Already weeks after allo HSCT she achieved

Already 4 weeks after allo-HSCT she achieved an almost normal differential WBC count with monocytes around 1×109, total lymphocytes of 0.6×109. A new lymphocyte profile showed an almost normal amount of NK-cells (0.15×109) and CD4 T-cells (0.18×109). She showed a full donor blood chimerism in October 2013.
Discussion In this case report we describe a young woman that presented with a long history of condylomata and microcytic anemia due to a combination of MDS associated with the DCML syndrome and iron deficiency demonstrating that an overlap of clinical symptoms may complicate diagnosis in patients with GATA2 mutations. Genetic lesions in GATA2 that lead to Emberger syndrome seem to be affecting endothelial g-quadruplex of the lymphatic system, but vascular problems have not been described in patients with GATA2 mutations, to our knowledge. Our patient suffered from a non-ST-elevation myocardial infarction (NSTEMI) caused by a stenosis in the LAD in the absence of cardiac risk factors or a family history of heart disease and is, thus, most likely triggered by anemia due to a massive menstrual bleeding aggravated by a uterine myoma. Some clinical findings may be associated with distinct type of mutation causing GATA2 haploinsufficiency. However, in two large patient cohorts published recently, diversity of phenotype in patients with GATA2 mutations was shown for the first time [4,11]. 84% of the patients in this study met the diagnostic criteria for MDS whereas bone marrow findings in patients with GATA2 mutations seem to differ from those with typical MDS [4]. Instead, patients with GATA2 mutations present with a hypocellular bone marrow, increased reticulin fibrosis and atypical megakaryocytes in almost all cases. In addition cytogenetic abnormalities such as monosomy 7 or trisomy 8 are frequent [12,13]. In the case presented here, repeated bone marrow biopsies showed rather discrete changes and considering the absence of cytogenetic aberrations, it was challenging to diagnose MDS. Nevertheless, exome sequencing revealed the presence of a somatic ASXL1 mutation. Myeloid transformation induced by acquired lesions of ASXL1 in patients with constitutional GATA2 mutations were previously reported [12–14]. This demonstrates that an early diagnosis and evaluation for allo-HSCT is crucial for patients with GATA2 mutations and genetic counseling should be offered to affected families.
Introduction Bone marrow fibrosis is known to occur in several neoplastic and non-neoplastic conditions. Among neoplastic conditions such as acute leukemia, it is most often seen with acute megakaryoblastic leukemia [1]. Acute promyelocytic leukemia (APL) presenting with marrow fibrosis is a rare entity, with few cases reported in the past [2–4]. In one case series a reversible bone marrow collagenous fibrosis has been reported in cases of APL treated with tretinoin [5]. However literature search did not reveal any such occurrence of bone marrow fibrosis following therapy with arsenic trioxide (ATO) in a case of APL. Here we report a case of 44 year old female who was diagnosed as APL with t(11;17), who subsequently developed bone marrow collagenous fibrosis following induction therapy with ATO.
Case history A 44 year old female, known hypothyroid and hypertensive on regular medication, presented with spontaneous skin bleed for five months, generalized weakness, fatigability and menorrhagia for three months duration. She was diagnosed to have fibroid uterus and underwent diagnostic dilatation and curettage (D&C) for her complaints at an outside hospital. As her bleeding per vaginum did not stop after D&C, hysterectomy was performed. During the post operative period she was found to have high total leukocyte count (TLC). Subsequently the patient developed pain abdomen, found to have hemoperitoneum and exploratory laparotomy was carried out to achieve hemostasis. Since she had high TLC, bone marrow examination and cytogenetics were carried out which revealed abnormal promyelocytes and 45X, −X, t(11;17)(q23;q21) respectively (Fig. 1). Based on the morphological and cytogenetic abnormality, diagnosis of APL was made and the patient was transferred to our center for further management. On examination she had pallor, fever, multiple purpuric spots over upper and lower limbs, a midline abdominal suture wound with gaping and necrotic slough along with foul smelling discharge. Respiratory system examination revealed diminished breath sounds in left infrascapular region suggestive of pleural effusion. CT scan chest showed bilateral ground glass opacities suggestive of fungal pneumonia and left sided pleural effusion. There was no organomegaly or peripheral lymphadenopathy. Laboratory parameters revealed hemoglobin of 69g/L, TLC of 35.39×109/L with a differential leukocyte count of 50% promyelocytes, 19% myelocytes, 01% metamyelocyte, 27% mature neutrophils, 03% lymphocytes and platelet count of 44×109/L. After admission to our center, her coagulation parameters remained within normal limits and there was no laboratory evidence of disseminated intravascular coagulation. Bone marrow examination revealed 45% hypergranular promyelocytes with 03% blasts, 40% maturing myeloid forms and neutrophils, 06% erythroid cells and 06% lymphocytes. There were no Auer rods or fagot cells seen. Myeloperoxidase stain showed strong MPO positivity in these promyelocytes. The bone marrow biopsy showed near total replacement by immature myeloid forms without marrow fibrosis (Fig. 1). In view of foci of infections involving lung and gaping infected wound in anterior abdominal wall, patient was not offered Inj daunorubicin and all trans retinoic acid. Instead she was started on ATO at a dose of 0.15mg/kg body weight along with supportive antibiotics and antifungals. During therapy she became afebrile, her abdominal wound healed and lung lesions resolved. The TLC reduced gradually along with signs of maturation in the peripheral smear. However by day+45, patient developed pancytopenia and hence bone marrow examination was performed to assess the disease status. Bone marrow aspiration yielded a dry tap and the bone marrow biopsy tissue obtained was pale and gray white on gross examination. The peripheral smear received along with the bone marrow revealed an occasional promyelocyte and the bone marrow aspirate smears were paucicellular which revealed 03% blasts, 08% promyelocytes, 11% myelocytes, 07% metamyelocytes, 10% neutrophils and 61% lymphocytes. The bone marrow biopsy tissue revealed dense diffuse marrow fibrosis with extensive collagen deposition suggestive of grade III marrow fibrosis [6] confirmed on Masson trichrome stain, with entrapped immature myeloid forms of similar morphology observed in the diagnostic marrow (Fig. 2). The therapy with ATO was discontinued in view of bone marrow fibrosis and patient was observed with supportive care. Subsequently, on follow up the TLC and promyelocyte count in peripheral smear increased in number. As the patient did not have any foci of infection, she is now started on induction chemotherapy with daunorubicin and all-trans retinoic acid.