Modulation of bone marrow microenvironment following ruxolitinib therapy in myelofibrosis

Figures & data

Table I. Characteristics of 10 patients with MF treated with ruxolitinib.

Pts	Treatment before rxt	Months of rxt therapy	Mutation	Spleen Reduction (%)	Weight gain (Kg)	Marrow cellularity (%)		Marrow fibrosis (WHO grade)		Megakaryocyte atypia		Megakaryocyte proliferation		Sinusoidal dilatation		Sinusoidal density
						BL	Post rxt	BL	Post rxt	BL	Post rxt	BL	Post rxt	BL	Post rxt	BL	Post rxt
						1	hydroxyurea	36	JAK2^V617F	20	7	100	40	3	3	++	–	+++	+	–	+	+	++
2	hydroxyurea	36	JAK2^V617F	30	8	80	50	2	2	++	+	+++	+	+	+	++	++
3	hydroxyurea	35	JAK2^V617F	65	11	70	40	2	2	+	–	++	+	–	+	+	++
4	—	27	MPL	100	5	50	70	3	2	+	+	++	+	–	+	+	+
5	—	24	JAK2^V617F	NA	12	90	70	2	2	–	+	+++	+	–	+	+	++
6	—	14	JAK2^V617F	100	14	90	70	3	2	+	–	+++	+	–	+	+++	+++
7	hydroxyurea	12	CALR	35	4	10	10	3	3	+	+	+	+	–	+	+	++
8	danazol  pipobroman	12	Triple neg	100	11	90	70	2	1	+	–	++	++	–	+	+	+++
9	hydroxyurea	40	CALR	20	5	10	10	3	3	–	–	+	+	+	+	+	++
10	hydroxyurea	40	JAK2^V617F	100	3	90	70	2	2	++	–	+++	+	–	+	+	++

Marrow trephines were evaluated for cellularity (%); megakaryocyte proliferation [3-point scoring system based on the number of megakaryocytes: < 10 (+); between 10–20 (++) and >20 (+++) at 200× magnification]; clustering and atypia [3-point scoring system ranging from normal (–), through rare dense clustering and moderate atypia (+) to dense clustering of megakaryocytes with aberrant nuclear/cytoplasmic ratio and hyperchromatic and irregularly folded nuclei (++)] [14]; sinusoidal density [3-point scoring system based on the number of sinusoids (< 20 (+); between 20–30 (++) and >30 (+++) at 200× magnification) [15]] and luminal dilatation [2-point scoring system based on absence (–) or presence (+)]; marrow fibrosis according to WHO criteria [16].

BL, baseline; Post rxt, post-ruxolitinib treatment.

Figure 1. Increased sinusoidal dilatation after ruxolitinib treatment. Anti CD-34 immunohistochemical staining, 200× magnification. Patients 5 and 7 at baseline (a, c) and after 24 and 12 months of treatment, respectively (b, d). In these patients, fibrosis and cellularity remained stable [Table I].

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