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V. Jachiet et al.
Management of thrombocytopenia in patients with myelodysplastic syndrome/chronic myelomonocytic leukemia-associated immune thrombocytopenia
All patients received a specific treatment for ITP, either for a platelet count <30 x 109/L without a hemorrhagic syn- drome (44%), a hemorrhagic syndrome (41%), concomi- tant antithrombotic medication or invasive procedure (10%) and associated autoimmune hemolytic anemia (5%). The response rates for each therapeutic strategy are indicat- ed in Table 2. First-line treatment consisted of glucocorti- coids and intravenous immunoglobulins (IVIg) (56%), with higher response rates to IVIg in patients with primary ITP than in those with MDS/CMML-associated ITP (90% vs. 61%, respectively, P=0.0003). ITP relapse rates after first- line therapy were significantly higher in the group with MDS/CMML-associated ITP (69% after glucocorticoids and 77% after IVIg) than in the group with primary ITP (42% after glucocorticoids and 43% after IVIg) (P=0.009). Second-line treatment consisted of a TPO-RA (68%), dana- zol (44%), rituximab (40%), dapsone (20%) or splenectomy (13%) (Online Supplementary Figure S3). The mean number of immunosuppressive treatments used in second-line ther- apy was similar in the two groups (2.1±1.5 in the group with MDS/CMML-associated ITP vs. 1.6±0.8 in the group with primary ITP; P=0.42), and approximately 40% of patients in each group received at least two different sec- ond-line treatments. The efficacy of each second-line treat- ment was comparable between the two groups, as illustrat- ed in Figure 2. In the MDS/CMML-associated ITP group, the median duration of exposure was 18 months (range, 6- 29) after rituximab, 14 months (range, 1-46) with TPO-RA, 6 months (range, 4-28) with danazol and 6 months (range, 5-6) with dapsone, with no significant differences between the durations of exposure to the different therapies.
Among the three patients with concomitant ITP and MDS/CMML treated with azacytidine (for MDS/CMML indications and two for refractory ITP), a complete hemato- logic response concomitant to the ITP complete response was noted in one patient.15
Unlike patients with primary ITP, four (10%) patients with MDS/CMML-associated ITP presented with multirefractory ITP without simultaneous progression of the underlying myelodysplasia (confirmed by bone marrow aspiration and karyotype analysis in all four refractory cases).
Outcome
The median follow-up was 66 months (range, 1-176) in the group with MDS/CMML-associated ITP, 23 months (range, 0-106) in the group with MDS/CMML without ITP and 10 months (range, 0-53) in the group with primary ITP. There was no difference in the overall survival of patients with MDS/CMML-associated ITP and those with primary ITP (log-rank test P=0.15, median overall survival not reached in any group) (Figure 3A). The leukemia-free sur- vival of patients with MDS/CMML-associated ITP was bet- ter than that of patients with MDS/CMML without ITP (log-rank test P=0.05, median leukemia-free survival not reached in any group) (Figure 3B). The four ITP patients who developed AML had CMML.
Discussion
From this multicenter study, we made the following observations: (i) patients with MDS/CMML-associated
ITP had a higher incidence of severe bleeding, despite sim- ilar platelet levels, than patients with primary ITP, which is probably explained by associated dysmegakaryopoiesis and platelet dysfunction in the former group; (ii) ITP was observed mostly in patients with low-risk MDS, accord- ing to the IPSS-R classification; (iii) the presence of a 20q deletion was more frequent among MDS/CMML patients with ITP than among those without ITP; (iv) compared to patients with primary ITP, patients with MDS/CMML- associated ITP were characterized by a lower response rate to IVIg, more frequent relapses after first-line therapy and a multirefractory profile; and (v) compared to MDS/CMML patients without ITP, patients with MDS/CMML-associated ITP did not have a worse overall survival and the risk of AML progression was low.
Up to 20% of patients with MDS or CMML experience a SAID.3 These manifestations are part of a large and het- erogeneous group of disorders. Among the various autoimmune or inflammatory disorders related to MDS/CMML, ITP is rare. Among the 61 MDS/CMML
Table 2. Treatments for immune thrombocytopenia (ITP) and response rates in patients with myelodysplastic syndrome/chronic myelomono- cytic leukemia-associated ITP and in those with primary ITP.
MDS/CMML- associated ITP n=41
41/41 (100) 40/41 (98) 18/40 (45) 19/40 (48) 3/40 (8) 23/41 (56) 7/23 (30) 7/23 (30) 9/23 (39)
25/41 (61) 17/25 (68) 13/17 (76) 3/17 (18) 1/17 (6) 11/25 (44) 5/11 (45) 1/11 (9) 5/11 (45) 10/25 (40) 3/9 (33)
Primary ITP n=75
P-value
First-line treatment, n (%)
Glucocorticoids CR
PR
NR IVIg
CR PR NR
Second-line treatment, n (%)
TPO-RA CR PR NR
Danazol CR
PR
NR Rituximab CR
PR
NR Dapsone CR
PR
NR
Splenectomy CR
PR
NR
Other treatment
Number of second-line treatments for ITP, mean (SD) Multirefractory ITP n(%)
73/75 (97) 0.30 72/73 (99) 0.69 39/67 (58) 0.19 25/67 (37) 0.30
3/67 (5) 0.52 43/73 (59) 0.77 21/39 (54) 0.08 14/39 (36) 0.67 4/39 (10) 0.01
32/75 (43) 0.06 16/32 (50) 0.18 11/15 (73) 0.86 4/15 (27) 0.56
0 0.38 4/32 (13) 0.01 3/4 (75) 0.37 0 0.65 1/4 (25) 0.54 15/32 (47) 0.61 6/9 (67) 0.19 2/9(22) 0 0.58
3/9 (33) 0.14 7/32 (22) 0.87 4/7 (57) 0.9 2/7 (29) 0.5 0 1/7(14) 0.48
4/9 (44) 5/25 (20) 2/4 (50) 2/4 (50)
4/25 (16) 1/4 (25) 1/4 (25) 2/4 (50) 5/25 (20)
2.1 (1.5) 4/41 (10)
0 0.02 - - - - - -
10/32 (31) 0.35 1.6 (0.8) 0.42
0 0.01
ITP: immune thrombocytopenia; MDS: myelodysplastic syndrome; CMML: chronic myelomonocytic leukemia; CR: complete response; PR: partial response; NR: no response; IVIg: intravenous immunoglobulin; TPO-RA: thrombopoietin receptor ago- nist; Other treatment: among vinca alkaloids, hydroxychloroquine, cyclosporine A, mycophenolate mofetil and azathioprine; SD: standard deviation.
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