Niraparib-induced pure red cell aplasia.

INTRODUCTION: Niraparib, a strong poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, contributed significantly to progression-free survival as a maintenance therapy in the platinum-sensitive period in both first-line and recurrent ovarian cancer, regardless of the BRCA mutation. Grade 3-4 anemia, which has a manageable side effect profile, especially hematological, is seen in almost 1 out of every 4 patients. To the best of our knowledge, there has been no reported case of pure red cell aplasia (PRCA) induced by niraparib treatment. CASE REPORT: A 65-year-old woman diagnosed with stage 3 serous carcinoma of the tuba received niraparib front-line maintenance treatment had grade 4 anemia after 3 months of niraparib treatment. She underwent bone marrow aspiration and biopsy because of refractory anemia, which needs red blood cell (RBC) transfusions despite interruption of treatment. MANAGEMENT AND OUTCOME: The patient was treated with 1 mg/kg methyl prednisolone, after histopathological assessment was consistent with PRCA. The hemoglobin count returned to the normal range with steroid treatment. DISCUSSION: In daily practice, it should be kept in mind that in the case of refractory anemia induced by niraparib, the underlying cause might be PRCA and can be improved with steroid administration.

Refractory anaemia in an immunocompromised patient--what is it?

Anaemia is common among human immunodeficiency virus (HIV)-infected patients. It may be directly attributable to the virus or may be caused by opportunistic infections, neoplasms or drugs that cause either bone marrow suppression or haemolysis. Pure red cell aplasia (PRCA) is an uncommon haematological disorder that causes severe transfusion dependant anaemia. We report a 36 year-old female with HIV infection who developed anaemia which did not improve even after discontinuing the offending drug, namely Zidovudine. Routine investigations were unhelpful but her bone marrow study was consistent with pure red cell aplasia. She showed dramatic improvement with steroids with subsequent transfusion independence.

Deletion of the long arm of chromosome 5 (5q-) as a secondary event in the course of refractory anemia.

A 54-year-old chemical plant worker developed mild pancytopenia, with normal bone marrow morphology. Normal bone marrow cytogenetics were documented. The patient developed worsening anemia 5 years into his course. The bone marrow morphology remained normal, but four of 30 bone marrow metaphases examined showed deletion of the long arm of chromosome #5. Eight years into his course, the patient developed severe thrombocytopenia, and his bone marrow became hypercellular, with dysplastic changes. Deletion of the long arm of chromosome #5 was seen in all of 21 bone marrow metaphases examined. There had been no new exposure to potential mutagens during the course of the patient's illness. The occasional documentation of the late appearance of cytogenetic abnormalities during the course of clonal hematopoietic disorders implies that, in some cases at least, chromosomal abnormalities may not be primary pathogenetic events. The full expression of clonal disorders may require several pathogenetic events, which may occur in variable order.

Cytogenetics and occupational exposure to solvents: a pilot study on leukemias and myelodysplastic disorders.

In a pilot study, 57 patients affected by leukemias or myelodysplastic syndromes were interviewed to identify potential exposure to organic solvents. Cytogenetic analyses were performed in 40 of the 57 patients. Unlike previous investigations, no association was found between the occurrence of chromosomal abnormalities and exposure to organic solvents. An original finding was a strong association between solvent exposure and myelodysplastic disorders (4 certainly exposed and 1 possibly exposed out of 11 patients). Such an observation warrants confirmation from case-control studies.

Spontaneous remission in a patient with therapy-related myelodysplastic syndrome (t-MDS) with monosomy 7.

We describe a case of spontaneously reversible refractory anaemia, a subtype of myelodysplastic syndrome (MDS), with monosomy 7 secondary to chronic treatment with azathioprine (AZA) in a young renal transplant recipient. AZA was stopped after that conventional cytogenetics and fluorescence in situ hybridization (FISH) had demonstrated the existence of a monosomy 7 clone, 4 months later, haematological values had considerably improved and the karyotypic examination as well as the FISH analysis were normal. The spontaneous remission of this MDS with monosomy 7, which is usually associated with a particularly poor prognosis, could be due to the recovery of a better immunosurveillance following the withdrawal of AZA.

Deliberate overdose of uranium: toxicity and treatment.

A case is described of deliberate ingestion of 15 g of uranium acetate which resulted in acute renal failure requiring dialytic therapy for 2 weeks, refractory anaemia, rhabdomyolysis, myocarditis, liver dysfunction with a disproportionate coagulopathy and paralytic ileus. Despite significant elevations in plasma uranium levels, treatment with both calcium EDTA and calcium DTPA were ineffective in promoting uranium excretion. Six months later the initial significant renal impairment exists with a persistent incomplete Fanconi syndrome. Future options for management of this unusual cause of acute renal failure are discussed.

Persistent bone marrow failure with dysplastic features following pentostatin therapy for hairy cell leukaemia.

Myelodysplastic syndromes (MDS) have rarely been reported after treatment with nucleoside analogues, and mainly in patients who have also received alkylating agents. We report a patient who developed MDS (refractory anaemia with ring sideroblasts) after treatment with pentostatin (deoxycoformycin) alone.

Myelopathies during the course of multiple myeloma.

BACKGROUND: The development of acute non-lymphoblastic leukaemia (ANLL) or myelodysplastic syndromes (MDS) secondary to treatment of multiple myeloma (MM) is well known. In some cases the simultaneous appearance of MM and ANLL has been described. METHODS: In this series the simultaneous appearance of MM and various myelopathies in 91 untreated patients with MM, and the development of myelopathies during the course of the disease in 72 treated patients were studied. RESULTS: Simultaneous appearance of MM (IgA/lambda) and refractory anaemia with ring sideroblasts (RAS) was observed in one case (1.1%). Development of myelopathies in treated patients with MM was found in 4 out of 72 cases (cumulative risk at 8 years 28.3%). In one case (IgG/lambda MM) a myeloproliferative disorder (MPD) developed 6 years after the initial diagnosis. Cytogenetic analysis was normal. In the second patient (IgG/k MM) a similar MPD was observed 5 years after the initial diagnosis. The karyotype was 46, XX, -5 + t (20;?). The third patient with lambda light chain disease developed RAS 11 months after the initial diagnosis. The karyotype was 46, XY/hypodiploidy + M. Finally, the fourth case (IgG/k MM) developed ANLL (M4) 28 months after the initial diagnosis and the karyotype was 45, XX, -7, t(1;3). CONCLUSIONS: The simultaneous appearance of MM and various myelopathies is unusual and probably represents a neoplastic transformation of a single progenitor in both lymphoid and myeloid malignancies. On the contrary, the development of myelopathies during the course of treated patients is a common phenomenon. The time of development and the cytogenetic findings strongly suggest that they are related to treatment with cytostatics.

Hair dye use and other risk factors for leukemia and pre-leukemia: a case-control study. Italian Leukemia Study Group.

A case-control study was carried out to examine the relation of three subtypes of leukemia cells and refractory anemia with excess of blasts to selected behavioral and environmental factors. Cases aged 15 years or older were recruited in three hospitals located in Rome, Bologna, and Pavia, respectively. Outpatients who were either normal or had nonneoplastic hematologic disorders and were seen in the same hospitals as the cases were enrolled as controls. Two hundred fifty-two patients with acute myeloid leukemia, 100 with acute lymphocytic leukemia, 111 with refractory anemia with excess of blasts, 156 with chronic myeloid leukemia, and 1,161 controls were included in the study. Refractory anemia with excess of blasts and chronic myeloid leukemia were included because they are regarded as forms of pre-leukemia. Odds ratio estimates were generally imprecise, but associations were suggested between specific case subtypes and exposure to dark hair dye, selected occupations (shoemaker, painter, electrician, child care), residence in houses built with tuff, and smoking. Although the exploratory nature of the study and its limited statistical power preclude firm conclusions, its results are consistent with those of previous studies, and are in general biologically plausible.