Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia / 中华儿科杂志

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Effect of human umbilical cord mesenchymal stem cells on the CD34+ cells transplantation in NOD/SCID mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of human umbilical blood (UB) mesenchymal stem cells (MSC) on the CD34(+) cells transplantation in NOD/SCID Mice.</p><p><b>METHODS</b>Umbilical blood CD34(+) cells (3.5 x 10(5) cells) alone or combined with umbilical cord MSC cells were transplanted into NOD/SCID mice that had been irradiated with (137)Cs (3.0 Gy) before transplantation. Changes in peripheral blood cells within 6 post-transplantation weeks were detected. The mice were sacrificed 6 weeks after transplantation. The human hematopoietic cells (hCD45(+)) and multi-lineage engraftment cells (CD3/CD19, CD33, CD14, CD61, and CD235a) in NOD/SCID recipients bone marrow, spleen, and peripheral blood were analyzed by flow cytometry.</p><p><b>RESULTS</b>In the 3rd post-transplantation week, white blood cells (WBC), platelets (PLT), and red blood cells (RBC) began to increase in both two groups. In the 6th post-transplantation week, WBC and PLT counts in CD34(+) + MSC group reached peak levels and were significantly higher than CD34(+) alone group (P < 0.05), while RBC level was not significantly different between these two groups P > 0.05). hCD45(+) cell levels in bone marrow and peripheral blood were (42.66 +/- 2.57) % and (4.74 +/- 1.02) % in CD34(+) + MSC group, which were significantly higher than those in CD34(+) alone group [(25.27 +/- 1.67) % and (1.19 +/- 0.54) %, respectively, P = 0.006]. Also in the 6th post-transplantation week, the proportions of CD19(+), CD33(+), CD14(+), CD61(+), and CD235a(+) in CD34(+) + MSC group were significantly higher than those in CD34(+) alone group (P < 0.05), while the proportion of CD3(+) T lymphocyte in CD34(+) + MSC group was significantly lower than that in CD34(+) alone group (P = 0.003). The amplification of CD19(+) B lymphocyte was significantly higher than other blood cell lineages (P < 0.05).</p><p><b>CONCLUSION</b>The co-transplantation of MSC cells and CD34(+) cells can promote hematopoietic stem cell transplantation and hematopoietic recovery in vivo.</p>

Study of influence of umbilical cord mesenchymal stem cells on CD34+ cells in vivo homing in NOD/SCID / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect and the potential mechanism of umbilical cord (UC) derived mesenchymal stem cells (MSCs) on umbilical cord blood (UCB) derived CD34+ cells in vivo homing in xenotransplanted NOD/SCID mice model.</p><p><b>METHODS</b>CD34+ cells and MSCs were derived from fresh UCB and UC, respectively. CD34+ cells (5 x 10(5) per mice) and MSC cells (5 x 10(6) per mice) were co-transplanted into irradiated NOD/SCID mice intravenously. CD34+ cells (5 x 10(5) per mice) alone were transplanted into the mice as control group. CD34+ cells home in bone marrow and spleen of recipient mice were detected 20 hours after transplant by FACS and RT-PCR, and the homing efficiencies were calculated. The effect of MSCs on CD34+ cells chemotactic function was investigated after co-cultured UCB CD34+ cells with UC MSCs in vitro. After 4 and 7 days coculture, the homing related adhesion molecules (the CD49e, CD31, CD62L, CD11a) expressed on CD34+ cells were detected by FACS.</p><p><b>RESULTS</b>1) The homing efficiencies in bone marrow in experimental and control group were (7.2 +/- 1.1)% and (5.4 +/- 0.9)%, respectively (P < 0.05). 2) Human GAPDH gene was detected in bone marrow in experimental group and in spleen in both groups. 3) The migration efficiency of CD34+ cells was significantly higher in experimental group (35.7 +/- 5.8)% than in control group (3.5 +/- 0.6)% (P < 0.05). 4) The expression of CD49e, CD31, CD62L on CD34+ cells kept higher level in MSCs cocultured group than in CD34+ cells alone group.</p><p><b>CONCLUSIONS</b>MSCs can efficiently increase homing of CD34+ cells to bone marrow and spleen in vivo by keeping a high level of homing adhesion molecules expression and improving migration efficiency of UCB CD34+ cells.</p>

The efficacy of thalidomide for multiple myeloma: a clinical analysis of 102 Chinese patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the efficacy and safety of thalidomide (Thal) for patients with multiple myeloma (MM).</p><p><b>METHODS</b>Effectiveness and adverse events of 102 MM patients treated with thalidomide at a median dosage of 200 mg/d. Thirteen cases were treated with Thal alone (group A), and 105 case with Thal in combination with other therapeutic agents (group B) were retrospectively analyzed.</p><p><b>RESULT</b>1) The response rate (RR) (CR + PR) was 65.4% for induction therapy in 52 cases and 45.5% for salvage therapy in 66 cases. RR in group B was higher than that in group A (58.1% versus 23.1/%, P= 0.017), and the non-response/progress (NR) rate was lower (15.2% versus 46.2%, P= 0.015). In group B, the NR rate was lower in 50 cases of newly diagnosed MM than in 55 cases of refractory or relapsed MM (6.0% versus 23.6%, P=0.012). In group B, RR between Thal+VAD or M, regimen (72 cases) and Thal + MP regimen (33 cases) was not statistically significant (62.5% versus 48.5%, P >0.05). 2) The median duration of response maintenance was 15.5 (1.0-58.0) months in 21 cases. 3) Among 97 patients with follow-up data, the estimated median duration of OS was 44 months in a median follow-up duration of 20 months and the accumulative time for use of Thal was 8 months. In univariate analysis,the accumulative duration for use of Thal 6 months, hemoglobin > or = 100 g/L and bone marrow megakaryocytes > 20 per smear were associated with longer OS (P = 0.0014, 0.0101, 0.019, respectively). 4) Multivariate analysis suggested that the accumulative time for use of Thal and bone marrow megakaryocytes > 20 were independent good prognostic factors for OS (P = 0.006, 0.036, respectively). 5) The adverse events of Thal were mostly endurable, the rate of thrombus events was lower than that reported in literature.</p><p><b>CONCLUSION</b>Thalidomide alone or combined with chemotherapy is an useful therapy for MM. The accumulative time for use longer than 6 months may improve survival.</p>

The analysis of prognostic variables in 123 patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the prognostic value of biological features and therapy-related factors in multiple myeloma (MM).</p><p><b>METHODS</b>123 patients with newly diagnosed MM between January 1998 and May 2005 were enrolled in this retrospective study. Biological features at presentation and therapy-related factors were analysed. The overall survival (OS) and time to progression (TTP) were estimated by Kaplan-Meier analysis and the distribution of OS and TTP were compared using log-rank test. Cox regression was used to identify the independent prognostic factors.</p><p><b>RESULTS</b>(1) The univariate analysis indicated that more immature plasma cells in bone marrow biopsy, C-reactive protein >8. Omg/L, CD117 expression, serum beta2-microglobulin (beta2-MG) (3.5 approximately 5.5 mg/L), abnormal cytogenetics aberration of chromosome 13 (Delta13), hypodiploid, poor response to chemotherapy, interferon(IFN) therapy less than 6 months were associated with shorter OS(P <0.05). Lytic bone lesions at presentation, more immature plasma cells in bone marrow biopsy, serum beta2-MG (3.5 approximately 5.5 mg/L), poor response to chemotherapy, and IFN therapy less than 6 months as well as abnormal cytogenetics, hypodiploid and Delta13 were associated with shorter TTP (P <0.05). (2) Multivariable COX analysis indicated IFN therapy more than 6 months was a protective factor for OS and TTP, and more immature plasma cells in bone marrow biopsy was an independent poor prognostic factor for TTP.</p><p><b>CONCLUSION</b>The morphology of myeloma cells is useful for assessing the prognosis. And IFN therapy more than 6 months could lengthen OS and TTP.</p>