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Letters to the Editor
Table 2. Treatment response and analysis of hematological response of primary autoimmune myelofibrosis after treatment (based on 2013 revised Tefferi et al.3 response criteria for myelofibrosis) (n=30)
Treatment response
Treatment line for AIMF and nature Number of cases CR CR lacking CBMB PR NR
N (%)
Global response 29 (100) 2 16 5 6
First-line therapy
GCalone
HCQalone
GC+HCQ
GC + cytoreductive agents and GF GC+IS
GC+HCQ+IS
Second-line therapy
+otherIS
Splenectomy Third-line therapy
+otherIS
Global response
Complete response
Complete response lacking CBMB Partial response
Persistent splenomegaly Persistent neutropenia Persistent anemia Persistent thrombocytopenia
No response
Not applicable because of therapeutic abstention
AIMF evolution(n=29) Stable disease Relapse
4(14) 2(7) 7(24) 1 (3) 3(10) 12(41)
29 (100)
1 0 3 0 0 0 0 5 1 0 0 0 1 2 0 0 9 1
7 (23)
0 2 1 1 0 2
1
0 1
Symptom response
2 (7) 16 (55) 5 (17) 1/5 (20) 2/5 (40) 1/5 (20) 1/5 (20) 6 (20) 1 (3)
21/29 (72%) MD/7 10/13 (77%)
23 (79%)
6 (21%)
Anemia response (hemoglobin level increase ≥ 20 g/L) Spleen response (palpable spleen becoming non-palpable) Clinical improvement (by physician’s assessment)
6(86) 0 3 2
1 (14) 0 0 1 2 (7)
2(100) 0 1 0
Hematological response N (%)
AIMF: autoimmune myelofibrosis; CR: complete response i.e., correction of cytopenia and symptoms; GC: glucocorticoids; GF: growth factors; HCQ: hydroxychloroquine; IS immunosuppressive therapy; CBMB: confirmatory bone marrow biopsy. MD: missing data.
(n=11). This is an important finding because the lack of typical JAK2, CALR and MPL mutations could be consid- ered a diagnostic criterion, and to our knowledge this is the first time that these data are available for more than 25% of cases examined. The search for clonal mutations (JAK2, CAL-R, MPL) should be mandatory with suspect- ed AIMF, and one could speculate that patients with triple negative (JAK2, CAL-R, MPL) that also have other negative clonal markers (e.g., ASXL1, spliceosome or abnormal karyotype) might in fact be misdiagnosed AIMF. However, little is known about the pathophysiol- ogy of AIMF and the possibility of a driver role of yet unknown mutations (as seen in aplastic anemia) should not be dismissed.
As reported in the literature, myelofibrosis in all 30 cases consisted of reticulin fibers, and no collagen fibrosis was described.7,8 This characteristic could also allow for differentiating AIMF from clonal processes, in parallel with the reported absence of megakaryocyte dysplasia.8,9 In Table 3 the principal differences between myeloprolif- erative disorder and AIMF are summarized to provide guidance for the diagnosis.
We used the adapted Tefferi et al. revised 2013
response criteria for myelofibrosis3 to evaluate outcome and response to therapy. These response criteria were ini- tially designed to evaluate the response to a malignant clonal disease and required a confirmatory BM biopsy to qualify for complete response (CR). Cytopenias were defined according to these criteria. Moderate, severe and deep thrombocytopenia were defined by platelet count of respectively 149–50 g/L, 49-20 g/L or <20 g/L. Moderate, severe and deep neutropenia were defined by neutrophil count of respectively 1.4–1 g/L, 0.9–0.5 g/L and <0.5 g/L. Lack of complete clinical and biological response to treatment was defined as partial response (PR) criterion. Correction of cytopenia and symptoms was defined as CR, but correction of cytopenia and symptoms without a confirmatory BM biopsy (CBMB) for correct qualification was defined as “CR lacking CBMB”.
Among the 30 cases, treatment was required because of AIMF manifestations in 29 patients and therapeutical abstention was considered for one patient. The detailed therapeutic strategy was available for all 29 treated cases. GC were prescribed as first-line therapy in 27 of 29 cases: alone in 5 of 27 and in combination with immunosup-
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