Annals of Hematology

The management of aplastic anemia continues to challenge clinical investigators. With bone marrow transplantation or immunosuppression the prognosis of the patient with aplastic anemia has improved remarkably. For patients who are not eligible for bone marrow transplantation, antilymphocyte globulin has become the standard treatment. There is growing evidence that some patients also respond to immunosuppression with cyclosporin A. Further data suggest that combination of cyclosporin A with antilymphocyte globulin or androgens might be beneficial. An international workshop summarized the data on cyclosporin A treatment in aplastic anemia and attempted to create guidelines for the use of cyclosporin A in the management of aplastic anemia.

Một chất ức chế phân tử nhỏ mới, 4-(3-methoxy-phenylsulfannyl)-7-nitro-benzofurazan-3-oxide (MNB), cạnh tranh với peptide Bak BH3 để gắn vào protein Bcl-2 với độ ái lực gắn kết IC50 = 0.70 μM, được đánh giá bằng cách thử nghiệm gắn kết dựa trên phân cực huỳnh quang. Tế bào HL-60 có mức độ biểu hiện Bcl-2 cao nhất trong số các dòng tế bào được kiểm tra. Khi được điều trị với 5 μM MNB trong 6 giờ, 85% tế bào HL-60 đã được phát hiện là trải qua hiện tượng apoptosis. Chất ức chế pan-caspase, Z-VAD-FMK, ngăn chặn hiện tượng apoptosis do MNB gây ra trong tế bào HL-60. Sự hoạt hóa của các caspase-2, caspase-3, caspase-7, caspase-8, caspase-9 và PARP đã được quan sát thấy từ sớm, từ 4 đến 6 giờ điều trị MNB. Ngoài ra, đã được xác nhận rằng chất ức chế đặc hiệu caspase-3, Z-DEVD-FMK, ngăn chặn sự hoạt hóa của caspase-8 trong tế bào HL-60 được điều trị bằng MNB. Điều trị bằng MNB không làm thay đổi mức độ biểu hiện Bcl-2 hoặc Bax trong tế bào HL-60, nhưng gây ra sự cắt ngang của Bid. Các thí nghiệm tiếp theo đã chứng minh rằng MNB ức chế sự hợp dimer của Bcl-2 với Bax hoặc Bid, giảm tiềm năng màng ty thể (ΔΨmt), và gây ra sự phóng thích cytochrome c từ ty thể trong tế bào HL-60. Những kết quả này gợi ý rằng MNB gây ra hiện tượng apoptosis trong HL-60 bằng cách ức chế sự hợp dimer của Bcl-2 với các thành viên Bcl-2 thúc đẩy apoptosis, dẫn đến việc giảm tiềm năng màng ty thể và sự phóng thích cytochrome c, sự hoạt hóa của các caspase và PARP; đây là một quá trình phụ thuộc vào caspase mà trong đó sự hoạt hóa của caspase-8 phụ thuộc vào con đường truyền tín hiệu apoptosis của ty thể. MNB kéo dài tuổi thọ cho chuột mang HL-60, giết chết mạnh mẽ các tế bào AML và ALL tươi, chỉ ra rằng nó có tiềm năng được phát triển để điều trị bệnh bạch cầu.

To evaluate the strategy of using high-dose etoposide mobilization followed by autologous peripheral blood stem cell transplantation (APBSCT) in patients with diffuse large B cell lymphoma (DLBCL) refractory to rituximab-based chemotherapy. Forty patients with refractory DLBCL were treated with high-dose etoposide for stem cell mobilization. All patients were in progressive disease (PD) prior to mobilization and underwent high-dose chemotherapy followed by APBSCT. Successful PBSC mobilization was achieved in all patients. Twenty-three patients (57.5%) showed a clinical response to high-dose etoposide. After APBSCT, 17 patients (42.5%) achieved CR. The 2-year progression-free (PFS) and overall survival (OS) rate were higher in patients responding to high-dose etoposide (64.1% and 77.7%) compared to those without response (11.8% and 11.8%; P < 0.001 for both). The response to high-dose etoposide mobilization therapy was an independent prognostic factor for CR achievement, PFS and OS after APBSCT. High-dose etoposide mobilization chemotherapy followed by APBSCT could rescue a proportion of patients with refractory DLBCL who responded to etoposide mobilization regimen.

A patient who had been admitted to hospital for surgical treatment of inguinal hernias was found to have a blood group phenotype of A1B in the presence of a non-auto-anti-B. No previous records of the patient's blood group were available. The serological workup including absorption and saliva inhibiton studies yielded a high probability for an acquired B-antigen which is known to be often associated with carcinoma of the colon. Subsequent coloscopy revealed the presence of a carcinoma of the sigmoid, unaccessable to palpation. To our knowledge this is the first report in the literature that the serological diagnosis of an acquired B-antigen led to the detection of a hitherto undetected carcinoma.

Inherited deletions of α-globin genes and/or their upstream regulatory elements (MCSs) give rise to α-thalassemia, an autosomal recessive microcytic hypochromic anemia. In this study, multiplex ligation-dependent probe amplification performed with commercial and synthetic engineered probes, Gap-PCR, and DNA sequencing were used to characterize lesions in the sub-telomeric region of the short arm of chromosome 16, possibly explaining the α-thalassemia/HbH disease phenotype in ten patients. We have found six different deletions, in heterozygosity, ranging from approximately 3.3 to 323 kb, two of them not previously described. The deletions fall into two categories: one includes deletions which totally remove the α-globin gene cluster, whereas the other includes deletions removing only the distal regulatory elements and keeping the α-globin genes structurally intact. An indel was observed in one patient involving the loss of the MCS-R2 and the insertion of 39 bp originated from a complex rearrangement spanning the deletion breakpoints. Finally, in another case, no α-globin gene cluster deletion was found and the patient revealed to be a very unusual case of acquired α-thalassemia-myelodysplastic syndrome. This study further illustrates the diversity of genomic lesions and underlying molecular mechanisms leading to α-thalassemia.

Repeated courses of HD IVIg are reported to induce stable remission in a significant proportion of adults with chronic refractory ITP. We have treated 14 such patients obtaining a remission rate quite comparable to the 5–10% of spontaneous remission.

We studied the distribution of ABO blood groups in Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, acute myeloid leukaemia and acute lymphoblastic leukaemia, in children up to the age of 12 years, in a hospital-based retrospective study. Blood group data were recorded from the case records of all the patients in a tertiary care centre with the diagnosis of Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, acute myeloid leukaemia and acute lymphoblastic leukaemia, during the period 1987–1997. There were 63 Hodgkin’s lymphoma, 78 non-Hodgkin’s lymphoma, 116 acute myeloid leukaemia and 522 acute lymphoblastic leukaemia patients. We assessed the distribution of ABO blood groups and the difference in the distribution from the source population. In Hodgkin’s lymphoma, there were 45.6% [95% confidence interval (CI): 6.8–84.5] more patients with B blood group. In acute lymphoblastic leukaemia, there were 14.3% (95% CI: 3.2–25.2) more patients with O blood group. In Hodgkin’s lymphoma and non-Hodgkin’s lymphoma patients, there were 56.5% (95% CI: 19.9–85.4) and 52.9% (95% CI: 18.1–82.6) less patients with A blood group, respectively. This shows that the relationship between the ABO blood groups and haematological malignancies merits further investigation in a population-based prospective study. This is the first study of its kind in any Indian population.

The objective of this study was to compare health-related quality of life (HRQOL) between diffuse large B cell lymphoma (DLBCL) survivors of different age categories (18–59/60–75/76–85 years) and to compare their HRQOL with an age- and sex-matched normative population. The population-based Eindhoven Cancer Registry was used to select all patients diagnosed with DLBCL from 1999 to 2010. Patients (n = 363) were invited to complete the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, and 307 survivors responded (85 %). Data from an age- and sex-matched normative population (n = 596) were used for comparison. DLBCL survivors aged 18–59 years scored better on physical functioning, quality of life, appetite loss and constipation than survivors of 76–85 years old (all p < 0.05). Financial problems more often occurred in survivors aged 18–59 years compared to survivors of 76–85 years old (p < 0.01). Compared to the normative population, DLBCL survivors aged 18–59 years showed worse scores on cognitive and social functioning and on dyspnea and financial problems (p < 0.01, large- and medium-size effects). In survivors of the other age categories, only differences with trivial or small-size effects were found. Although younger DLBCL survivors have better HRQOL than older survivors, the differences found between younger survivors and normative population were the largest. This suggests that having DLBCL has a greater impact on younger than older survivors and that the worse HRQOL observed in older DLBCL survivors in comparison with younger survivors is caused mostly by age itself and not by the disease.