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WOS: 000411827200025, PubMed ID: 28961828, Background: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. Patients and methods: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. Results: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. Conclusions: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Disseminated infections caused by members of the Fusarium fujikuroi species complex (FFSC) occur regularly in immunocompromised patients. Here, we present the first human case caused by FFSC-member Fusarium andiyazi. Fever, respiratory symptoms and abnormal computerised tomography findings developed in a 65-year-old man with acute myelogenous leukaemia who was under posaconazole prophylaxis during his remission-induction chemotherapy. During the course of infection, two consecutive blood galactomannan values were found to be positive, and two blood cultures yielded strains resembling Fusarium species, according to morphological appearance. The aetiological agent proved to be F. andiyazi based on multilocus sequence typing. The sequencing of the internal transcribed spacer region did not resolve the closely related members of the FFSC, but additional data on partial sequence of transcription elongation factor 1 alpha subunit did. A detailed morphological study confirmed the identification of F. andiyazi, which had previously only been reported as a plant pathogen affecting various food crops.

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI) is a lipophilic agent that has been proposed as a useful tracer for the detection of disease sites in patients with multiple myeloma (MM). We performed a prospective study to determine the potential of 99mTc-MIBI imaging for the evaluation of the extent of primary disease in patients with advanced stage MM, compared with skeletal survey and bone scintigraphy. Twenty patients with advanced stage MM at initial diagnosis underwent whole-body 99mTc-MIBI imaging, together with contemporaneous skeletal survey and bone scintigraphy. The findings of 99mTc-MIBI imaging were correlated with the results of skeletal survey and bone scan. All 99mTc-MIBI scans were positive for the presence of active MM, whereas skeletal surveys were positive in 18 patients (90%) with osteolytic lesions. Bone scintigraphy demonstrated MM in only 15 patients (75%). In two patients with no detectable lesions on skeletal survey, 99mTc-MIBI imaging revealed uptake in the spine, corresponding to the abnormalities seen on magnetic resonance imaging (MRI). With respect to the localization of bone lesions, 99mTc-MIBI imaging was superior to bone scintigraphy in 15 patients (75%) and had concordant results with bone scintigraphy in four (20%). 99mTc-MIBI imaging is a very sensitive imaging modality for the identification of the extent of disease in patients with advanced MM. It is clearly superior to bone scintigraphy and complements the results of skeletal survey by finding additional disease sites. Hence, in active MM patients, 99mTc-MIBI imaging has the potential to detect bone marrow disease that cannot be detected by skeletal survey and bone scintigraphy.

We read with great interest the article by Ault et al1 in a recent issue of Journal of Clinical Oncology, describing the results of pregnancy among patients with chronic myeloid leukemia (CML) treated with imatinib. We would like to add some points and bring attention to some questions concerning imatinib and pregnancy. Tyrosine kinases (TKs) are one of the most critical groups of signaling molecules for the cellular regulation of proliferation, differentiation, survival, function, and motility, and various tumors overexpress TKs, leading to uncontrolled mitogenic signals to the neoplastic cells. Imatinib (Gleevec or Glivec; Novartis, Basel, Switzerland) is a small-molecule tyrosine kinase inhibitor active against BCR-ABL, c-ABL, ARG, PDGF-r, and c-KIT.2 Although imatinib has been used primarily for cancers such as CML, use of imatinib has demonstrated that tyrosine kinase inhibitors can have a wide therapeutic window and heralds the era of targeted cancer and noncancer disease therapy. Information about the effects of drugs on the developing embryo is derived primarily from animal experiments and case reports describing the outcomes of pregnancies complicated with drug. Some drugs can be teratogenic in some animal species, but not in humans. In preclinical studies imatinib was found to be teratogenic in rats, but not in rabbits, and impaired spermatogenesis was observed in rats, dogs, and monkeys; however, there was no evidence that imatinib was genotoxic. These observations lead to concerns that men treated with imatinib may have reduced sperm counts. Clinical experience has not shown this to be true because male patients who were receiving treatment of imatinib were partners in 18 pregnancies and four healthy infants. Owing to teratogenicity data in rats (causing exencephaly or encephalocele, and absent or reduced frontal and absent parietal bones), it is recommended that women treated with imatinib be aware of the potential teratogenicity of imatinib, and effective contraception should be used during imatinib therapy to prevent pregnancy.2 Hensley and Ford2 reported 26 pregnancies (15 in clinical trials, 11 in nonclinical trials) among women taking imatinib. Most of the patients opted for elective therapeutic abortions, and only three patients carried their pregnancies to term. Two infants were healthy, and one infant had hypospadias. Recently, eight patients with CML who became pregnant while receiving imatinib therapy were reported from different areas of the world.3-7 All of the fetuses had been exposed to imatinib during the first trimester, and four fetuses have also been exposed to imatinib during the second and third trimesters. Six of the reported eight pregnancies proceeded to term with healthy infants, and two were terminated with unsatisfactory outcomes—one had spontaneous abortion4 and the other had a dead fetus with meningocele.7 More recently, Ault et al1 reported their experience on 19 pregnancies involving 18 patients (10 female and eight male patients) who conceived while receiving imatinib for the treatment of CML. Three pregnancies (involving two female patients and one male patient) ended in spontaneous abortion, and one patient had an elective abortion. All other pregnancies were uneventful. Two of 16 infants had minor abnormalities at or shortly after birth (hypospadias in one and rotation of small intestine in another) that were surgically repaired.

Background Although bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event. Methods To underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow. Results The main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO). Conclusion Our series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors.