Hydroxyurea, one of conventional chemotherapies in chronic myelogenous leukemia(CML) and polycythemia vera, inhibits ribonucleotide reductase, which catalyzes the rate-limiting step in the de novo synthesis of deoxynucleotide triphosphates required for DNA synthesis. Various cutaneous side effects due to hydroxyurea have been reported as follows; alopecia, diffuse hyperpigmentation, scaling, poikiloderma, atrophy of the skin and subcutaneous tissues, nail changes with multiple pigmented nail bands or brittleness, erythema and scaling of acral sites simulating chronic dermatomyositis, lichen planus-like lesions, or skin tumors on the UV-light exposed areas.A 72-year-old woman, receiving hydroxyurea for CML during 5 years, revealed hydroxyurea dermopathy such as scaly papules, poikilodermatous patches, and acral ulceration, and unusually developed squamous cell carcinoma. This is a rare case of hydroxyurea dermopathy and the first case of squamous cell carcinoma by hydroxyurea in Korea.
Aged ; Alopecia ; Atrophy ; Carcinoma, Squamous Cell* ; Dermatomyositis ; DNA ; Drug Therapy ; Erythema ; Female ; Humans ; Hydroxyurea ; Hyperpigmentation ; Korea ; Lichens ; Polycythemia Vera ; Ribonucleotide Reductases ; Skin ; Subcutaneous Tissue ; Ulcer*

OBJECTIVE: To evaluate the efficacy and safety of ruxolitinib in patients with polycythemia vera (PV). METHODS: The clinical data of patients with PV treated with ruxolitinib in Peking Union Medical College Hospital from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The starting dose of oral ruxolitinib was 10 mg twice daily and could be increased after 3 months of treatment if hematocrit (HCT) control was not achieved. HCT control was defined as HCT<45% in the absence of phlebotomy. RESULTS: Thirty-three patients (17 males and 16 females) were treated with ruxolitinib at a median age of 50 (21-72) years. JAK2V617F and JAK2exon12 alleles were detected in 31 and 2 patients, respectively. Before treatment, median hemoglobin level was 187 (166-208) g/L, median white blood cell and platelet level was 10.4 (5.0-15.8)×10⁹/L and 457(237-677)×10⁹/L, respectively. Totally 17 patients (51.5%) who were resistant to or intolerant of hydroxyurea were treated with ruxolitinib as second-line therapy, and 16 patients (48.5%) were treated with ruxolitinib as first-line therapy voluntarily. The median time since PV diagnosis to treatment of ruxolitinib was 47 (3-188) months. By December 31, 2019, all the patients continued to receive ruxolitinib. The median duration of ruxolitinib exposure was 19 (2-91) months. Both in the first-line therapy group and second-line therapy group, 15 cases (accounting for 93.8% and 88.2%, respecitvely) achieved HCT control. The median time from start of therapy to HCT control was 2.2 (0.8-11.6) months. One patient (3.0%) had disease progression after HCT control. The most common hematologic adverse events included anemia and thrombocytopenia, according to CTCAE classification, including 1 case of grade 1 anemia (3.0%) and 1 case of grade 2 thrombocytopenia (3.0%). There was no thromboembolic event occurred during the therapy of ruxolitinib. CONCLUSION The remission rate of HCT in PV patients treated with ruxolitinib is high, and adverse reactions are rare. Ruxolitinib is effective in HCT control and generally well tolerated in patients with PV.
Adult ; Aged ; Anemia ; Female ; Hemoglobins/therapeutic use* ; Humans ; Hydroxyurea/therapeutic use* ; Male ; Middle Aged ; Nitriles ; Polycythemia Vera/drug therapy* ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Thrombocytopenia ; Young Adult

Hydroxyurea (HU) is an antineoplastic drug commonly used to treat chronic myeloproliferative disorders. Common dermatological side effects include hyperpigmentation, scaling, erythema, alopecia, desquamation of face and hands. Leg ulceration following HU therapy is less common and very few cases have been reported so far. Objective of this paper is to increase the awareness of hydroxyurea induced leg ulcers which will aid in the early diagnosis and appropriate treatment. The first case was a chronic myeloid leukemia (CML) patient on HU 1.5 g/day for 5 yr, who had bilateral painful perimalleolar ulcers for 6 months. The second case was a CML patient on HU 1.5 g/day for 3 yr who developed bilateral lateral malleolar ulcers. Third case was a polycythemia vera (PV) patient on HU 1 g/day for 5 yr who presented with painful medial malleolar ulcer of 2 months. The last case of our report was an elderly PV patient on HU 1.5 g/day for 2 yr and presented with lateral malleolar ulcer which persisted on reducing the dose of HU. In all the 4 cases the ulcers healed on stopping HU. Our report confirms the association of chronic hydroxyurea therapy and perimalleolar ulcers which respond promptly after discontinuation of the drug. The heightened awareness among the physicians will promote early diagnosis and prompt relief from the agonizing ulcers.
Aged ; Ankle ; Antineoplastic Agents/adverse effects/therapeutic use ; Humans ; Hydroxyurea/*adverse effects/therapeutic use ; Leg Ulcer/*chemically induced/pathology/therapy ; Leukemia, Myeloid, Chronic/drug therapy ; Male ; Middle Aged ; Phlebotomy ; Polycythemia Vera/drug therapy ; Wound Healing

To evaluate the efficacy and safety of interferon-alpha-2b (IFN-α-2b) in polycythemia vera patients(PV patient) with or without post-polycythemic myelofibrosis (post-PV MF), 30 patients with mutated JAK2V617F were enrolled in this study, from which 29 patients were evaluable. The percentage of mutated JAK2V617F allele (V617F%) was evaluated by real-time polymerase chain reaction (RT-PCR) before and after treatment with IFN-α-2b. The correlation of V617F allele burden with the major clinical outcomes was studied. Adverse effects appeared in patients was observed. The results showed that the median follow-up was 24 (12 - 42) months for 29 evaluable patients. Complete hematologic response was achieved in 10%, 48%, 72% and 78% of patients after treatment for 6, 12, 24 and 36 months respectively. The detection of V617F allele burden revealed that the molecular remission of patients (V617F%) was achieved in 41%, 76%, 89% and 89% after treatment for 6, 12, 24 and 36 months respectively. Molecular complete remission (JAK2V617F undetectable) was achieved in 4 patients, lasted from 6 to 12 months after IFN-α-2b discontinuation. The decrease of V617F% in patients with post-PV MF was significantly higher than that in patients without post-PV MF (53 ± 18% vs 32 ± 22%, respectively; p = 0.031) after treatment for 12 months. PV patients had a good tolerance to IFN-α-2b. It is concluded that IFN-α-2b can decrease the mutated V617F allele burden. Patients with PV, especially with post-PV MF, can achieve molecular remission after treatment with IFN-α-2b.
Adult ; Alleles ; Female ; Humans ; Interferon-alpha ; therapeutic use ; Janus Kinase 2 ; genetics ; Male ; Middle Aged ; Mutation ; Polycythemia Vera ; drug therapy ; genetics ; pathology ; Primary Myelofibrosis ; drug therapy ; genetics ; pathology ; Recombinant Proteins ; therapeutic use

OBJECTIVETo study the expression of bcr/abl hybridized gene in chronic myeloid leukemia (CML), acute lymphatic leukemia (ALL) and polycythemia vera (PV), and its clinical significance.

METHODSThe bcr/abl hybridized gene of interphase metaphase cells of bone marrow in 67 such patients were investigated with a probe of dual color-dual fusion translocation fluorescence in situ hybridization (D-FISH).

RESULTSIn 38 CML patients, 34 (89.5%) were positive, with one having a typical t (9; 22) at first, which changed into negative after having been treated with interferon for 38 months. In another patient, 60 days after post-allogeneic peripheral blood stem cell transplantation (PBSCT), the cytomorphology and cytogenetics were in completely remission. But 3% cells were bcr/abl positive as detected by D-FISH. Six (25%) of 24 ALL patients were positive for Bcr/abl fusion gene, which was negative in 2 PV patients. Three patients suspected of having CML were also negative and one of these three was finally diagnosed as suffering from primary thrombocythemia and one, acute myeloid leukemia (M(2a)) as detected by ETO/AML(1) gene, though the other one was still not confirmed. Two (67%) of the 3 bcr/abl negative CML patients and 5 (87%) of the 6 bcr/abl positive ALL patients had refractory leukemia.

CONCLUSIONbcr/abl hybridized gene is accurately detected by a probe of dual color-dual fusion translocation fluorescence in situ hybridization, which can serve as an effective index for clinical diagnosis, estimation of prognosis and monitor of minimal residual disease in some hematopathies.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; methods ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; physiopathology ; Male ; Middle Aged ; Polycythemia Vera ; genetics ; physiopathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; physiopathology