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Evaluation of BM cytomorphology after allo-SCT in patients with MDS

Evaluation of disease status in myelodysplastic syndromes (MDS) includes assessment of blast count, dysplasia and cellularity by BM cytomorphology. In stem cell recipients with AML, we described dysplasia to be a frequent but nonspecific feature after allogeneic haematopoietic SCT on day 30 and day 100.1 Yet, we found normal cellularity by cytomorphology on day 30 to be associated with positive prognosis in these patients.1 As dysplasia and aberrant cellularity are hallmarks of MDS, we analysed the distribution and potential prognostic impact of these features by cytomorphology in BM aspirates taken on day 100 post transplant. We evaluated 25 MDS and chronic myelomonocytic leukaemia (CMML) patients (11 female, 14 male, median age 58 years, range 28–73 years) in CR at day 100 after SCT. Patients mainly suffered refractory anaemia with excess blasts-2 (RAEB-2, n=11, 44%). Mostly, they were cytogenetically favourable risk (n=19, 76%), each 3/25 patients (12%) had either an intermediate or an unfavourable karyotype according to the International Prognostic Scoring System.2 SCT was the initial therapy for 19/25 patients (76%). The most common transplantation regimen was of reduced intensity conditioning (following the European Group for Blood and Marrow Transplantation definition, n=21, 84%). Most patients were transplanted from an unrelated donor (n=21, 84%). Immunosuppression was either CYA combined with mycophenolic acid (n=17, 68%) or MTX (n=8, 32%). Acute GVHD was experienced by six patients (24%). Detailed patient, donor and transplantation characteristics are given in Table 1.

Table 1 Patient, donor and transplant characteristics

Following May Grunwald Giemsa staining, 200 nucleated cells were evaluated per BM sample. The percentage of dysplastic cells in the different haematopoietic lineages (granulopoiesis, GP; erythropoiesis, EP; megakaryopoiesis, MP) was determined.3 Furthermore, overall cellularity (discriminating increased, normal, and reduced cellularity) and cellularity in the distinct haematopoietic lineages was analysed.4

Dysplasia of 10% cells in GP was found in 11 samples (44%), in EP in 10 samples (40%) and in MP in 18 samples (72%). The median degree of dysplastic cells was 5% of cells for GP (range 0–40%), 5% for EP (0–70%) and 20% for MP (0–80%), respectively. Dysplasia (10% cells) in one lineage exclusively was found in 6 patients (24%), two lineages were affected in 3 patients (12%), and three lineages in 9 patients (36%). Data are summarized in Table 2a. Thus, there was a high frequency of dysplasia in the MDS patients’ BM samples on day 100. This was in concordance with what has been described by our group for AML patients in the post-transplant period where dysplasia had been a frequent phenomenon on day 30 and day 100.1 Interestingly, dysplasia was more frequently observed in MP than in EP or GP in this series with MDS patients. We subsequently evaluated cellularity in our MDS cohort at day 100. Overall cellularity4 was normal in only 10/25 (40%) of BM aspirates of the MDS patients. Considering the single hematopoietic lineages, normal cellularity was found in 11/25 (44%) of samples in GP, 10/25 (25%) in EP and 9/25 (36%) in MP. Overall hypocellularity was found in 11 (44%) samples (GP: n=10, 40%; EP: n=8, 32%; MP: n=11, 44%). Overall hypercellularity was observed in 4 (16%) samples (GP: n=4, 16%; EP: n=7, 28%; MP: n=5, 20%). Data are summarised in Table 2b. Thus, the majority of MDS patients showed aberrant cellularity in the BM samples on day 100 post transplant. This, too, was similar to the results in our AML cohort where aberrant cellularity was a frequent phenomenon on days 30 and 100.1

Table 2a Frequency of BM dysplasia at day 100
Table 2b Distribution of BM cellularity at day 100

After a median follow-up of 28.1 months (range 3.6–70.0 months), 5/25 (20%) patients experienced relapse with intervals ranging from 4.1 to 41.5 months after SCT. A total of 8/25 (32%) patients died within a median of 9.9 months (4.4–50.3 months). All five relapses (one refractory anaemia with complex karyotype, one RAEB-1 with an unbalanced translocation involving chromosomes 1 and 7, one RAEB-2, and two CMML with normal karyotypes) in this cohort were fatal. On day 100 (that is, before diagnosis of relapse), all five patients relapsing had <5% BM blasts. Each two patients of these had a normocellular and a hypercellular BM, and one patient showed a hypocellular BM. In this subgroup, three-lineage dysplasia (10% of cells in all three haematopoietic lineages) was a frequent finding at day 100 with 3/5 (60%) being affected. One of the five patients showed unilineage dysplasia, and the fifth patient had no significant dysplasia. In the patients remaining in stable CR, three-lineage dysplasia was observed in 6/20 patients (30%) (two-lineage dysplasia: 3/20 (15%) patients; unilineage dysplasia: 5/20 (25%); no dysplasia: 4/20 (20%), not evaluable due to marked hypocellularity: 2/20 (10%)). Thus, three-lineage dysplasia in the cohort analysed seemed more frequent in those patients who relapsed (60%) than in the patients remaining in CR (30%). This result was statistically not significant (hazard ratio (HR) 3.50, 95% confidence interval=0.46–26.32, P=0.226, logistic regression analysis).

Taken together, similar to our previous results in AML patients, aberrant cellularity and dysplasia were frequent phenomena in the post-transplant period. However, in contrast to what we reported about patients with AML on day 30 and day 100 after allogeneic SCT,1 data presented in this report lead us to hypothesize that three-lineage dysplasia (10% cells) upon BM aspiration cytomorphology on day 100 might not be nonspecific but conversely an early sign of recurrent disease in patients with MDS. These findings need confirmation in larger cohorts and might be integrated into other methods of prognostication and detection of relapse. Given an increasing incidence of MDS and increasing numbers of MDS patients treated with HSCT,5 further studies are warranted.

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Acknowledgements

We thank Waltraud Schultz and Gerlinde Finger, University of Hamburg, for expert technical assistance.

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Correspondence to U Bacher.

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TH declares part ownership of Munich Leukemia Laboratory. The other authors have no conflict of interest to declare.

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Christopeit, M., Ocheni, S., Haferlach, T. et al. Evaluation of BM cytomorphology after allo-SCT in patients with MDS. Bone Marrow Transplant 48, 465–466 (2013). https://doi.org/10.1038/bmt.2012.161

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