Ioannis Kotsianidis1, Sotirios G. Papageorgiou2, Vassiliki Pappa2, Athanasios G. Galanopoulos3, Nora-Athina Viniou4, Theodoros P. Vassilakopoulos5, Menelaos Papoutselis1, George Vrachiolias1, Vasileios Papadopoulos1, Panagiotis T. Diamantopoulos3, Dimitris Τsokanas4, Alexandra Kourakli6 and Argiris Symeonidis6.
1 Department of Hematology, Democritus University of Thrace Medical School; Greece.
2 Second Department of Internal Medicine, Hematology Unit, Attikon University General Hospital, Athens, Greece.
3 Department of Clinical Hematology, G. Gennimatas Hospital, Athens, Greece.
4 Hematology Unit, First Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
5 Department of Hematology, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
6 Department of Internal Medicine, University Hospital of Patras, Rio, Greece.
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To the editor,
|Table1. Clinical information of 326 patients.|
|Figure 1. Overall survival at azacytidine initiation and at the time of azacytidine failure.
(A) Kaplan-Meier analysis by IPSS, IPSS-R and FPSS patient stratification at azacytidine initiation. (B) Overall survival after azacytidine failure, i) according to the post-HMA model, ii) in IPSS low/intermediate-1 risk vs all other patients and iii) in patients who continued or immediately stopped azacytidine after losing the initial response.
|Figure 2. Causes of AZA failure and their effect on outcome.
(A) Failure causes in the patient cohort (n=280). Other causes include second neoplasms, local treatment policies and inclusion in clinical trials. (B) Overall survival after AZA failure according to the reason of failure. Early death, patient’s decision and other causes were excluded from the analysis (n=225). PD: progressive disease.
|Supplementary Figure S1. Distribution of patients by the post-HMA model (n=198).
Patient disposition to the post-HMA risk categories according to their initial classification in IPSS, WPSS and IPSS-R models at AZA initiation. As expected significantly more higher-risk patients fell into the post-HMA high-risk category compared to the lower risk ones. However, these differences are not observed with FPSS.
|Supplementary Figure S2. Treatment modalities after AZA discontinuation (n=254).
(A) Treatments after AZA discontinuation (n=254). BSC: best supportive care +/- hydroxurea; IC: intensive chemotherapy; LDAC: low dose AraC, DAC: decitabine; Allo-SCT: allogeneic stem cell transplantation; AZA: retreatment with AZA after an interruption of >3 months (n=2). (B) Overall survival after AZA failure according to treatment modality. Allogeneic stem cell transplantation (Allo-SCT) and AZA retreatment were excluded from the analysis due to the very low number of cases.
|Supplementary Figure S3. Overall survival at azacytidine initiation according to WHO subtype (n=326).
Overall survival (OS) in first line azacytidine treated patients. Overlapping myeloproliferative/Myelodysplastic syndromes and CMML (collectively shown as MDS/MPN) diagnosis conferred significantly lower median OS compared to all other WHO subtypes.
RCMD = refractory cytopenia with multilineage dysplasia; RAEB = refractory anemia with excess blasts; CMML = chronic myelomonocytic leukemia; AML = acute myeloid leukemia; MDS/MPN = Myelodysplastic/myeloproliferative neoplasm.
|Supplementary Table 1. Multivariate
analysis of prognostic factors for overall survival after AZA
initiation in the whole patient cohort (n=326; 253 with full data).
|Supplementary Table 2. Multivariate
analysis of prognostic factors for overall survival after AZA failure
in patients with available post-HMA score (n=198; 194 with full data).
|Supplementary Table 3. Multivariate
analysis of prognostic factors for overall survival after loss of the
initial response to AZA (n=82; 67 with full data).
|Supplementary Table 4. Clinical information of 82 patients who relapsed after an initial response to azacytidine.|