tretinoin and Sarcoma--Myeloid

We report here the first case of NPM1/RARA-positive acute promyelocytic leukemia (APL) preceded by myeloid sarcoma (MS) in the vertebra. A 52-year-old man was diagnosed with MS, as the tumor cells were positive for myeloperoxidase and CD68 but negative for CD163. After treatment with steroids and radiation, the size of the tumor was markedly reduced and peripheral blood count was normal. Bone marrow examination showed 89.2% consisted of unclassified promyelocytes characterized by round nuclei and abundant small azurophilic granules but no Auer rods. The results of chromosome analysis showed 46,XY,t(5;17)(q35;q12). Reverse-transcription polymerase chain reaction amplified the NPM1/RARA fusion transcripts derived from a combination of NPM1 exon 4 and RARA exon 5, or of NPM1 exon 1 and RARA exon 5; the latter of these has not been reported previously. Electron microscopic examination of the promyelocyte nuclei showed they were oval with mild nuclear chromatin condensation and small- to medium-sized nucleoli. Hematological and molecular complete remission was attained after induction therapy including all-trans retinoic acid. As MS was also diagnosed in two of the seven other reported cases of APL with NPM1/RARA, MS may occur more frequently in APL with NPM1/RARA than APL with PML/RARA.

Topics: Cell Nucleolus; Cell Nucleus; Chromatin; Exons; Gene Fusion; Granulocyte Precursor Cells; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Magnetic Resonance Imaging; Male; Microscopy, Electron; Middle Aged; Nuclear Proteins; Nucleophosmin; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Myeloid; Tretinoin

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Cranial Irradiation; Daunorubicin; Ear Neoplasms; Humans; Injections, Spinal; Leukemia, Myelomonocytic, Acute; Male; Oxides; Radiography; Remission Induction; Sarcoma, Myeloid; Tretinoin

Acute promyelocytic leukemia (APL) has become a curable disease by all-trans retinoic acid (ATRA)-based induction therapy followed by two or three courses of consolidation chemotherapy. Currently around 90% of newly diagnosed patients with APL achieve complete remission (CR) and over 70% of patients are curable. To further increase the CR and cure rates, detection and diagnosis of this disease at its early stage is very important, hopefully before the appearance of APL-associated coagulopathy. In induction therapy, concomitant chemotherapy is indispensable, except for patients with low initial leukocyte counts. Prophylactic use of intrathecal methotrexate and cytarabine should be done, particularly for patients with hyperleukocytosis. If patients relapse hematologically or even molecularly, arsenic trioxide will be the treatment of choice under careful electrocardiogram monitoring. Am80, liposomal ATRA, gemtuzumab ozogamicin or ATRA in combination with cytotoxic drugs may be used at this stage or later. Allogeneic SCT will be the treatment of choice after patients of age <50 years have relapsed, provided that they have HLA-identical family donors or DNA-identical unrelated donors.

Topics: Antineoplastic Agents; Humans; Leukemia, Promyelocytic, Acute; Remission Induction; Sarcoma, Myeloid; Treatment Outcome; Tretinoin

Topics: Adult; Antineoplastic Agents; Arsenic Trioxide; Humans; Kidney Transplantation; Male; Renal Insufficiency, Chronic; Sarcoma, Myeloid; Tissue Donors; Transplant Recipients; Tretinoin

Granulocytic sarcoma (GS) is an extramedullary myeloid tumor composed of immature cells of the granulocytic series. It rarely occurs in acute promyelocytic leukemia (APL). No case of long-term survival in an APL patient with recurrent GS has been reported.. A 54-year-old female patient was diagnosed with APL in 1995 and has been in complete remission (CR) of bone marrow morphology for 24 years; however, recurrent GS occurred successively in ovary, breast, spine, body of sternum, lymph nodes, soft tissues from 2004 to 2019.. The immunohistochemistry confirmed the diagnosis of GS, and fluorescence in situ hybridization (FISH) revealed its origin from APL.. She received surgery, and had an excellent response to all-trans retinoic acid (ATRA), DA (daunorubicin combined with cytarabine) regimens, and arsenic trioxide (ATO).. The patient achieved CR in March 2020 after radiotherapy followed by ATO and ATRA. So far, she is still in follow-up.. It is rare that recurrent GS at multiple sites is involved in APL patient with bone marrow morphology in CR. It is interesting to observe a long-term excellent response to ATRA, chemotherapy and ATO. Although multiple recurrence of GS in patients with APL is rare, the data in this case highlight the need for individualized treatment when such conditions occur.

Topics: Female; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Remission Induction; Sarcoma, Myeloid; Tretinoin

Topics: Arsenic Trioxide; Ear Canal; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Recurrence; Sarcoma, Myeloid; Tretinoin

Acute promyelocytic leukemia (APL) is a curable subtype of acute myeloid leukemia. APL is currently treated with combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) resulting in the induction of apoptosis and differentiation of the leukemic cells. Differentiation syndrome (so-called ATRA syndrome) is the main life-threatening complication of induction therapy with these differentiating agents.. Herein, we report the case of a 49-year-old woman diagnosed with APL with, concomitantly, a bulky cutaneous lesion of 10 cm diameter with a red-to-purple background and a necrotic center, localized on her abdomen.. After 10 days of treatment, the cutaneous lesion became purulent. Fluorescence in situ hybridization (FISH) analysis performed on this pus confirmed the presence of malignant features in the involved granulocytes proving their origin from the differentiation of leukemic APL cells, as all the analyzed nuclei showed 2 promyelocytic leukemia (PML)-retinoic acid receptor-a (RARA) fusions signals.. The association by ATRA and ATO was continued.. Eventually, the evolution was favorable with healing in three weeks.. This case report therefore highlights the differentiation phenomenon of promyelocytic blasts within promyelocytic sarcoma with the ATRA-ATO combination and the efficacy of this drug association in resolving both the malignant sarcoma and a secondary local infection.

Topics: Abdomen; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Cell Differentiation; Female; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Middle Aged; Oxides; Sarcoma, Myeloid; Suppuration; Tretinoin

Extramedullary relapse is a rare phenomenon in patients with acute promyelocytic leukemia (APL), especially that derived from urogenital systems like the testicles. In this report, we describe an APL patient who had received standard induction/maintenance therapy resulting in durable remission for 4.5 years, when he presented with a unilateral testicular mass confirmed as myeloid sarcoma; this was followed by systemic relapse of APL. Retrospective analysis of the involved blood and bone marrow samples at the time of the initial diagnosis revealed a rare point mutation of FLT3-TKD and a novel mutation of WT1. These mutations were detected recurrently throughout the course of the disease. After reinduction therapy with arsenic trioxide and all-trans retinoic acid combined with daunorubicin, complete hematological remission was achieved for the ensuing salvage allogeneic hematopoietic stem cell transplant.

Topics: Adult; Arsenic Trioxide; Arsenicals; Combined Modality Therapy; Daunorubicin; fms-Like Tyrosine Kinase 3; Humans; Leukemia, Promyelocytic, Acute; Male; Neoplasm Recurrence, Local; Oxides; Salvage Therapy; Sarcoma, Myeloid; Testicular Neoplasms; Testis; Tretinoin; WT1 Proteins

Acute promyelocytic leukemia (APL) is a malignant subtype of acute myeloid leukemia caused by the PML-retinoic acid receptor (RAR)α fusion gene. APL may be discovered in adulthood and diagnosed after spontaneous gingival bleeding or difficulty in hemostasis after oral surgery such as tooth extraction. However, APL is extremely rare in children.. A 1-year-old boy presented with a mass on the mentum of the mandible. The marked periosteal reaction was seen on CT and MRI, leading to strong suspicion of a malignant bone-derived tumor such as a sarcoma. Chromosome banding by fluorescence in situ hybridization (FISH) showed PML-RARα, confirming the diagnosis of APL. Treatment with tretinoin was immediately initiated. No signs of recurrence have been noted 1 year after treatment.. We report herein a rare case involving an infant with APL who presented with an extramedullary tumor of the mandible, whom we treated with good results.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Diagnosis, Differential; Flow Cytometry; Follow-Up Studies; Humans; Immunohistochemistry; Infant; Leukemia, Promyelocytic, Acute; Magnetic Resonance Imaging; Male; Mandibular Neoplasms; Photomicrography; Rare Diseases; Risk Assessment; Sarcoma, Myeloid; Tomography, X-Ray Computed; Treatment Outcome; Tretinoin

Topics: Adult; Aminoglycosides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Benzoates; Bone Marrow; Bone Neoplasms; Combined Modality Therapy; Doxorubicin; Drug Resistance, Neoplasm; Gemtuzumab; Hematopoietic Stem Cell Transplantation; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Male; Mercaptopurine; Methotrexate; Oxides; Radionuclide Imaging; Remission Induction; Salvage Therapy; Sarcoma, Myeloid; Soft Tissue Neoplasms; Tetrahydronaphthalenes; Tretinoin

Central nervous system (CNS) involvement is rarely observed in acute promyelocytic leukemia (APML). Most cases of CNS involvement occur at relapse rather than at presentation. Because of the extremely low incidence of CNS disease, diagnostic lumbar puncture is not routinely required and prophylactic intrathecal chemotherapy is not routinely administered. Here, we describe a teenage patient with newly diagnosed APML, chloromas, and symptomatic CNS involvement confirmed by MRI and cerebrospinal fluid (CSF) findings.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Neoplasms; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Humans; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Mercaptopurine; Methotrexate; Oncogene Proteins, Fusion; Radiotherapy; Sarcoma, Myeloid; Tretinoin

Granulocytic sarcoma (GS) is a localized tumor composed of immature myeloid cells. This extramedullary tumor can present before, concurrent with or after the diagnosis of acute myeloid leukemia. GS is extremely uncommon in acute promyelocytic leukemia (APL). As a proportion of patients never develop systemic disease, correct and timely diagnosis may be rather difficult, but is a prerequisite for optimal outcome. GS should be considered in the differential diagnosis of children with unusual bone lesions. We describe a patient with GS who presented with symptoms mimicking osteomyelytis or rheumatoid disease.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Arthritis, Psoriatic; Biomarkers, Tumor; Diagnostic Errors; Female; Humans; Leukemia, Promyelocytic, Acute; Oncogene Proteins, Fusion; Osteolysis; Osteomyelitis; Remission Induction; Sarcoma, Myeloid; Shoulder Pain; Tretinoin

Topics: Adult; Antibiotics, Antineoplastic; False Positive Reactions; Hip; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Recurrence; Sarcoma, Myeloid; Tretinoin

Isolated extramedullary relapse is rare in patients with acute promyelocytic leukemia (APL) after allogeneic stem cell transplantation (SCT), and an optimal therapy for it has not been established. We describe a patient with APL who developed serially occurring extramedullary disease (EMD) after SCT. We confirmed that EMD had arisen from the recipient's APL blasts by detecting t(15;17) and PML/RARalpha from the tumor cell suspension. The patient displayed EMD 4 times at different sites. Administration of all-trans retinoic acid with local radiotherapy and with chemotherapy for the first to third EMDs resulted in regression of the tumors. However, these regimens did not prevent the subsequent occurrence of new EMD. For the fourth EMD, intravenous administration of arsenic trioxide followed by local radiotherapy resulted in the disappearance of EMD, and no further EMD has developed to date. In the present case, the bone marrow was in morphologic and molecular remission during the course of recurrent EMD. The accumulation of detailed cases is needed to elucidate the pathogenesis, predisposing factors, and optimal therapy for EMD in APL after SCT.

Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Combined Modality Therapy; Female; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Neoplasm Proteins; Oncogene Proteins, Fusion; Oxides; Radiography; Recurrence; Remission Induction; Sarcoma, Myeloid; Stem Cell Transplantation; Translocation, Genetic; Transplantation, Homologous; Tretinoin

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic leukemia with specific clinical, morphologic and genetic features and a good response to all trans retinoic acid (ATRA). However, extramedullary (EM) relapse is an interesting feature of these cases, especially those treated with ATRA. Recently, we have encountered an EM relapse in the pleura in a case with APL receiving an ATRA containing regimen. This case is reported and the relevant literature is reviewed.

Topics: Adult; Humans; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Male; Pleural Effusion, Malignant; Pleural Neoplasms; Recurrence; Sarcoma, Myeloid; Tretinoin

Topics: Antineoplastic Combined Chemotherapy Protocols; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Epidural Space; Humans; Male; Middle Aged; Sarcoma, Myeloid; Spinal Neoplasms; Translocation, Genetic; Tretinoin

Topics: Adult; Antineoplastic Agents; Bone Marrow; Ear Neoplasms; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Promyelocytic, Acute; Recurrence; Sarcoma, Myeloid; Transplantation, Homologous; Tretinoin