tretinoin and Primary-Myelofibrosis

Acute promyelocytic leukemia (APL) with myelofibrosis (MF) is rare, and only 14 cases have been reported in the literature to date.. A 42-year-old woman was admitted to the hospital with easy bruising and excessive bleeding. With the remission of the primary disease during treatment, the degree of fibrosis did not decrease, but worsened progressively.. The woman was diagnosed with acute promyelocytic leukemia with secondary myelofibrosis.. All-trans retinoic acid (ATRA) was discontinued after 6 months of complete remission of APL. Arsenic trioxide (ATO) was discontinued because of supraventricular tachycardia 9 months after complete remission of APL.. After withdrawal of ATRA for 2 months, the degree of fibrosis was significantly alleviated, and after withdrawal of ATRA for 8 months and ATO for 5 months, bone marrow biopsy showed no reticular fiber deposition.. In this case report and review of an additional 14 cases of APL with MF, we highlighted the importance of the degree of MF to be evaluated by bone marrow biopsy at the time of bone marrow aspiration when APL is suspected. If MF is present, the type of MF should be determined in a timely manner, and appropriate intervention measures should be taken accordingly.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Female; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Primary Myelofibrosis; Treatment Outcome; Tretinoin

Primary myelofibrosis (PMF) is a type of cloned myeloproliferative neoplasm stemming from haematopoietic stem cells, and tends to transform to acute myeloid leukaemia (AML) in approximately 10-20% of cases over a 10-year period. The transformation into AML has a poor prognosis, with a median overall survival of only 2.6 months in patients receiving supportive treatment. To date, treatment of AML transformation remains poor. The case of a 58-year-old female patient with AML transformed from PMF, who was treated with decitabine combined with all-trans retinoic acid, is reported. The patient had complete remission and a 17-month overall survival from initial diagnosis of transformed AML, with tolerated haematologic toxicity during the treatment period.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Transformation, Neoplastic; Decitabine; Female; Humans; Leukemia, Myeloid, Acute; Middle Aged; Primary Myelofibrosis; Prognosis; Tretinoin

Topics: Acute Disease; Adenocarcinoma; Antineoplastic Agents; Capecitabine; Chemoradiotherapy; Colorectal Neoplasms; Female; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Middle Aged; Neoplasms, Second Primary; Organoplatinum Compounds; Oxaliplatin; Pancytopenia; Primary Myelofibrosis; Remission Induction; Tretinoin

Differentiation therapy has emerged as a powerful way to target specific hematologic malignancies. One of the best examples is the use of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), which has significantly improved the outcome for patients with this specific form of acute myeloid leukemia (AML). In considering how differentiation therapy could be used in other forms of AML, we predicted that compounds that induce terminal differentiation of megakaryocytes would be effective therapies for the megakaryocytic form of AML, named acute megakaryocytic leukemia (AMKL). We also speculated that such agents would reduce the burden of abnormal hematopoietic cells in primary myelofibrosis and alter the differentiation of megakaryocytes in myelodysplastic syndromes. Using a high-throughput chemical screening approach, we identified small molecules that promoted many features of terminal megakaryocyte differentiation, including the induction of polyploidization, the process by which cells accumulate DNA to 32N or greater. As the induction of polyploidization is an irreversible process, cells that enter this form of the cell cycle do not divide again. Thus, this would be an effective way to reduce the tumor burden. Clinical studies with polyploidy inducers, such as aurora kinase A inhibitors, are under way for a wide variety of malignancies, whereas trials specifically for AMKL and PMF are in development. This novel form of differentiation therapy may be clinically available in the not-too-distant future. Clin Cancer Res; 19(22); 6084-8. ©2013 AACR.

Topics: Antineoplastic Agents; Aurora Kinase A; Azepines; Cell Differentiation; Cell Line, Tumor; Humans; Leukemia, Megakaryoblastic, Acute; Leukemia, Promyelocytic, Acute; Megakaryocytes; Mitosis; Polyploidy; Primary Myelofibrosis; Protein Kinase Inhibitors; Pyrimidines; Tretinoin

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Consolidation Chemotherapy; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Promyelocytic, Acute; Oxides; Primary Myelofibrosis; Remission Induction; Survivors; Tretinoin

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Primary Myelofibrosis; Prognosis; Reticulin; Tretinoin

In 11/13 acute promyelocytic leukaemia (APL) cases treated with tretinoin (RA) we observed RA-induced inaspirable collagenous fibrosis of the bone marrow. To study the mechanism of RA on collagen production, we cultured a human bone marrow derived stromal cell line and an osteoblastic cell line with RA in vitro. 10(-7) and 10(-6)M of RA stimulated collagen production. Clinical and experimental observation may be important to understand this adverse effect of RA as it is useful in cancer chemoprevention as well as treatment for APL. This adverse effect is spontaneously reversible after stopping RA or following chemotherapy.

Topics: Adult; Aged; Bone Marrow; Cell Line; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Primary Myelofibrosis; Tretinoin