The ratio between CD4+ and CD8+ cells in the peripheral blood of patients with hematological malignancies is not altered by thalidomide

Thalidomide is thought to have anti-angiogenic and immunomodulatory properties, including suppression of tumor necrosis factor-alpha, effects on interleukins and interferons, down-regulation of some cell adhesion molecules, and changes in the proportion of lymphocyte subsets. It is unclear whether the clinical response to thalidomide in patients with multiple myeloma (MM), idiopathic myelofibrosis (IM), and myelodysplastic syndromes (MDS) is related to its ability to inhibit angiogenesis or its immunomodulatory effects. We examined the effect of thalidomide on T-lymphocyte subsets in 18 patients with MDS, 6 patients with MM, 4 patients with IM, and 3 patients with angioimmunoblastic lymphoma (AILD). These patients had either a relapse or progressive disease following cytotoxic chemotherapy including high-dose chemotherapy with autologous stem cell support. Thalidomide was first administered at 100 mg/day p.o. and increased to 400 mg/day. T-lymphocyte subsets (CD4 + , CD8 + ) were measured by fluorescence-activated cell sorter (FACS) before and during treatment with thalidomide. Twenty-six of 31 patients responded to thalidomide, most of them achieving partial remission. The median concentration of CD4 + cells was 443/μl, the median of CD8 + cells was 359/μl (CD3 992/μl). In our cohort, no significant changes in absolute numbers or proportions of CD3 + (P = 0.12), CD4 + (P = 0.668), or CD8 + (P = 0.143) cells were observed following the treatment with thalidomide. Although the CD4/CD8 ratio declined from 1.6 to 1.0 during 3 months of thalidomide treatment, this had no statistical significance (P = 0.1). Our findings show that an effect of thalidomide on the T lymphocytes studied is unlikely to be of major importance for the clinical effects.     

Secondary myelodysplastic syndromes following treatment with azathioprine are associated with aberrations of chromosome 7

We report 14 cases of secondary myelodysplastic syndromes (sMDS) following treatment with azathioprine for non-malignant disorders. Long-term treatment with azathioprine seems to be associated with an increased risk of MDS and subsequent leukemic transformation.     

Primary non-Hodgkin's lymphoma of bone: three cases and a short review of the literature

Primary non-Hodgkin's lymphoma of bone (PLB) is a rare entity. We present three new cases and a review of the literature. If PLB is suspected radiologically, the diagnosis must be confirmed by open biopsy. Histopathologically, PLB usually represents diffuse large B-cell lymphoma or lymphoma of the follicular center type. The extent of local disease manifestation, additional skeletal involvement, and the presence or absence of lymphadenopathy is assessed by radiological examination. Localized stages of the disease require involved-field radiotherapy (45-50 Gy) to the entire bone that is affected. Regional lymphatics must also be irradiated. Radiotherapy may be required immediately to prevent pathological fractures. In the few cases of more widespread skeletal or extraskeletal involvement, radiotherapy of the major site of manifestation may be followed by a "watch-and-wait" strategy until progression of the disease becomes apparent. In cases of intermediate or high-grade lymphoma of bone, combined radiochemotherapy is the treatment of choice for all stages. Six to eight cycles of chemotherapy (usually the CHOP regimen) are recommended for remission induction. This is followed by involved-field radiotherapy with 45-50 Gy. High-dose chemotherapy with autologous stem cell support is an option if there is no satisfactory response to conventional chemotherapy, or if early relapse occurs.     

Chronic myelomonocytic leukemia in the light of the WHO proposals

The WHO classification moved CMML to myeloproliferative/myelodysplastic disorders, and defined CMML I and CMML II according to medullary and peripheral blast count. To confirm these proposals, we analyzed 266 patients with CMML I and 73 patients with CMML II. Median survival time was 20 months for CMML I, and 15 months for CMML II (p<0.005). The cumulative risk of AML evolution differed between patient groups (p=0,001). No conclusive differences in clinical, morphologic, hematologic or cytogenetic parameters were found. These data support the WHO proposals for the classifi-cation of CMML.     

Intensive chemotherapy is not recommended for patients aged >60 years who have myelodysplastic syndromes or acute myeloid leukemia with high-risk karyotypes

BACKGROUND: It is unclear whether intensive chemotherapy is beneficial to patients with high-risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) if they are aged >/=60 years. METHODS: The authors studied 160 patients with a median age of 67 years who received intensive chemotherapy for MDS or AML with cytosine arabinoside and an anthracycline. RESULTS: At diagnosis, cytogenetic analysis was available in 146 patients. Karyotype was normal in 78 patients and abnormal in 68 patients. Of the abnormal karyotypes, 32 belonged to the high-risk category, ie, they involved either >/=3 chromosomes or chromosome 7. Complete remission (CR) was achieved by 94 patients (56%). CR rates were 70% among the patients who had a normal karyotype, 69% among the patients who had an abnormal (noncomplex) karyotype, but only 46% among the patients ho had a high-risk karyotype. The median survival was 9.5 months in the entire group, 18 months in patients with normal karyotype, 6 months in patients with abnormal, and 4 months in patients with a high-risk karyotype. A poor prognosis was attributable to low rates of CR and a high risk of early recurrence. CONCLUSIONS: According to the current data, elderly patients with AML or advanced MDS do not benefit from intensive chemotherapy if they show karyotype anomalies, especially those in the high-risk category.     

Ethik,Kommunikation und interdisziplinäre Zusammenarbeit – per Gesetz?!

Die Onkologie - Die Corona-Pandemie hat in den letzten Monaten verdeutlicht, dass das Thema Sterblichkeit trotz erheblicher Fortschritte im Bereich der Hospiz- und Palliativversorgung zu...     

The impact of age on the diagnosis and therapy of myelodysplastic syndromes: results from a retrospective multicenter analysis in Germany

Myelodysplastic syndromes (MDS) is a disease of predominantly elderly patients with a median age of >70 yrs. However, data on the management of these patients outside of clinical trials are scarce. To assess patterns of MDS management in routine patient care with regard to the impact of age, we conducted a multicenter, representative survey of MDS health services in Germany. Data of 269 patients treated at 57 institutions were collected from preplanned chart reviews and were analyzed retrospectively. At diagnosis, median age was 70 yrs, 50% of patients had a Karnofsky index (KI) of 90%, and 12% had a comorbidity index ≥ 3 according to Sorror et al. (J Clin Oncol, 25, 2007, 4246). Cytogenetic analysis and International Prognostic Scoring System (IPSS) risk assessment were performed significantly less frequently in patients >75 yrs than in patients ≤75 yrs (P < 0.001 and P = 0.019). In bivariate analysis, potential predictors for performing IPSS risk assessment were age ≤75 yrs (y/n, P = 0.019), diagnosis at a university hospital (y/n, P = 0.001), WHO subtypes RCUD (y/n, P = 0.028), RARS (y/n, P = 0.002), or RAEB II (y/n, P = 0.037). Patients ≤75 yrs were more likely to receive active therapies (i.e., chemotherapy, immunomodulatory therapy, or epigenetic therapy) than patients >75 yrs (51% vs. 37%, P = 0.007). In bivariate analysis age ≤75 yrs (y/n, P = 0.007) was a significant predictor for active treatment with no correlation with the other predictors [IPSS risk score int‐2 or high (y/n, P = 0.005), WHO subtypes RCUD (y/n, P < 0.001), RCMD (y/n, P = 0.003), RAEB II (y/n, P < 0.001), or CMML I (y/n, P = 0.020)]. This survey confirms the impact of age on the thoroughness of MDS diagnosis and the decision for active treatment. As cytogenetic analysis and risk assessment are essential for the choice of appropriate therapy, elderly patients in particular may not be receiving adequate treatment.