This patient has received about 12 units of sedimented red cells within 8 weeks all to no avail. The peripheral blood film showed dimorphic spectrum of normochromic and severe hypochromic red cells, leucoerythroblastosis, dysplastic myeloid series, pelger heut anomalies with myloblasts (11% of total nucleated cells).
Awaiting Immunophenotypic and Cytogenetic results.
This patient may be a candidate for azacytidine therapy. However, if the cytogenetics reveals bad prognostic marker(s), one may opt for early induction chemotherapy followed by low intensity allogeneic transplantation.
Good luck
Siva
Thank you Siva for such a thought-provoking scholarly response. MDSs, as we all know, are acquired clonal stem cell disorders which manifest heterogeneously but are unified clinically because of their tendency to progressive bone marrow failure, life-threatening infections, and transformation to acute leukemia. Sometimes, it may be difficult to differentiate MDS and Acquired Severe Aplastic Anemia (ASAA). Decision of choice of therapy of this condition could be challenging to both the physician and the patient, hence, choice of therapy is based on long-term clinical experience and critical literature review.
When I see the above case, the first thing that comes my mind is differential diagnosis of MDS, especially when the features are more in keeping with hypoplastic MDS which is the closest subtype to ASAA. You should not forget other differentials of AA such as AA/PNH syndrome, Fanconi's Anemia and Dyskeratosis Congenita which can manifest both in the young and adults with features somewhat like hypoplastic MDS and ASAA. A history of family, drug and post-hepatitis exposures could be helpful. You must look out for results of cytogenetics especially trisomy 6,8, and 13q-. Some of these abberations may connote good response to immunosuppressive therapy (IST) especially the 13q- which is a benign subset BMF responsive to IST.
For the above patient who is almost transfusion dependent, we are confronted with many challenges in diagnosis, prognostication and treatment because the management is in resource-constrained setting, where we cannot do proper cytogenetic assessment, immunophenotyping, specialized investigations and afford the azacytidine.
However, I strongly believe that azacytidine will go a long way in improving the overall survival of this patient, if opportunity is given for therapeutic trial, as previous studies have shown that it is a good IST in both high- and low-risk MDS. Twenty five and twenty-one OS have been recorded with high- and low-risk MDSs in previous studies but the secondary end-point is usually as a result of relapse to progression to BMF (ASAA), Acute Leukemia that may require different algorithm for initial management (salvage treatments), side effects of therapy or to death.
It has been observed that within 16 months of initiation of azacytidine 77% of patients have discontinued the therapy due to above relapse. I feel it could be possible to try other IST such as horse ATG plus CsA or rabbit ATG plus CsA. There could be a place for monclonal antibodies (MOAB Therapy) such as Alemtuzumab if there is a high index of suspicion of hypoplastic MDS progressing to SAA.
HSCT remains the best approach in achieving better clinical response in MDS when compared to other hypomethylating agents. This has to do with the risk assessment, age, availability of donor and other co-morbidities. However, we are relatively far from attaining this height in sub-Saharan. I believe one day we will get to this height through health globalization, equality and equity in health care.
Thanks
Collins
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