Alfa-interferon in the treatment of essential thrombocythemia: clinical results and evaluation of its biological effects on the hematopoietic neoplastic clone. Italian Cooperative Group on ET.
The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET) patients has been reported by several authors. The aim of this study is to assess the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December 1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months. Ten of 11 obtained complete hematological remission (CHR) and one achieved partial hematological remission. Megakaryocyte concentration was reduced in six cases. The spleen,which was enlarged in four patients, decreased in size in two patients. Seven of eight patients who were symptomatic at diagnosis obtained resolution of symptoms. In order to obtain indications about the structural modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform infra-red microspectroscopy analysis performed on 10 single Mks of each patient, was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic components absorption) in five cases, and in three of these five patients A1/A2 ratios achieved normal values. After alfa-IFN treatment we did not observe any change in the methylation pattern of DNA from the granulocyte fraction. Our results confirm the efficacy of alfa-IFN in ET patients, and the decrease of A1/A2 ratios in several patients is a demonstration of the depth of the effect of alfa-IFN on the neoplastic clone. The results of clonality studies showed the persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis remains to be determined and should be explored in future clinical trials.
Sacchi
S
S
Dipartimento di Scienze Mediche, Radiologiche ed Oncologiche, Università di Modena, Italy.
Gugliotta
L
L
Papineschi
F
F
Liberati
A M
AM
Rupoli
S
S
Delfini
C
C
Ruggeri
M
M
Cavanna
L
L
Bucalossi
A
A
Benedetti
E
E
Ferrandina
C
C
Vinci
G
G
Morselli
M
M
Torelli
G
G
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D004247:DNA / Q000097:blood; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count; D008533:Megakaryocytes / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D010735:Phosphoglycerate Kinase / Q000235:genetics; D010976:Platelet Count; D012150:Polymorphism, Restriction Fragment Length; D013163:Splenomegaly / Q000628:therapy; D013922:Thrombocytosis / Q000097:blood / Q000628:therapy*; D014960:X Chromosome
D016898:Interferon-alpha; D004247:DNA; D010735:Phosphoglycerate Kinase