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.

Recent advances on the prognostic value of immunophenotyping in multiple myeloma by flow cytometry / 中国实验血液学杂志

Clinical application of flow cytometry in multiple myeloma (MM) can be found in various dimensions, such as in differential diagnosis of malignant plasma cell disorder from reactive plasmacytosis, identification of the progression risk in MM, and in the detection of minimal residual disease. Flow cytometry-based clonality assessment with immuno-phenotyping encourages and enables the most stringent method of diagnosis and follow-up. The objective of this review is to summarize the recent information of the malignant plasma cell phenotypic profile of MM. The most comprehensive antigens, such as CD19, CD27, CD28, CD45, CD56 and CD117, play a significant role in the characterization of normal and malignant plasma cells. This review also focuses on the association of malignant phenotypic markers with chromosomal aberrations that identify the specific prognostic factors in MM.

Current understanding of iron overload hazard in patients with myelodysplastic syndrome / 中国实验血液学杂志

Patients with myelodysplastic syndromes (MDS) become dependent on blood transfusions and develop into transfusional iron overload, which is exacerbated by increased absorption of dietary iron in response to ineffective erythropoiesis. However, it is uncertain whether there is an association among iron accumulation, clinical complications, and decreased likelihood of survival in MDS patients. Thereby our current understanding of the effects of transfusion dependency and iron overload in MDS are discussed. Particular emphasis should be placed on further characterizing the role of redox-active forms of labile iron and oxidative stress in iron overload, decreased life expectancy and increased risk of leukemic transformation in MDS patients with iron overload.

Clinical therapeutic efficacy of rituximab for relapsed and refractory idiopathic thrombocytopenic purpura / 中国实验血液学杂志

The aim of this study was to evaluate the effect of rituximab treatments for refractory and relapsed idiopathic thrombocytopenic purpura (ITP). 18 patients with refractory and relapsed ITP who received 22 courses of rituximab treatments from January 2007 to December 2010 were analyzed retrospectively. Rituximab was given at a dose of 375 mg/m(2) intravenously weekly for a continuous 4 weeks. The results indicated that responses were achieved in 15 of 22 (68%) courses, out of which complete responses were achieved in 10 of 22 (45%) courses, partial and minimal responses were achieved in 5 of 22 (23%) courses, and no responses were achieved in 7 of 22 (32%) courses. The median time of response was 3 weeks (1 - 17 weeks) from the start of treatment and median duration of response was 13 weeks (1 week - 42 months). The responses were mostly short-sustained and follow-up median time was 20 months (1 - 52 months). The responses of 8 patients (36%) sustained for over 6 months, 6 patients (27%) sustained for over 1 year, and 4 patients also showed sustained response at last visit of follow-up. Previous splenectomy resulted in a poor response (P = 0.037). Patients who failed in rituximab treatment and prior received multiple treatments including splenectomy, had a poor response to further therapies. It is concluded that rituximab is well tolerated by patients and is useful in some patients with relapsed and refractory ITP, however, only about 20% patients can achieve sustained remissions. The patients who failed in rituximab treatment has a poor response to further treatment.

Comparison of bone marrow biopsy and smear efficacy in patients with multiple myeloma / 中国实验血液学杂志

This study was aimed to explore the significance of the bone marrow biopsy for the diagnosis of multiple myeloma. Bone marrow smears and bone marrow biopsy originated from 279 cases of multiple myeloma were detected and compared in term of bone marrow hyperplasia, bone marrow plasma cell infiltration, proliferation mode, pathological changes in the bone marrow stroma and myelofibrosis. The results indicated that the levels of proliferation in bone marrow biopsy was significantly higher than that in bone marrow smears. Plasma cell proliferation mode in bone marrow biopsy was not completely consistent with the proportion of plasma cells in bone marrow smears. The myelofibrosis level displayed influence on the consistency of the proliferation between bone marrow smears and biopsies. It is concluded that as compared with bone marrow smears the bone marrow biopsy can more accurately reflect the levels of bone marrow hyperplasia and bone marrow plasma cell infiltration, proliferation mode and so on. Bone marrow biopsy is valuable for multiple myeloma diagnosis.

Yield of CD34(+) cells in graft can be increased significantly by G-CSF used at appropriate time after chemotherapy for AutoPBSCT / 中国实验血液学杂志

This study was aimed to investigate the influence of timing using G-CSF after chemotherapy on graft yield of mobilized peripheral blood stem cells for autoPBSCT. 39 patients with lymphoma or multiple myeloma (MM) received the same chemotherapy mobilization regimen, including CTX 400 mg/m² d1; VLB 2 mg/m(2) d1; Ara-C 60 mg/m ²× d1-5; VP-16 60 mg/m² × d1-5; and prednisone 40 mg/m² × d1-5. The historical control group (12 cases) received G-CSF subcutaneously (filgrastim) at the first restoration after the initial nadir of the peripheral WBC count. The experimental group (27 cases) received G-CSF during the steady rise of the WBC count (end of fluctuating after initial nadir). G-CSF was given in a single daily subcutaneous dose of 5 µg/kg until the final PBSC apheresis. When the peripheral WBC and mononuclear cell (MNC) counts reached 10 × 10⁹/L and 1.0 × 10⁹/L respectively, leukapheresis was carried out using the COBE Spectra blood cell separator. The results indicated that despite there was comparable treatment with alkylating agents between 2 groups, a significantly increased yield of CD34 positive cells was observed in the experimental group (26.4 × 10⁶/kg), as compared to the historical control group (3.1 × 10⁶/kg) (p = 0.0031). It is concluded that the appropriate timing for the use G-CSF mobilization after chemotherapy is important to increase the CD34(+) cell yield in auto-graft.

Maintenance treatment of multiple myeloma-review / 中国实验血液学杂志

Chemotherapy with traditional standard dose or autologous stem cell transplantation (ASCT) after chemotherapy with high dose have some remission effect for multiple myeloma, but relapse still exists. The maintenance treatment would prolonged the remission stage. These treatments included the use of alkylating agent, interferon, corticosteroids, thalidomide and so on. Every maintenance treatment has some advantages and some side effects. The truly effective maintenance treatment would not only minimize the harm of the disease, but also would prolong the overall survival, progression-free survival and the event-free survival. This article summarizes the current progress in the maintenance treatments for multiple myeloma.

Efficacy of induction chemotherapy for patients with high-risk myelodysplastic syndrome (MDS) or MDS-transformed acute myeloid leukemia with CHG regimen and its comparison with regimen GAG and HA / 中国实验血液学杂志

This study was aimed to investigate the efficacy of moderate intensity regimen, CHG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor (G-CSF)) on the patients with high-risk MDS or MDS-transformed acute myeloid leukemia. 30 newly diagnosed adult patients with high-risk MDS or MDS-transformed AML were enrolled in this clinical trial to evaluate the efficacy of sequential low-dose homoharringtonine/cytarabine chemotherapy combined with G-CSF priming. Homoharringtonine and Ara-C were injected intravenously at doses of 1 mg and 25 mg daily for 14 consecutive days respectively, G-CSF was injected subcutaneously once daily at a dose of 300 microg on 12 hours prior to chemotherapy and continued given until the end of chemotherapy or when the peripheral WBC count reached > 20 x 10(9)/L. This regimen was given only for one course, and followed by conventional chemotherapy as maintenance or consolidation therapy when CR achieved. 33 patients with high- risk MDS and MDS-transformed AML were injected aclarubicin/Ara-C intravenously at doses of 10 mg and 25 mg for 8 and 14 consecutive days respectively, G-CSF was used at the same dose and the same way as the CHG regimen. 33 patients with high-risk MDS and MDS-transformed AML were treated with HHT/Ara-C intravenously at doses of 2 - 3 mg and 100 - 150 mg daily for 7 consecutive days respectively, G-CSF was injected when WBC count was below 4 x 10(9)/L, and it was stopped to be used when WBC count was > 4 x 10(9)/L. The results showed that (1) 14 patients achieved complete remission (CR) (46.67 %) and 7 patients achieved partial remission (PR) (23.33 %) with one course of CHG regimen, total effective rate was 70%; 14 patient achieved CR (42.4%) and 9 patients achieved PR (27.3%) with one course of CAG regimen, total effective rate was 69.7%; 7 patient achieved CR (33.3%) and 3 patients achieved PR (9.1%) with one course of HA regimen, total effective rate was 42.4%. There was no statistical difference between the effective rate of CHG and CAG, but difference was significant between CHG and HA. (2) Agranulocytosis (neutrophil < 0.5 x 10(9)/L) occurred in 12 cases (40%) of CHG-treated patients with a mean 8 days of agranulocytic period, so the infectious complications were less serious and tolerable without treatment-related death. (3) Among 14 out of 30 patients with CR, 9 relapsed, the mean duration from CR to replace was 8.2 months. All relapsed patients reusing CHG regimen did not achieved CR again. (4) Among 13 cases with CR, 6 patients just received HA or DA regimens as consolidatory and intensive chemotherapy after CR have relapsed, the mean CR time was only 6.1 months. Otherwise, the mean CR time of 7 CR patients received alternative succeeded chemotherapy containing mitoxantrone/idarubicin/THP/homoharringtonine/daunorubicin/aclarubicin after CR was 10.6 months; and among them 4 are still in continuous CR. It is concluded that the CHG chemotherapy regimen has a similar effect with CAG but better than HA, and in a saft chemotherapy regimen with slight myelosuppression in clinical application, strong and alternative succeeded chemotherapy is necessary for CR patients to keep longer CR and survival.

Cytotoxicity of IFN-gamma-activated dendritic cells to freshly isolated acute myeloid leukemia cells / 中国实验血液学杂志

To investigate the tumoricidal activity of dendritic cell (DC) stimulated by interferon-gamma (IFN-gamma) against freshly isolated myeloid leukemia cells and its mechanism, the peripheral blood monocytes collected from healthy donors were cocultured with interleukin-4 and granulocyte-macrophage colony-stimulating factor in medium to induce DC for 7 days. After 12 hour culture in the absence or presence of IFN-gamma, the changes of costimulatory molecules were analyzed with flow cytometry. To assay the cytotoxicity of DC against freshly isolated acute myeloid cells, they were cocultured at various effector-to-target ratio for 18 hours, then the percentage of tumoricidal activity was measured with (51)Cr release assay. To explore the mechanism of DC-mediated cytotoxicity, the change of DC surface or intracellular protein expression of Fas ligand (Fas L), TNF-alpha and TNF related apoptosis-inducing ligand (TRAIL) were analyzed with flow cytometry. The results showed that IFN-gamma enhanced cytotoxicity of DC against AML cells was (33.8 +/- 1.6)% at E:T as 20:1, compared with unstimulated DC (P < 0.05); IFN-gamma up-regulated expression of costimulatory molecules of DC surface such as CD86 and CD83; after stimulation with IFN-gamma, expression of intracellular TRAIL of DC was significantly enhanced, but expression of TRAIL on cell surface of DC was low; while the significant changes of Fas L and TNF-alpha expression neither on cell surface or in cells were not observed before or after stimulation with IFN-gamma. It is concluded that DC stimulated by IFN-gamma exhibit tumoricidal activity against AML cells. The cytotoxicity is partially related to maturation of DC and TRAIL inducing apoptosis, but not associated with death domain-independent mechanism of Fas L and TNF-alpha.