[Clinical and laboratory features of T-cell prolymphocytic leukemia in China].

OBJECTIVE: To investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL). METHODS: Eleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed. RESULTS: Of the 11 patients, nine were males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. The incidence of hyperleukocytosis (1/11) was less frequent than that in the British series (75%) (P=0.000). Lymphocyte counts in peripheral blood were increased in 9 of the 11 patients with the median absolute lymphocyte count (ALC) of 17.22(0.58-148.83)×109/L. Superficial lymphadenopathy and splenomegaly were the most common physical signs. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin(ß2-MG)were higher than normal level. All cases were positive for CD2/CD3/CD5/TCRαß, negative for CD1a /HLA-DR and TdT, and most of them were strong positive for CD7 expression. By chromosome analyses, most cases. (9/10) have normal chromosome. This rate is significantly higher than that of the British and American series (3% and 25%, respectively) (P=0.000, P=0.001). The 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any of our cases. With a median follow-up of 23.0 months, three patients died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50%, respectively. There were 3 patients with PFS over a number of years, whether it should be considered as the T-chronic lymphocytic leukemia (T-CLL) is worthy of further studies. CONCLUSION: The common clinical manifestations of T-PLL patients were increased lymphocyte counts and lymphadenopathy as well as splenomegaly. And most cases have high level of blood LDH and ß2- MG and normal chromosome karyotype.

[Outcomes of younger than 60 years old adults with Ph/BCR-ABL positive acute lymphoblastic leukemia: a single center clinical trial of BDH ALL 2000/02].

OBJECTIVE: To explore the treatment options for younger than 60 years old adults with Ph /BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL). METHODS: From January 2001 to June 2012, 42 adult patients were enrolled in the study. All patients received standard VDCP±L ±imatinb (IM) as induction therapy followed by intensive consolidation of modified Hyper-CVAD/MA±IM. At complete remission 1 (CR1), patients with appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT), the others sequentially received intensive consolidation ±IM and autologous HSCT (ASCT) at molecular CR (MCR), then MM±VP±IM as maintenance therapy. Overall survival (OS), disease free survival (DFS) and relapse rate (RR) were analyzed. RESULTS: CR rate after 1 cycle of induction chemotherapy was 83.3%. 39(92.9%) patients achieved CR. The median DFS and OS were (22.0±3.5) and (37.0±5.3) months respectively, with cumulative RR of (43.7±9.7)% during a median follow-up of 26.5(8-75) months. All 7 patients in CT group relapsed. Two patients received IM pre- and post-ASCT maintained MCR for 35 and 12 months after ASCT. But the other 3 ASCT recipients without IM died of relapse within 1 year. The transplant-related mortality rate in allo-HSCT group was 12.5%. The estimated 3-year OS in allo-HSCT (n=16), ASCT (n=5) and CT (n=7) groups were (66.7±12.2)%, (25.0±21.7)% and (16.7±15.2)%, respectively (P=0.014); meanwhile, the estimated 3-year DFS in those groups were of (56.3±12.4)%, (26.7±22.6)% and 0, respectively (P=0.002). CONCLUSION: IM combined with intensive chemotherapy significantly increased the CR rate with the improved quality of CR, which highlighted the feasibility of SCT. Allo-HSCT could decrease relapse to produce favorable OS and DFS in CR1 of young adults with Ph⁺ ALL. ASCT combined IM might be the treatment of choice for those achieved MCR but without donors.

[Clinical efficacy and safety of chemoimmunotherapy with rituximab,fludarabine and cyclophosphamide for chronic lymphocytic leukemia].

OBJECTIVE: To evaluate the efficacy and safety of a chemoimmunotherapy regimen of rituximab, fludarabine and cyclophosphamide (FCR) for patients with chronic lymphocytic leukemia(CLL). METHODS: The clinical data of 26 CLL patients receiving FCR regimen in our hospital from April 2003 to January 2012 were analyzed retrospectively. Patients were grouped according to indicators including Rai risk stratification, ß(2)-MG, LDH, ZAP-70, CD38, cytogenetics and immunoglobulin heavy chain variable region gene (IgVH) mutation status. Therapy efficacy and survival were evaluated and the safety of FCR regimen was assessed. RESULTS: Among 26 patients, the overall response rate ( ORR ) was 76.9%, 10 patients (38.5%) achieved complete remission(CR) and 10(38.5%) partial remission(PR). With a median follow-up time of 30 ( 3-98 ) months, the median estimated progression-free survival(PFS) for all patients was 42(16-68) months and median overall survival(OS) was 63(41-85)months. Clinical parameters associated with higher CR rates were ＜2 courses of prior treatment regimens, proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR, low LDH, low ß(2)-MG and ZAP-70 negative (P = 0.014, 0.008, 0.027, 0.035 and 0.013, retrospectively). PFS and OS time in minimal residual disease(MRD)-negative, normal LDH and proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR patients were significantly better than that of the control group (P＜0.05), PFS in the non-high-risk genetics group was significantly better than that in the high-risk genetics group (P = 0.005), while OS between two groups showed no statistically significant difference. The most common toxicities were gastrointestinal reactions (88.5%), followed by bone marrow suppression (80.8%): including neutropenia, anemia and thrombocytopenia. Infections accounted for 30.8%, mainly lung infection. CONCLUSION: FCR is an effective and well-tolerated therapy for patients with CLL. Patients with MRD-positive, elevated LDH, proportions of bone marrow lymphocytes declining＜50% after 2 courses of FCR and high risk genetics patients are suitable for more effective treatment after achieving treatment response.

[Analysis of the efficacy and prognosis on first-line autologous hematopoietic stem cell transplantation of patients with multiple myeloma].

OBJECTIVE: To explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed patients with multiple myeloma(MM). METHODS: From January 2005 to December 31, 2012, 60 patients with MM were enrolled. All patients received thalidomide or/and bortezomib-based induction therapy, then received high-dose melphalan (200 mg/m²) and autologous stem cell support to get a ≥ partial response (PR), and followed by thalidomide-dexamethasone (TD) ±bortezomib as consolidation or maintenance treatment. With the follow up to December 31, 2012, the overall survival (OS), progression free survival (PFS) and the prognostic factors, including ISS stage, response and fluorescent in situ hybridization (FISH) data of cytogenetics were analyzed. RESULTS: With a median follow up of 36.8 (12.0-102.5) months, the median OS and PFS estimate were not reached and 86.5 months, respectively. After transplantation, all (100%) patients received very good partial response (VGPR), and 34 (56.7%) patients achieved complete response (CR) after consolidation or maintenance treatment. The patients that achieved CR resulted in long term PFS (P=0.030), with no difference in OS (P=0.942). The univariate analysis showed that the abnormalities, including 13q14 deletion, 1q21 gain, IgH location and p53 deletion had the prognostic impacts. If the t(4;14) or p53 deletion was excluded, there would be no correlation between 13q14 deletion or 1q21 gain with PFS and OS. The patients with p53 deletion had a worst survival. CONCLUSION: There has been significant improvement in the outcome for young MM patients by using ASCT and novel drugs. Cytogenetic abnormalities and response to therapy are the main factors affecting the survival of patients.

[A preliminary study on the culture of single hematopoietic stem cell].

OBJECTIVE: To investigate the biological behavior including survival and proliferation of CD34 + CD38--Lin--cells when they are cultured at single cell level. METHODS: Purified umbilical cord blood CD34 + CD38--Lin--cells were separated at single cell level in 96-well plates using flow cytometry for four groups: control group (CD34 + CD38--Lin--cell plus stem cell medium) , Shh group (CD34 + CD38--Lin--cell plus stem cell medium and Shh), BMP-4 group (CD34 + CD38--Lin--cell plus stem cell medium and BMP-4), Jagged-1 group (CD34 + CD38--Lin--cell plus stem cell medium and Jagged-1). Methylcellulose medium was used in the colony-forming experiment which was also in four groups as previously. The number of cells and colony-forming units in each well for the four groups was evaluated at different time points (day 1, 3, 7) with fluorescence microscopy counting method. RESULTS: Division of single cell was observed to be amplified in all of these groups from day 3. And meanwhile, after 1-week culture, the survival rates for the treated groups were all higher than the control group (Jagged-1 group > BMP-4 group > Shh group > control), while the cell number in each well was also highest in the Jagged-1 group (Jagged-1 group > BMP-4 group > control). The number of wells with a cell number of zero was significantly fewer in all treated groups (especially the Jagged-1 group) than in the control group; meanwhile, the number of wells with a cell number higher than 17 was evidently higher in all the treated groups (especially the BMP-4 group) more than controls. Colony-forming units for erythroid (BFU-E), granulocyte (CFU-G), macrophage (CFU-M), and granulocyte macrophage (CFU-GM) were observed for all of these experimental groups, and there was no significant difference between the four experimental groups. CONCLUSIONS: CD34 + CD38 - Lin - cell can achieve the survival, self-renewal and proliferation when cultured at single cell level, and the adding of Shh, BMP-4, and Jagged-1 can enhance such capabilities. However, CD34 + CD38 - Lin - cell can only maintain cell totipotency in its niche.

[Analysis of clinical and laboratory characteristics and survival with hairy cell leukemia].

OBJECTIVE: To explore the clinical and laboratory characteristics and survival of Chinese patients with hairy cell leukemia (HCL). METHODS: A total of 30 HCL patients from August 1990 to March 2012 were retrospectively analyzed. RESULTS: There were 22 cases with classical HCL (HCL-C) and 8 with variant HCL (HCL-V). Splenomegaly was the most common physical finding. Leukocytosis was found in all cases of HCL-V. But pancytopenia only accounted for 36.4% (8/22) in HCL-C. And 3/5 of HCL-V had abnormal chromosome karyotypes. Ribosomal-lamellae complexes (RLC) were found only in about 3/12 of HCL cases. Chemotherapy regimens including purine nucleoside analogues achieved a better complete remission (CR) rate than other regimens (3/4 vs 1/18, P = 0.012) in HCL-C. The median follow-up period was 27 (1 - 142) months. There was no follow-up loss. Eleven cases progressed and 6 died. The median overall survival (OS) was not reached. And the 1, 3, 6-year OS rates were 84%, 78% and 58% respectively. The median progression-free survival (PFS) was (63 ± 24) months and the 1, 2, 5-year PFS rates were 86%, 72% and 44% respectively. The median PFS of HCL-V was significant shorter than HCL-C ((23 ± 3) vs (78 ± 12) months, P = 0.014). In HCL-C group, fever (P = 0.038) and anemia (P = 0.000) at diagnosis were poor prognostic factors. But purine nucleoside analogues made no significant difference in PFS. CONCLUSIONS: Pancytopenia is infrequent in Chinese HCL patients. And classical RLC is rare under electron microscope. Purine nucleoside analogues may achieve a better CR rate, but fail to improve PFS rate. As compared with HCL-C, HCL-V is common with genetic abnormalities and has a worse prognosis with a shorter PFS.

[Richter syndrome: clinical characteristics and treatment experiences].

OBJECTIVE: To summarize the clinical characteristics of Richter syndrome and explore the methods of successful treatment and timely diagnosis. METHODS: Five patients with Richter syndrome in the last three years (from January 2009 to December 2011) were analyzed retrospectively at our hospital, including their clinical features and therapy before and after transformation. RESULTS: There were 4 males and 1 female with a median age on a diagnosis of chronic lymphocytic leukemia (CLL) at 47 (44 - 68) years. The median duration from a diagnosis of CLL to transformation was 52 (5 - 90) months. As for cytogenetic abnormalities, 3/4 patients had 17p deletion by fluorescence in situ hybridization (FISH). The clinical manifestations on transformation included regional enlargement of lymph node (n = 2) and systemic enlargement of lymph nodes (n = 3). All diagnoses were confirmed by lymph node biopsy and all transformed into diffuse large B cell lymphoma (classical transformation). The subgroups were germinal center B-cell like (GCB) (n = 3) and non-GCB (n = 1). After transformation, one patient underwent sibling allo-stem cell transplantation and survived 24 months until April 2012. Another patient with auto-stem cell transplantation relapsed and died 12 months later. One patient lost the treatment opportunity due to worsening condition. Another 2 patients gained partial remission after therapy and survived 20 and 8 months respectively. CONCLUSIONS: Richter syndrome may occur during a late stage of CLL. Such a high-risk cytogenetic abnormality as del17p may be correlated with transformation. Early identification and optimal therapy may extend the survival of Richter syndrome. Allo-stem cell transplantation remains a curable option.

[Expression and prognostic significance of TOSO in CD19+ B cells from Chinese CLL patients].

OBJECTIVE: To investigate the expression and its prognostic significance of TOSO in CD19(+) B cells from Chinese chronic lymphocytic leukemia (CLL) patients. METHODS: The expression of TOSO was detected by absolute quantitative reverse transcription-polymerase chain reaction (RT-PCR) in a cohort of 85 untreated CLL patients from March 2006 to September 2010. Their status of immunoglobulin heavy chain variable (IGVH) somatic mutation, ZAP70 and CD38 were analyzed. RESULTS: The expression of TOSO was significantly elevated in CLL patients versus the healthy population (8.30 ± 2.99 vs 6.63 ± 1.22, P = 0.036) and other B cell lymphoproliferative diseases (8.30 ± 2.99 vs 7.12 ± 1.13, P = 0.023). The expression of TOSO was elevated in the IGVH non-mutated group versus the mutated group (9.87 ± 1.08 vs 7.61 ± 3.03, P = 0.000). The expression of TOSO was significantly elevated in Binet stage C patients versus in Binet stage B and Binet stage A patients (9.91 ± 3.03 vs 8.73 ± 1.86 vs 7.27 ± 2.83, P = 0.000). The expression of TOSO rose to (9.37 ± 2.12) in the chemotherapy group. And it was significantly higher than that in the observation group (7.19 ± 3.23, P = 0.001). At the cut-off point of 55 years old, the younger patients had a higher expression of TOSO than the elders (9.10 ± 2.06 vs 7.95 ± 3.22, P = 0.049). The expression of TOSO in ZAP70 and CD38-positive groups had no difference with those in the negative groups. CONCLUSION: The over-expressed TOSO in CLL cells is associated with a progressive disease. It may be an important prognostic factor for CLL.

[The significances of 13q14 deletion for development and prognosis of multiple myeloma].

OBJECTIVE: To determine the incidence and clinical significance of chromosome 13q14 deletion in multiple myeloma (MM). METHODS: Bone marrow samples were collected from 132 newly diagnosed MM patients referred to our hospital. Interphase fluorescence in situ hybridization (i-FISH) combined with magnetic activated cell sorting (MACS) were performed on chromosome 13q14 (RB-1). RESULTS: (1) i-FISH was used to investigate CD138-enriched bone marrow MM cells and revealed a 13q14 deletion rate of 51.5% (68/132), while conventional cytogenetic (CC) analysis revealed 13q deletions/monosomy 13 (Δ13) only of 5.0%(6/120). (2) Univariate analysis showed that 13q14 deletion rate by i-FISH > 25%, bone marrow plasma cells > 50%, ISS stage and ß(2)-MG ≥ 5.5 mg/L were associated with shorter overall survival (OS). Multivariate analysis revealed that 13q14 deletion rate by i-FISH > 25% was an independent unfavorable factor (P = 0.042). (3) Patients treated with bortezomib had a much better response than those treated with traditional chemotherapy (P = 0.001). There was no significant difference in OS between patients received bortezomib with and without 13q14 deletion (P > 0.05), indicating that bortezomib could reverse the poor prognosis of 13q14 deletion. CONCLUSION: (1) i-FISH followed CD138 cell sorting appears to be a highly sensitive method for detecting 13q14 deletion. (2) 13q14 deletion rate by i-FISH > 25% is an independent unfavorable factor. (3) Bortezomib could reverse the poor prognosis of 13q14 deletion.

[Influence of immunomagnetic sorting on detecting genetic aberration of multiple myeloma cells by interphase fluorescence in situ hybridization].

This study was to aimed investigate the influence of immunomagnetic sorting on detecting the genetic aberrations of multiple myeloma (MM) by interphase fluorescence in situ hybridization (FISH) and to explore the detection method suitable to use in our country. The genetic aberrations of immunomagnetically sorted and unsorted bone marrow cells from the same MM patients were detected by interphase FISH and the detectable rate of genetic aberration was compared. The types of probes included 13 q14 (RB-1) and 14q32 (IGH). The 42 and 22 sorted and unsorted marrow samples from MM patients were detected by using 13q14 probe and 14q32 probes respectively, the results indicated that the 13q14 deletion was found in 9 of 42 (21.4%) unsorted marrow samples and in 25 of 42 (56.8%) CD138(+)-sorted marrow samples. The 13q32 rearrangement was found in 7 of 22 (31.8%) unsorted marrow samples and in 14 of 22(63.6%) CD138(+)-sorted marrow samples. Both of the difference was statistically significant (p = 0.001 and p = 0.035 respectively). Percentages of cytogenetic alterations detected in unsorted bone marrow cells correlated positively with percentage of plasma cells tested by bone marrow smears or flow cytometry. When percentage of plasma cells tested by bone marrow smears exceed 50%, or by flow cytometry exceed 10%, there was no difference between 2 methods. It is concluded that immunomagnetic sorting of CD138(+) cells increases the probability of detection of the 13q14 deletion and 14q32 rearrangement in bone marrow samples. The low detectable rate of genetic aberration in unsorted bone marrow cells is associated to the low percentage of plasma cells in bone marrow samples, higher percentage of plasma cells can partly overcome the shortage of unsorted detection method. When percentage of plasma cells tested by bone marrow smears exceed 50%, or by flow cytometry exceed 10%, there was no difference between 2 methods.

[Cytogenetic and clinical study on 126 cases of B cell non-Hodgkin's lymphoma with bone marrow involvement].

OBJECTIVE: To study the cytogenetic characteristics of B cell non-Hodgkin's lymphoma (B-NHL) with bone marrow involvement, and to explore the clinical significance and prognosis. METHODS: Clinical data of 126 B-NHL patients with bone marrow involvement diagnosed in our hospital were retrospectively analyzed. Chromosome banding analysis was performed after 24 h culture. RESULTS: (1) The B-NHLs included were diffuse large B-cell lymphoma (DLBCL) 38.9% (49 cases), lymphoplasmacytic lymphoma (LPL) 19% (24 cases), mantle cell lymphoma (MCL) 16.7% (21 cases), follicular lymphoma (FL) 9.5% (12 cases), marginal zone lymphoma (MZL) 8.7% (11 cases) and small lymphocytic lymphoma (SLL) 7.1%(9 cases). (2) Chromosome aberrations (CA) were detected in 52 of 126 patients (41.3%) by conventional cytogenetics (CC), including clonal CA 38 cases, and non-clonal CA 14 cases. Ploidy levels in 38 clonal CA cases were pseudodiploid (57.9%), hypodiploid (15.8%) and hyperdiploid (26.3%). The incidence of chromosomal abnormalities among DLBCL, MCL, MZL, LPL, FL and SLL was 73.4%, 38.1%, 36.4%, 8.3%, 8.3% and 11.1%, respectively. (3) Clonal CA, CA more than two kinds, and CA of chromosomes 2, 3, 9, 11, 17, 18 and 20 were associated with shorter overall survival (OS) in DLBCL. More than two kinds of CA and CA of chromosome 3, 13 were associated with shorter OS in MCL. CONCLUSIONS: The incidence of CA was higher in aggressive lymphoma than in indolent lymphoma. Complex CA were quite common, and some specific CA might have prognostic significance.

[Expression of microRNA-223 and its clinical value in B lymphoproliferative disorders].

OBJECTIVE: To detect the expression of microRNA-223 and analyze its clinical value in B lymphoproliferative disorders. METHODS: Peripheral blood samples (n = 78) and bone marrow samples (n = 9) were collected from patients with chronic lymphocytic leukemia (CLL, n = 53), mantle cell lymphoma (MCL, n = 13), splenic marginal zone lymphoma (SMZL, n = 9) and healthy donors (n = 12) at our hospital from 2003 to 2010. Mononuclear cells were isolated and B cells purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and the expression of microRNA-223 measured by TaqMan microRNA quantitative polymerase chain reaction (PCR). The clinical data of these patients were collected and their outcomes analyzed with SPSS 16.0 software. RESULTS: (1) The levels of microRNA-223 in CLL, MCL and SMZL were 4.58 ± 0.62, 4.03 ± 0.54 and 4.63 ± 0.57 respectively. And they were significantly lower than that in normal B cells (5.69 ± 0.60, P < 0.01). The expression of microRNA-223 decreased significantly in MCL versus CLL and SMZL (P < 0.05). There was no statistical difference between CLL and SMZL (P > 0.05). (2) The down-regulation of microRNA-223 was associated with disease aggressiveness in CLL. Patients with unmutated immunoglobulin heavy chain variable region (IgVH) expressed significantly a lower level of microRNA-223 (4.05 ± 0.69 vs 4.67 ± 0.51, P = 0.003). In 13q-negative patients, the expression of microRNA-223 decreased more significantly than that in 13q-positive patients (4.25 ± 0.67 vs 4.76 ± 0.45, P = 0.044). (3) Using receiver operating characteristic (ROC) curve analysis, the microRNA-223 cutoffs were defined according to the IgVH mutational status. The patients were divided into the positive and negative subgroups. The median progression-free survival (PFS) of microRNA-223 positive patient subgroup was 48 months. It was significantly longer than the negative subgroup (P = 0.001). In the microRNA-223 positive subgroup, no patient died at the end of follow-up. CONCLUSIONS: MicroRNA-223 may play an important role in the pathogenesis of B lymphoproliferative disorders. The down-regulation of microRNA-223 is associated with disease aggressiveness and poor prognostic factors in CLL. It may become a new reliable prognostic predictor.

[Overrepresentation of specific gene segments of expressed immunoglobulin heavy chain variable region among unmutated and mutated patients with chronic lymphocytic leukemia].

OBJECTIVE: To investigate the overrepresentation of specific gene segments of immunoglobulin heavy chain variable region (IgVH) among unmutated and mutated chronic lymphocytic leukemia (CLL) patients and its prognostic implication. METHODS: Multiplex PCR was used to identify the expression of IgVH segment and its mutation status in CLL. RESULTS: Analyses were successfully performed in 80 of 85 samples. Marked skewed IgVH families were disclosed. The most commonly used VH was VH3 (40.0%), followed by VH4 (30.0%), VHI (13.8%), VH2 (10.0%) and VH5, VH7 (2.5%). Fifty-six patients (70.0%) had mutated VH, 24 (30.0%) unmutated VH. Nine cases (11.3%) were with 100% germline sequence. Fifteen cases (15/24, 62.5%) in VH4, 29 (29/32, 90.7%) in VH3, and 4 (4/11, 36.3%) in VH1 had mutated VH. The most frequently used IgVH gene was VH4-39 (13.8%), and VH4-34 (8.8%). J4 (36/66, 54.5%) and D3 (25/66, 37.8%) were the most frequently used in J and D genes. The progression-free survival (PFS) was 82 and 17 months (P = 0.000), and the overall survival (OS) was 90 and 41 months (P = 0.009), respectively, for mutated and unmutated cases. Recurrent CDR3 sequences were found in our patients and 2 patients with VH1-69 had CDR3 sequences highly similar to those reported in literature. CONCLUSION: There is difference in IgVH gene segment usage and mutational status in different area CLL patients. Recurrent CDR3 sequences were found in specific IgVH gene segments, which highlights the importance of immunoglobulin mediated stimulation in the development of CLL.

[Clinical and laboratory studies of 11 acute myeloid leukemia patients with t(7;11) (p15;p15) translocation].

OBJECTIVE: To investigate clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with t(7;11)(p15;p15). METHODS: Eleven patients with t(7;11)(p15;p15) were retrospectively reviewed involved in cell morphology, immunophenotype, cytogenetics as well as clinical features and prognosis. RESULTS: Eight patients out of the eleven were female, six patients were AML-M2a, two M4, two M5, and one M6. All the 11 cases expressed CD33, 10 expressed CD117 and CD13, HLA-DR and CD34 was expressed in 7 and 6 patients, respectively. Karyotypes of all the patients were t(7;11) (p115;p15), additional trisomy 8 were found in only one patient. FLT3-ITD was positive in one of nine patients who were analysed for FLT3-ITD and FLT3-TKD. Two patients were alive, and one lost to followed up, while the rest of eight were dead. CONCLUSION: The t(7;11) (p15;p15) abnormalities is one of rare chromosomal translocation in patients with AML. AML patients with t(7;11) (p15;p15) have clinical features of anemia, thrombocytopenia, higher white blood cell, and poor prognosis.

[The expression of microRNA-155 and microRNA-146a and its' clinical value in chronic lymphoproliferative disorders].

OBJECTIVE: To investigate the expression of microRNA-155 and microRNA-146a in the CD19(+) B cells of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and to analyze its clinical significance. METHODS: Peripheral blood (PB) (78 cases) and bone marrow (BM) samples (9 cases) from 53 CLL patients, 13 MCL patients, 19 SMZL patients, and 12 healthy donors were collected. Mononuclear cells were isolated and B cells were purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and microRNAs expression were measured using the TaqMan microRNA quantitative PCR. The results combined with the clinic data of patients were analysed. RESULTS: (1) The expression of microRNA-155 in CLL (4.49 ± 0.83) was significantly higher than in MCL (3.83 ± 0.45) and SMZL (3.80 ± 0.61) (P < 0.05); (2) The level of microRNA-146a in SMZL (3.81 ± 0.59) was significantly higher than in CLL (2.58 ± 0.90) and MCL (2.27 ± 0.88) (P < 0.01); (3) The level of microRNA-155 was significantly higher in IgVH unmutated patients than in mutated patients in CLL (P = 0.012); (4) The microRNAs expression had no statistical difference between two prognostic groups in CLL. CONCLUSION: (1) The expression of microRNA-155 and microRNA-146a is different in malignant lymphoproliferative disorders (LPD); (2) Deregulation of the microRNAs expression might play a critical role in the pathogenesis and prognosis in the LPD.

[Imatinib combined with modified hyper-CVAD/MA followed by allogeneic hematopoietic stem cell transplantation in CR1 as the front-line therapy for adult Ph(+) acute lymphoblastic leukemia].

OBJECTIVE: To explore the efficacy of imatinib (IM)-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-SCT) in first complete remission (CR1) for adult Ph(+) acute lymphoblastic leukemia \[Ph(+)-ALL\]. METHODS: From March 2006 to December 2010, 16 adult Ph(+)-ALL were enrolled in the study. All patients received IM combined with standard VDCP ± L as induction therapy then intensive consolidation with modified Hyper-CVAD/MA regimen plus IM, and followed by allo-SCT in CR1. Some of them received IM maintenance therapy after allo-SCT. With the follow up to March 31, 2011, the clinical parameters. overall survival (OS), disease free survival (DFS), relapse incidence (RI), non-relapse mortality (NRM) and prognostic factors were analyzed. RESULTS: All 16 patients achieved morphological complete remission (CR), and 10 of them achieved molecular CR. After transplantation, all patients obtained successful engraftments. With a median follow-up of 27.1 (7.4 - 65.8) months, 14 patients were alive, 2 died from NRM, and 2 relapsed. The estimated OS and DFS at 3 year were (85.9 ± 9.3)% and (83.9 ± 10.5)%, and cumulative RI and NRM at 3 year were (16.1 ± 10.5)% and (14.1 ± 9.3)%, respectively. None prognostic factor was found on analysis. CONCLUSION: IM combined with intensive chemotherapy significantly increased the CR rate and improved the quality of CR, which prepared the feasibility of allo-SCT in CR1. IM therapy pre- and post-allo-SCT would be a promising strategy for adult Ph(+)-ALL to decrease relapse and facilitates favorable OS and DFS.

[Expression of stereotyped B-cell receptor and its clinical value in chronic lymphocytic leukemia].

OBJECTIVE: To investigate the expression pattern of stereotyped B-cell receptor (BCR) and its prognostic significance in Chinese chronic lymphocytic leukemia (CLL) patients and evaluate the relationship to other prognostic markers. METHODS: Multiplex polymerase chain reaction (PCR) was used to identify the immunoglobulin variable heavy-chain (IGHV) segment and its mutation status in 116 CLL patients from April 1992 to April 2010. For CDR3-driven clustering, all in-frame IGHV-D-J rearrangements were aligned by the multiple sequence alignment software ClustalW2. RESULTS: There were 102 of 116 samples from newly diagnosed CLL were successfully analyzed. IGHV CDR3 genes were identified in 73/102 cases. Fourteen patients (19.2%) carried stereotyped BCR. A high percentage of carried stereotyped BCR was observed in IGHV non-mutated group versus mutated group (40.9% vs 11.8%, P = 0.005). Patients with stereotyped BCR had a higher frequency of deletion (17q) (33.3% vs 10.7%, P = 0.045). The median progression-free survival (PFS) in patients with stereotyped BCR was much shorter than other patients (39 vs 84 months, P = 0.002). CONCLUSION: The patients with stereotyped BCR have a poor prognosis. It highlights the importance of immunoglobulin mediated stimulation in the development of CLL.

Comparison among immunologically different subtypes of 595 untreated multiple myeloma patients in northern China.

BACKGROUND: Generally, characteristics of heterogeneous multiple myeloma (MM) have been described as a whole. Actually, isolated immunologic subtypes of MM may be associated with prognostic significance. PATIENTS AND METHODS: The aim of this retrospective single-center study was to determine the characteristics of immunologically different subtypes among 595 evaluable cases with previously untreated MM in northern China. RESULTS: The major distribution of MM subtypes were immunoglobulin (Ig)G, 47.9%; IgA, 23.3%; and light-chain, 21.0%. Nonsecretory, IgD, and biclonal subtypes were rarely seen, comprising only 7.7%. The male-to-female ratio was 1:7, and the median age was 59 years. In the IgG subtype, more patients presented with elevated M protein, fulfilling the major diagnostic criteria determined by Durie, and infection occurred more frequently; however, the prognosis was favorable. In the IgA subtype, in which survival was significantly poorer, the extent of anemia was more severe, and nonhyperdiploid abnormality may be its adverse indicator. In the light-chain subtype, the mean level of serum IL-6 was the highest, and more patients presented with advanced renal dysfunction, bone destruction, and thrombocytopenia. However, more light-chain patients were staged at International Staging System I, partially resulting in the favorable median survival of 51 months (almost equivalent to 50 months with the IgG subtype). Another rare subtype with unfavorable outcome was IgD myeloma, in which the median age was 50 years, and the serum calcium level was significantly decreased. Intriguingly, we also noted that more patients presented hypocalcemia than hypercalcemia (37.7% vs. 15.7%) in the current series. Multivariate analysis revealed that independent adverse indicators included age > 50 years, Durie-Salmon stage III, and increased values of C-reactive protein and beta2-microglobulin. CONCLUSION: The median duration of survival in MM reached 36.0 months. Distinctions among immunologically different subtypes can predict prognostic significance, namely, favorable in IgG and light-chain subtypes but significantly poorer in IgA and IgD subtypes.

[The significance of hematopoietic cell genetic instability in aplastic anemia.].

OBJECTIVE: To evaluate bone marrow hematopoietic cells genetic instability (BMHCGI) in patients with aplastic anemia (AA) and to explore its influence on immunosupressive therapy for AA and significance on late clonal hematologic disorders. METHODS: Genetic instability of bone marrow mononuclear cells (BMMNC) was measured by Comet assay. The relationship between bone marrow failure parameters and genetic instability results was evaluated. The reciprocity of genetic instability and treatment responses to immunosuppressive therapy (IST) was investigated. RESULTS: Comet assay parameters \[tail moment (TM), olive TM (OTM), comet %\] of AA patients were significantly higher than that of control group (P < 0.05). There was no statistic correlation of comet parameters of severe AA (SAA) BM hematopoietic cells with age, gender and peripheral blood cell count (P > 0.05). For the treatment response rate at six months after IST there was no statistical difference between comet cells of < 21.64% and of >/= 21.64%, and so did between OTM < 1.58 and >/= 1.58 in SAA patients. IST had no effect on SAA BMHCGI, whereas, the Comet%, TM and OTM in SAA PR patients and Comet% in CR patients were significantly decreased than those before treatment. Comet parameters of two SAA patients were significantly increased before the development of clonal cytogenetic abnormalities. CONCLUSIONS: Increased BMHCGI may be one of the elements in the pathogenetic mechanisms in AA. The genetic instability is irrelevant to the SAA patients overall response rate of IST at six months, but IST can alleviate the genetic instabilities in responded SAA patients.

Clinical Features of Bone Complications and Prognostic Value of Bone Lesions Detected by X-ray Skeletal Survey in Previously Untreated Patients with Multiple Myeloma.

Multiple myeloma is usually associated with the presence of lytic bone lesions. We reviewed the clinical and laboratory features of patients with newly diagnosed myeloma bone disease and evaluated the prognostic significance of different X-ray image patterns in symptomatic MM patients. We retrospectively reviewed 260 patients with newly diagnosed MM. X-ray image patterns of patients were correlated with hematologic parameters, therapeutic reaction and patient survival. Patients with the X-ray imaging pattern of grade 2-4 had significantly higher marrow plasma cells levels, marrow CD138(+) D38(+) cell percentage, ECOG performance score, and serum IL-6 level than grade 0-1. Univariate analysis demonstrated that skeletal lytic changes associated with rapid progression. There is a high incidence of myeloma bone disease (MBD) in patients of MM in China. Patients of extensive bone lesions have more severe alterations in hematologic parameters than do those without bone lesions and severe bone lesions is an important adverse prognostic factor associated with a short TTP.