0.039), whereas CD34(+) cell dose or HLA-match failed to demonstrate any relationship with unit predominance. Only one patient developed grade II acute graft-versus-host disease (aGVHD). Chronic GVHD (cGVHD) was observed in 2 of 11 patients who survived more than 100 days, and both were limited. The median follow-up after transplantation for the 13 patients was 45 months (range 1.5 - 121.0 months) and 72 months (range 41.0 - 121.0 months) for the 8 alive and with full donor chimerism. The 5-year cumulative disease free survival (DFS) was (61.5 ± 13.5)%. Of the 13 patients, 5 patients died in 1 year and 1-year transplantation related mortality (TRM) was 23.1% (95%CI 0.2% - 46.0%).</p><p><b>CONCLUSION</b>Double-unit UCBT from unrelated donors with HLA-mismatched at 0-2 loci may overcome the cell-dose barrier and be feasible for adults and adolescents with leukemia.</p>

Application of SPECT/PET in patients with lymphoma and its significance in monitoring relapse / 中国实验血液学杂志

The aim of this study was to evaluate the application value of SPECT/PET (18)F-FDG imaging in patients with lymphoma and its significance in monitoring relapse of this disease. A retrospective analysis of 71 SPECT/PET examinations was performed in patients with lymphoma diagnosed by pathologic and immunohistochemistry means from 1998 to 2008 in Peking university first hospital. The results showed that 28 patients underwent SPECT/PET before initial therapy, the accuracy of SPECT/PET and CT were 100% and 81.7% respectively. The diagnostic sensitivity of SPECT/PET and CT for foci were 85.7% and 53.5% respectively, and there was significant difference between them (p = 0.003). The diagnostic sensitivity of SPECT/PET and CT for extranodal foci were 91.3% and 56.5% respectively, there was significant difference also between them (p = 0.007). 32 patients underwent 43 SPECT/PET for monitoring relapse during follow up. The positive predictive value and negative predictive value of SPECT/PET for relapse were 100% and 92.9% respectively. The relapse were found by SPECT/PET in 6 patients more early than appearance of clinical symptoms and physical signs as well as laboratory examination, imaging examination. In conclusion, SPECT/PET has significant value in diagnosing and monitoring relapse for patients with lymphoma.

Quantitative monitoring of mononucleated cell Epstein-Barr virus (EBV)-DNA for predicting EBV associated lymphoproliferative disorders after stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To monitor blood cells EBV-DNA copies by quantitative Epstein-Barr virus (EBV) polymerase chain reaction after hematopoietic stem cell transplantation (HSCT) and to evaluate its implication.</p><p><b>METHODS</b>EBV-DNA copies of peripheral blood mononucleated cells (PBMNCs) were detected by fluorescence quantitative PCR once a week since conditioning regimen from fifty one patients received HSCT. Correlation between development of lymphoproliferative disorders (LPD) and EBV-DNA copies and influence factors of EBV reactivation were analyzed.</p><p><b>RESULTS</b>The cumulative incidence of EBV viremia was 58.8%. EBV reactivation occurred (39.6 +/- 23.5) days after HSCT, later than that of cytomegalovirus (CMV) reactivation (25.0 +/- 15.1) days (P < 0.01). HLA mismatch (P < 0.01), use of antithymocyte globulin (ATG) (P < 0.01), age less than twenty (P < 0.001) were factors for EBV reactivation, (93.3% vs 48.1%, 92.3% vs 18.7%, and 100% vs 53.1%, respectively). EBV related post-transplant lymphoproliferative disorders (EBV-PTLD) occurred only in 4 out of 30 (13.3%) EBV reactivation patients, whose EBV DNA load maintained over 10(6) copies/ml for at least two weeks (4 out of 13 cases). The median survival time of EBV-PTLD patients was 19.5 (11 - 75) days.</p><p><b>CONCLUSIONS</b>EBV reactivation occurs frequently after HSCT, especially in those received HLA mismatch grafts, used antithymocyte globulin or aged under twenty. Patients with EBV loads over 10(6) copies/ml, especially lasting over two weeks, appear to have an increased risk for PTLD, and pre-emptive therapy may be of clinical useful.</p>