MDS Patient Research Articles

Comparison of scoring systems in primary myelodysplastic syndromes

To compare the prognostic value of scoring systems in primary myelodysplastic syndromes (pMDS), four clinicohematological systems (Rennes, Bournemouth, Düsseldorf, Pavia) and the histopathological Hannover Scoring System were applied to 415 MDS patients from the Bone Marrow Registry of Hannover Medical School. According to the FAB classification, 180 patients (43%) were diagnosed as RA, 33 (8%) as RARS, 99 (24%) as RAEB, 36 (9%) as RAEBt, and 48 (12%) as CMMOL; 19 patients (4%) were not further classified (MDS.UC). All scoring systems revealed three or four groups of patients with significantly different survival times. The ranges and standard deviations in these groups were similar but high in all scoring systems. A good differentiation between short-term survivors (< 1 year survival time) and intermediate-term survivors (1-4 years) was possible with all tested scoring systems, but the differentiation between intermediate- and long-term survivors (> 4 years) was not distinctive enough. The problem of risk assessment in the single patient is furthermore elucidated by the values of specificity and sensitivity, which were relatively low in all scoring systems tested. Best results were yielded by the Bournemouth Score for long-term survivors and the Düsseldorf and Hannover Score for intermediate- and short-term survivors. Multivariate analysis of all parameters used in the scoring systems showed the highest negative impact on survival for increase of myeloblasts, anemia, myelofibrosis, high age of the patient, and abnormal localization of immature precursors (ALIPs). Therefore, the histopathological Hannover Scoring System is not only equal to clinicohematological risk assessment in pMDS, but also includes important independent prognostic parameters. Risk assessment for the individual low-risk MDS patient using only initial parameters may be rendered impossible due to the biological nature of pMDS. Therefore, sequential analysis is needed to elucidate random events which alter the prognosis.

Immunoglobulin and T-cell receptor delta gene rearrangements are rarely found in myelodysplastic syndromes in chronic phase

Clonality, in MDS, can only be assessed in patients with chromosomal rearrangements or in females heterozygote for X chromosome restricted polymorphisms. “Illegitimate” rearrangements of the immunoglobulin heavy chain (Ig H) gene and incomplete rearrangements involving Vδ 2 and Dδ 3 segments of the T-cell receptor delta (TcR δ) gene are seen in some cases of AML, and AML post-SMD, and can be detected by a sensitive PCR method. In order to analyse clonality in additional cases in MDS, we looked for Ig H and TCR δ gene rearrangement by PCR in 95 cases of MDS. A rearrangement of the Ig H gene was seen in 2 of the 95 patients: in the circulating blood of 2 of the 36 cases of chronic myelomonocytic leukaemia (CMML) and in none of the marrow samples of the other 59 MDS. A rearrangement of the TcR δ gene (involving Vδ 2 and Dδ 3 segments) was seen in three cases (in the circulating blood of two other CMLL patients, and in the bone marrow of another MDS patient). Twenty-five of the 90 case of MDS with negative PCR findings, in addition to the five cases with positive PCR findings underwent Southern blot analysis of Ig H and TcR δ genes, and PCR analysis of Vδ 1 and Jδ 1 segments of the TcR δ gene. Those examinations were normal in all the cases tested. In patients with positive PCR findings for Ig H or Vδ 2 Dδ 3 rearrangements, the proportion of rearranged cells was evaluated at 1–5% in four cases, and 5–10% in the remaining patient. Because the analysis was performed on total circulating leukocytes or total nucleated marrow cells, the nature of the clonal population in positive cases (lymphoid cells ? myeloid cells ? blasts ?) could not be determined. From a practical point of view, Ig H and TcR δ gene rearrangements seem to very rare in MDS, and cannot be used as clonality markers in most cases.

The erythropoietin receptor gene in myelodysplastic syndromes and other stem cell disorders: A different gene in an MDS patient

Secondary AML (sAML), referring to AML arising after prior cytotoxic/radiation/immunosuppressive therapy (tAML) or an antecedent hematologic disorder, now primarily classified as AML with myelodysplasia-related changes (AML-MRC), accounts for 10%–30% of AML cases and is associated with a poor prognosis. sAML has historically been treated with intensive chemotherapy (eg, 7 + 3) or less aggressive regimens (eg, low-dose cytarabine or azacytidine for older/unfit patients); however, outcomes are typically poor, especially for older adults. Recently, CPX-351, a liposomal co-encapsulation of cytarabine and daunorubicin at a synergistic ratio, demonstrated improved front-line outcomes in older patients with high-risk/sAML. CPX-351 has been approved for adults with newly diagnosed tAML or AML-MRC and has an NCCN category 1 recommendation for induction therapy of patients aged >60 years with high-risk/sAML. Other novel therapies may also benefit certain sAML subgroups. Greater clarity around the optimal diagnosis and treatment of sAML patients is needed to improve outcomes in this high-risk subpopulation.

ＨＰＡ‐５ｂ（Ｂｒ‐ａ）抗原感作による血小板輸血不応例

A 65-year-old female MDS patient Y. M showed refractoriness to transfusions of HLA-matched platelets in 4 out of 72 occasions. Analysis of Y. M serum by a monoclonal antibody specific immobilization of platelet antigens (MAIPA) assay revealed that the serum contained anti-HPA-5b antibody directed against an epitope on platelet glycoprotein (GP) Ia/IIa. The Y. M serum was tested for its reactivity against ineffective as well as effective platelets by MAIPA assay. The serum was reactive to the platelet antigen against an epitope on GP Ia/IIa of ineffective platelets, but not against an epitope on GP IIb/IIIa, GPIb or GPIV. The serum was not reactive to any of GPs of effective platelets. Platelet typing of patient Y. M and four ineffective HLA-matched donors showed that patient Y. M was HPA-5a/a, whereas four ineffective donors were HPA-5a/b. The results indicate that HPA-5 antigen is responsible for the refractoriness to the platelet transfusion.