Study of iron overload assessment by T2* magnetic resonance imaging in patients with myelodysplastic syndromes / 中华血液学杂志

Objectives@#To analyze the cardiac T2* value, liver iron concentration (LIC) , and related laboratory parameters in myelodysplastic syndrome (MDS) with iron overload and evaluate the changes of organ functions after iron chelation therapy. To explore the value of magnetic resonance imaging (MRI) T2* in making early diagnosis and assessing organs iron overload.@*Methods@#Retrospective investigation was used to observe the cardiac T2* value, LIC, iron metabolism parameters and related laboratory parameters of 85 MDS patients from Nov 2014 to Jan 2018. Among them, 7 MDS patients with Low/Int-1 have received iron chelation therapy for 6 months during two MRI examinations. The above parameters were collected before and after iron chelation therapy for comparison.@*Results@#Correlations were found between heart T2* value and age (rs=-0.290, P=0.007) and left ventricular ejection fraction (LVEF) (rs=0.265, P=0.009) . There was a significant negative correlation between heart T2* value and blood transfusion units (rs=-0.701, P<0.001) . There was a significant positive correlation between LIC and serum ferritin (SF) (rs=0.577, P<0.001) . There was also a correlation between LIC and ALT (rs=0.268, P=0.014) and blood transfusion units (rs=0.244, P=0.034) . There was no correlation between heart T2* and pro-BNP, SF (all P>0.05) , and no correlation between LIC and age (P>0.05) . The increase of heart T2* between the normal and abnormal groups was statistically significant (P=0.005) , but the iron overload ratio of the heart T2*<20 ms was not significant between the two groups. There was statistical significance in the proportion of severe liver iron overload (LIC>15 mg/g DW) (P=0.045) . After iron chelation therapy, the values of SF, transferrin saturation, ALT, AST, pro-BNP and LIC of 7 patients were decreased compared with values before iron chelation therapy, and the peripheral blood cell level was increased. However, the changes of LVEF and T2* values after iron chelation were not obvious.@*Conclusion@#MRI T2* may be a predictor of iron overload in patients with MDS in early stage, and may be more valuable compare with LVEF, SF and other laboratory indicators. The safety and repeatability of MRI cardiac T2* examination are recognized, and it can be used as an ideal detection for patients with iron overload.

Predict response to decitabine in patients with myelodysplastic syndrome and related neoplasms / 中华血液学杂志

Objective@#To identify clinical and molecular signatures for predicting response to decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and related neoplasms.@*Methods@#The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment.@*Results@#Of 109 MDS and related neoplasms patients, there were 70 males and 39 females, the median age was 61 years old (ranges: 17-85 years old) . According to the international prognostic scoring system (IPSS) , 46 cases were included in the relatively low risk group (low risk and intermediate-1 risk) , 63 in the relative high risk group (intermediate-2 and high risk) . There were 21 cases with complex karyotype, 17 chromosome 7 abnormality and 17 monosomal karyotype. The median courses of DAC treatment was 4 (2-11) . A total of 74 patients achieved response (67.9%) and 30 (27.5%) achieved complete response (CR) . Univariate analysis found that CR was higher in patients with high risk of IPSS, complex karyotypes, monosomal karyotypes, chromosome 7 abnormality, and platelet doubling after one cycle of DAC treatment. Patients with TP53 gene mutation were more likely to receive CR, 10 of 15 patients with TP53 mutations achieved CR. (66.7%) , which was significantly higher than that of the patients without TP53 gene mutation (21.3%) (P=0.001) . Multivariate analysis showed that TP53 gene mutation, platelet doubling after one cycle of DAC treatment and the complex karyotype were independent prognostic factors for CR. Of them, TP53 gene mutation is the strongest predictor (OR=4.39, 95%CI, 1.20-16.06, P=0.026) .@*Conclusion@#TP53 mutation, platelet doubling after one cycle of DAC treatment and complex karyotypes could predict CR to DAC.

MRI for assessment of iron overload in patients with hematologic disease / 中华血液学杂志

<p><b>OBJECTIVE</b>Compare the characteristics of magnetic resonance imaging（MRI）liver T2*, cardiac T2* and serum ferritin on the assessment of iron overload.</p><p><b>METHODS</b>A total of sixty-nine patients from November 2011 to June 2014 were enrolled in this study. Their cardiac and liver iron concentration levels were measured through MRI examination, with other clinical data were collected to perform statistical analysis.</p><p><b>RESULTS</b>The correlation between liver T2* and adjusted serum ferritin（ASF） was statistically significant（P=0.003）. However, no significant correlation was found between cardiac T2* and liver T2*, ASF, respectively. According to the statistical analysis of the 69 cases, it is found that the number of iron overload cases diagnosed by liver T2* was 62 and 20 cases were severe iron overload （32.26%）; the number of iron overload cases diagnosed by ASF was 47 and 14 cases were severe iron overload（29.79%）, while the number of iron overload cases diagnosed by cardiac T2* was only 25 and no severe iron overload cases.</p><p><b>CONCLUSION</b>Since SF was affected by other factors, it cannot reflect the level of iron overload in human body objectively. Now, liver T2* has become the gold standard for assessment of iron overload because of its good reliability and repeatability. However, cardiac T2* cannot correctly be used as assessment for iron overload, and it is only a method of evaluating the level of cardiac iron deposition.</p>

Multisystem Langerhans cell histiocytosis with diabetes insipidus as the first symptom: a case report and literature review / 白血病·淋巴瘤

Objective To study the clinical features and differential diagnosis of Langerhans cell histiocytosis (LCH).Methods A case of LCH was reported and the literatures were reviewed.Results The of multisystem LCH patient,presented with a diabetes insipidus (DI) and panhypopituitarism,was 44 years old,and developed costal,tibial and femoral multiple lesions.The final diagnosis as LCH was made based on biopsy of tibia and lymph nodes.The biopsy specimen showed that the cells were infiltrated exhibiting the characteristic morphologic features of Langerhans cell (LC) with a convoluted shape,elongated nuclei exhibiting longitudinal grooves,and immunohistochemistry results revealed positive LC for the S-100,CD1a and Langerin immunostaining.Conclusions LCH may range from a solitary lytic bone lesion (for example eosinophilic granuloma) with a favorable course to a fatal disseminated leukaemia-like form.LCH typically involves the bone,lesions almost can be found in all organs.DI and CNS involvement often present as a puzzling syndrome,which renders the diagnosis problematicly,and often delays the diagnosis of LCH.The damage to the pituitary/hypothalamus axis results in life-long hormonal replacement therapy.

The use of selective immunosuppressive therapy on myelodysplastic syndromes in targeted populations results in good response rates and avoids treatment-related disease progression.

To determine the treatment response and disease progression in strictly selected patients with myelodysplastic syndrome undergoing immunosuppressive therapy (IST), patients were required to have an international prognostic scoring system [corrected] (IPSS) score ≤ 1.0 and at least one of the following conditions: (1) expression of the HLA-DR15 allele, (2) bone marrow (BM) cellularity of less than 30%, and (3) abnormal immune index of BM T-lymphocytes.The exclusion criteria were as follows: (1) ≥ 5% marrow myeloblasts, (2) poor karyotype, and (3) diagnosis of concurrent nonhematological malignancy. Patients received antithymocyte globulin followed by cyclosporine A (CsA) or CsA alone for at least 3 months. Seventy-one cases were analyzed. The total response rate was 77.5% (55/71 cases) with 11 complete responses. The response rate was positively correlated with the number of recruitment criteria met. Patients with an abnormal CD8, an abnormal CD4, or both had similar response rates. Patients who responded to treatment had significantly lower Th1 and Tc1 levels after treatment (P < 0.01 and P < 0.001, respectively), and six of eight patients with abnormal chromosomes did not show obviously abnormal clonal expansion when reassessed after IST. During the median observation period of 24 months, only two cases exhibited disease progression. At the median observation of 24 months, 35 of 55 responders (63.6%) maintained a hematological response, and 60 of 71 patients (84.5%) were still alive. The strictly selective use of IST may yield high response rates and can avoid treatment-related acute myeloid leukemia transformation. IST significantly reduces Th1 and Tc1 levels without causing malignant clonal expansion.

Experimental and clinical characteristics in myelodysplastic syndrome patients with or without HLA-DR15 allele.

We studied the effects of the presence of the HLA-DR15 allele on the experimental and clinical features of myelodysplastic syndrome (MDS) by assessing the clinical data of 136 patients with MDS. We observed that the frequency of HLA-DR15 expression in MDS patients (38.7%) was significantly higher than that in the healthy controls (p < 0.01). We noted the following observations with regard to disease progression: None of the 46 HLA-DR15 positive patients with international prognostic scoring system (IPSS) scores or=1.5 and the presence of >or=5% blasts in the bone marrow in the DR15-positive patients were lower than the corresponding findings in the DR15-negative patients. In addition, we also recorded the following observations with regard to bone marrow (BM) failure: The bicytopenia/pancytopenia ratio in the DR15-positive patients was higher than that in the DR15-negative patients (92.4 vs. 78.3%; p = 0.029). The peripheral-neutrophil count and the platelet count in the DR15-positive patients were lower than those in the DR15-negative patients (p = 0.028 and p = 0.011, respectively). Moreover, hypocellularity was more easily detectable in the DR15-positive patients (26.4 vs. 16.9%). In addition, the BM CD4+ lymphocyte count and the CD4/CD8 ratio in the DR15-positive patients were higher than the corresponding values in the DR15-negative patients (p < 0.05 for both). However, there were no significant differences between the polarization of T-helper (T(h)) and T-cytotoxic (T(c)) cells and the cytokine levels in these two patient groups. We concluded that the presence of the HLA-DR15 allele is indicative of a genetic susceptibility to MDS and, the presence of the HLA-DR15 allele showed less association with disease progression and greater association with BM failure.

The role of mesenchymal stem cells in supporting haemopoiesis and differentiation / 白血病·淋巴瘤

Mesenchymal stem cells(MSC) have the ability to self-renew and differentiate into tissues of mesodermal origin (osteocytes, adipocytes, chondrocytes), and the cellular constituents of the microenvironment, largely derive from a common progenitor of mesenchymal origin. MSC themselves and their large numbers of progeny form three kinds of niches(osteoblastic niche, stromal niche and adipocyte niche)which have a fully competent microenvironment to provide appropriate signals via production of soluble factors and cell contact interactions of adhesion molecules, by which they play the role in supporting haemopoiesis and differentiation. Many of the discoveries described herein may contribute to future clinical treatments for hematopoietic, including cancer.

Diagnosis of unknown nonhematological tumors by bone marrow biopsy: a retrospective analysis of 10,112 samples.

PURPOSE: To investigate how unselected bone marrow (BM) biopsy examinations could help in the diagnosis of clinically unknown nonhematological tumors. METHODS: 10,112 plastic-embedded BM biopsy sections were retrospectively analyzed. In the analysis we focused on the following aspects: (1) the frequency of BM involvement arising from clinically unknown nonhematological malignancies, (2) the clinical indication for BM biopsy examination in cases with tumor BM metastasis, (3) the primary sites of the metastatic tumors, and (4) the advantage of plastic-embedded biopsy sections over paraffin-embedded samples and the complementarity of biopsy with aspiration smears. RESULTS: Of the 10,112 BM samples analyzed, 101 (1.0%) were interpreted as being nonhematological tumor metastases. In cases with metastatic tumors, the nonhemocyte-related changes, such as skeletal pain (25%) and bone destruction (5%), were considerably higher than in those without metastasis (3.7 and 0.32%, respectively; P < 0.001). Primary lesions were documented antemortem in 50 of the 101 biopsy-positive cases (49.5%); the most frequent being in the lung, gastric tract, and breast. Using this assay, a higher incidence of metastatic tumors was detected when compared with previously reported paraffin-embedded samples. The frequency of metastatic tumors based on aspiration smears when the positive results for biopsy sections were used as a reference was 74.3%. All the 101 sections with metastatic tumors showed various degrees of myelofibrosis. CONCLUSIONS: We concluded that the routine BM biopsy examination is helpful in detecting insidious metastatic nonhematological malignancies. Skeletal pain and bone destruction are critical indications for susceptible patients to undergo BM examination. Plastic embedding of biopsy sections appears to be more sensitive than the paraffin embedding of samples and is an excellent complementation to isolated aspiration smears.

Induction chemotherapy with low-dose homoharringtonine, cytarabine, and granulocyte colony-stimulating factor priming in patients with advanced myelodysplastic syndrome or post-myelody splastic syndrome acute myeloid leukemia / 中国医师进修杂志

20?10~9/L. This regimen was given for one course for induction, and was followed by conventional chemotherapy as maintenance or consolidation when complete remission(CR) achieved, or succeeding with other treatment when no response could be observed. Results Six patients achieved CR (54.5%) and one achieved partial remission (PR)(9.1%) with one course of treatment. Among 6 of 11 patients with CR, 5 relapsed at 2,3,6,8 and 16 months respectively. Three relapsed patients were retreated with the same protocol but achieved only one partial responses. Nine of the 11 patients had been died and their mean survival (since induction chemotherapy) was 9.2 months. Infectious complications during cytopenia were less serious than conventional chemotherapy withno treatment-related.Conclusion This moderate intensity protocol with G-CSF priming is effective and safe but remissions are of short duration.