Search

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.

Although it is well known that numerical and structural chromosomal aberrations are common in leukemic cells, tetraploidy and near-tetraploidy is a rare entity in acute myeloid leukemia (AML) [1-4]. We describe a rare case of AML-M0 with near-tetraploidy and superior vena cava syndrome (SVCS) due to a large mediastinal granulocytic sarcoma (GS). A 25-year-old male was admitted to our hospital with a progressive non-productive cough, dyspnea, pain on the left upper extremity and weight loss. One month ago, he was treated with a diagnosis of venous thrombosis because of the pain and swelling on his left upper extremity. At the time of admittance, physical examination revealed dyspnea, facial edema, swelling of the neck and upper extremities and dilated jugular and superficial veins of the chest. Peripheral lymph node or organomegaly was absent. His hematological findings were: hemoglobin, 14.1 g dl−1; hematocrit, 41.6%; MCV, 87.5 fl; WBC, 15.3 × 109 l−1 with 15% polymorphonuclear cells; 22% bands; 37% lymphocytes; 26% resembling blastic cells; and platelets 284 × 109 l−1. The chest X-ray showed enlarged mediastinum and thorax computed tomography (CT) demonstrated a multi-lobar mass with a diameter of 9 × 5 cm in the anterior mediastinum which also compressed the superior vena cava (Figure 1A). Abdominopelvic CT scan was normal. Mediastinoscopy was performed for definite diagnosis. The biopsy specimens from mediastinal mass revealed diffuse malignant infiltration in lipomatous tissue, which consisted of round, large sized cells. Nuclei were large, vesicular and contained two or three nucleolus. Cytoplasm was moderate in amount and clear. The specimens showed negativity for all of the antibodies and staining except for myeloperoxidase (MPO), CD34 and TdT (Figure 1B). Bone marrow aspirate revealed the presence of large blasts with a relatively low nuclear-cytoplasmic ratio, moderate chromatin pattern, two-to-three prominent nucleoli, no cytoplasmic granules and few cytoplasmic vacuolization. Most of the cells had heterogeneous shaped nuclei. No Auer rod was seen (Figure 1C). Cytochemistry revealed negativity for MPO, Sudan black B, periodic acid Schiff, combined esterase and acid phosphatase. Flow cytometric studies of the bone marrow cells revealed positivity for CD13, CD33, CD34, CD45, CD7 and HLA-DR. Cytogenetic analysis showed near tetraploidy (Figure 1D). Results of cytogenetic analysis of 20 metaphases of the bone marrow cells were as follows; 102, XXYY, +13, +14, +14, +15, +16, +18, +19, +21, +21, +22 [6] / 104, XXYY, +X, +Y, +3, +4, −7, −8, +10, +11, +13, +13, −14, +15, +15, +19, +21, +21, +22, +22 [9] / 98, XXYY, +3, +4, −6, +8, −11, +13, +14, −16, +19, +20, +21, +21 [5]. Neither apparent structural rearrangement nor normal clone was identified. Upon establishing the diagnosis (AML-M0/near tetraploidy+/mediastinal GS+) [5], he was given an induction chemotherapy consisting of daunorubicin (45 mg m−2 per day, days 1–3) and cytarabine (100 mg m−2 per day continuous infusion, days 1–7) and bone marrow remission was achieved. Then, he received the first consolidation chemotherapy consisting of idarubicin (10 mg m−2 per day, days 1–3) and cytarabine (1000 mg m−2 per day, days 1–6), followed by second consolidation chemotherapy consisting of cytarabine (6 gr m−2 per day, days 1–3) and 1800 cGy radiotherapy on mediastinum. The symptoms of SVCS improved gradually after the 5th day of induction chemotherapy. Likewise, the mediastinal mass decreased in size by 30% after induction chemotherapy, 70% after consolidation chemotherapies and disappeared completely after the completion of radiotherapy (Figures 1E and F). Presently, he is in the 10th month of his complete remission without any recurrence in the disease or GS.

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.

PubMedID: 25231929 Current treatment modalities can cure up to 70–80 % of patients with classical Hodgkin lymphoma. Approximately, 20–30 % of patients require further treatment options. Brentuximab vedotin has been approved for the treatment of relapsed and refractory Hodgkin lymphoma. In the present study, we report the experience with brentuximab vedotin as single agent in 58 patients with relapsed or refractory Hodgkin lymphoma. The objective response rate was 63.5 % with 13 complete responders (26.5 %) among 49 patients evaluated at the early phase of treatment (2–5 cycles). Upon treatment prolongation (?6 cycles), 37 patients achieved a final objective response rate of 32.4 % with 21.6 % of complete and 10.8 % of partial response. Overall survival at 12 months was 70.6 %, and progression-free survival at 12 months was 32.8 %. Median overall survival could not be reached and median progression-free survival was 7 months. While the median duration of response was 9 months in the whole cohort, it was 11.5 months in the complete responders. Complete response rates in patients treated with >3 chemotherapy regimens before brentuximab vedotin were significantly lower (p = 0.016). Fourteen patients were subsequently transplanted. In conclusion, brentuximab vedotin provided a bridge to transplantation in approximately one quarter of the patients. The declining response rates during the course of treatment suggest that transplantation should be implemented early during brentuximab vedotin treatment. © 2014, The Author(s).

An activating mutation of Janus kinase 2 (JAK2-V617F) was previously described in chronic myeloproliferative disorders (MPD). In previously published studies, the frequency of the JAK2-V617F mutation was determined to be 80–90 % for patients with polycythemia vera (PV) and 40–70 % for essential thrombocythemia (ET). In this study, we analyzed the relationship between the JAK2-V617F mutation and clinical-hematological parameters in Turkish patients with MPD and compared these findings with published studies from other geographic regions. A total of 148 patients were studied; of which, 70 were diagnosed with PV and 78 with ET. The mutation status of JAK2 was determined using a tetra-primer polymerase chain reaction. We found that 80 % of the PV group and 42 % of the ET group were positive for the JAK2-V617F mutation. When all patients were analyzed, the levels of white blood cells, hemoglobin and splenomegaly were significantly different in patients with the JAK2-V617F mutation (p

Imatinib has shown significant clinical and cytogenetic success in the treatment of chronic myeloid leukemia. Although resistance has been observed in a proportion of patients, sudden blastic crisis is a rare event during imatinib therapy. We describe a 24-year-old male patient with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who developed sudden blastic crisis in the 24th month of imatinib therapy, with loss of complete cytogenetic response. At this time, the patient had splenomegaly, severe anemia, thrombocytopenia, and leukocytosis. Bone marrow aspirate revealed the presence of massive blastic infiltration with myeloid morphology. Flow cytometric analysis of the bone marrow cells showed positivity for CD45, CD34, CD13, CD33, CD19, CD41, C1361, and glycophorin-A. Trephine biopsy specimens showed 100% cellular marrow with diffuse infiltrate by blasts. A reticulin stain of the bone marrow biopsy section demonstrated severe diffuse fibrosis. Cytogenetic analysis by fluorescence in situ hybridization (FISH) revealed that 92% of the cells were positive for the BCR/ABL fusion signal and had increased copy numbers for chromosomes 8,13,19, and 21. The patient's prognosis was unfavorable. In conclusion, chronic myeloid leukemia remains complex and includes unanswered questions. The presented case with a rare event during imatinib therapy highlights the need for the continued monitoring of residual disease and the development of strategies to eliminate residual leukemia cells in patients showing a complete cytogenetic response. Novartis İlaç

Objective: The aim of this study was to determine the factors associated with the prognosis of newborns born to mothers with idiopathic thrombocytopenic purpura (ITP), and to compare the infants with/without thrombocytopenia in terms of maternal and neonatal characteristics. Study Design: We reviewed the charts of 29 parturients with ITP and their newborns who were born between January 1998 and December 2008. Result: A total of 16 (55%) gravidas had been diagnosed with ITP before pregnancy and 13 (45%) were diagnosed during pregnancy. Thrombocytopenia was observed in 21 gravidas. In total, 17 (58%) gravidas received treatment to increase the platelet count. The majority of deliveries (72.5%) were vaginal. The infant platelet counts at birth ranged from 20 to 336 x 10(9) per liter. None of the neonates had complications attributable to the mode of delivery. Normal platelet counts were determined in 15 newborns, whereas 14 infants had thrombocytopenia at birth. Three (10.3%) neonates had mild, four neonates (13.7%) had moderate and seven neonates (24.1%) had severe thrombocytopenia. The age of the mothers having infants with thrombocytopenia was significantly higher (30 +/- 5.3 vs 25.3 +/- 3.8 years), most of the infants (10/14 (71%)) were males (P

Thrombotic thrombocytopenic purpura (TTP) is a classic, but not a common disorder of hematology. Plasma exchange (PE) was shown to nearly reverse its 90% mortality rate. However, there are still some fatal outcomes in this dramatic disease. We present our experience of plasma exchange plus corticosteroids for the treatment of TTP in our hospital. Patients with TTP diagnosed between January 1996 and January 2005 were identified by a retrospective review of records of the Uludag University Hospital, Bursa (the largest referral center for adults with this disorder in this region with an estimated 2.2 million residents), which performs all therapeutic PE in the southern Marmara region in Turkey. A total of 11 (6 male, 5 female) patients were treated for TTP during this period. The median age was 39 years (range 18-49). One plasma volume exchange daily plus steroid was the principle treatment in all patients. A total of 295 PE sessions were performed. We have obtained six complete responses (CR) and three partial responses (PR) with daily PE and steroid (response rate 9/11). One of our primary refractory patients was saved with pulse steroid + cyclosporine + vincristine. Now, he is disease free for over one year. The other refractory patient did not develop any response to salvage therapy and expired on day 15 with status epilepticus and ventilator related pneumonia (mortality rate 1/11). A CR was obtained with adjuvant treatments in all three PR patients. Only one CR patient developed an early relapse (early relapse rate in CR patients 1/6). She was treated successfully with daily PE plus vincristine. Our median follow up period was 25 months (range 9-108). Considering our local population, our annual incidence is only about 0.63 new cases per one million people. This figure is considerably less than the data from US, which indicated an incidence of 3.7 cases per 1,000,000. To our knowledge, there is no high variability in the incidence of TTP in the different geographical regions of the world. It suggests that considerable number of patients escaped notice. We hope that, demonstrating the successful outcome, this article serves to urge primary physicians to keep in mind the diagnosis of TTP and refer suspected cases quickly.

Mediterranean spotted fever (MSF), Boutonneuse fever, is a tick-borne disease caused by Rickettsia conorii and is endemic in the Mediterranean region. Although MSF is usually a benign infectious disease, unusual manifestations that have been mainly reported in severe forms, typically among elderly patients or those with underlying diseases, complicate the diagnosis. A 39-year-old woman, a resident of Bursa, Turkey, was admitted with a 5-day history of fever, headache, and malaise and a 3-day history of rash. Physical examination showed fever and maculopapular rash involving the trunk, extremities, palms, and soles. Hematological findings were as follows: Hb 10.8 g/dL, WBC 1.7  109/L with 62% polymorphonuclear cells; 9% bands; 20% lymphocytes; 6% metamyelocytes; 3% myelocytes;and platelet count 46.8  109/L. Laboratory studies revealed an elevated CRP (13 mg/L), accelerated ESR (60 mm/h), hypoalbuminemia (2.5 mg/L),and slightly elevated serum aspartate aminotransferase (53 UI/L) and lactate dehydrogenase (386 UI/L). Bone marrow smear showed hypercellular marrow with activation of myeloid cells. After 3 days of hospitalization, we learned that she has a dog in her yard. A ‘‘tache noire,’’ the typicaleschar at the site of the tick bite, was observed on the right inguinal region with more elaborate physical examination. Treatment with doxycycline (200mg/day) was started. Resolution of fever and normalization of haematological findings were observed on the 4th and the 6th days of treatment, respectively.

Bone marrow necrosis (BMN) is a rare disorder defined pathologically as necrosis of myeloid tissue and medullary stroma in large areas of the bone marrow with preservation of bone [1]. Although postmortem reports show a higher prevalence of this disorder, the prevalence of BMN is highly variable and a relatively rare entity diagnosed during life [2]. A 19-year-old boy was hospitalized in June 2004 with a 1-week history of fever, anorexia, dysphagia, and cough. He was diagnosed as having HL 3 years ago. Because optimal response was not achieved with chemotherapies, autologous bone marrow transplantation was performed in September 2003. Physical examination at the time of presentation revealed fever 38.78C, pale appearance, extensive cutanaous ecchymoses, left inguinal lymphadenopathy, and hepatomegaly. Laboratory findings were as follows: hemoglobin 4.6 g/dl; white blood cell count 0.13 109 /L; platelet count 9 109 /L; lactate dehydrogenase (LDH) 144 UI/L (125–250), and alkaline phosphatase (ALP) 74 UI/L (35–150). ESR was 110 mm/h. Thorax and abdominal CT scans revealed progression of disease. The patient had febrile neutropenia and was put on antibiotherapy. All cultures for bacteria and fungi were negative as well as serologic tests for viruses including those that can cause cytopenia. Bone marrow aspiration resulted in ‘‘dry tap’’ and a biopsy specimen from the posterior iliac crest showed the necrosis of bone marrow and trabeculae. In the biopsy specimen, the marrow space was totally replaced by coagulative necrotic cells with preservation of only the basic outlines. Bone marrow scintigraphy showed low uptakes within the bone marrow, especially in the iliac bone, with increased uptakes in the axial bone and hand and foot phalanx. Two weeks later, the patient succumbed with massive pulmonary hemorrhage albeit supportive care.

Between April 2000 and May 2005, 350 bacteraemic episodes occurred among patients treated in our haematology unit. Two hundred and twenty-eight of these episodes were caused by Gram-positive pathogens, most commonly coagulase-negative staphylococci and Staphylococcus aureus. One hundred and twenty-two episodes were due to Gram-negative pathogens, with a predominance of Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa. Bacillus bacteraemias constituted 12 of these episodes occurring in 12 patients, and accounted for 3.4% of all bacteraemic episodes. Of the 12 strains evaluated, seven were Bacillus licheniformis, three were Bacillus cereus and two were Bacillus pumilus. Seven episodes presented with bloodstream infection, three with pneumonia, one with severe abdominal pain and deterioration of liver function, and one with a catheter-related bloodstream infection. B. licheniformis was isolated from five patients who had been hospitalized at the same time. This outbreak was related to non-sterile cotton wool used during skin disinfection. B. cereus and B. licheniformis isolates were susceptible to cefepime, carbapenems, aminoglycosides and vancomycin, but B. pumilus isolates were resistant to all antibiotics except for quinolones and vancomycin. Two deaths were observed. In conclusion, Bacillus spp. may cause serious infections, diagnostic and therapeutic dilemmas, and high morbidity and mortality in patients with haematological malignancies. Both B. cereus and B. licheniformis may be among the 'new' Gram-positive pathogens to cause serious infection in patients with neutropenia.

Introduction Reversible posterior leukoencephalopathy syndrome (RPLS) is a recently described clinical and radiological entity comprising headache, seizures, altered level of consciousness and visual disturbances in association with transient posterior cerebral white-matter abnormalities. Method We report a young woman with Burkitt's lymphoma who developed RPLS after combined chemotherapy administered during the tumor lysis syndrome. Results The symptoms in this patient fitted well with those of RPLS; they included abrupt alterations in mental status, seizures, headache, visual changes and characteristic neuroradiological findings. She was given further combination chemotherapy without any neurological complications, at which time she had already recovered from both RPLS and tumor lysis syndrome. Conclusion Although many etiological factors have been reported in the development of RPLS, the underlying mechanism is not yet well understood. With prompt and appropriate management, RPLS is usually reversible, and chemotherapy can be continued after complete recovery from RPLS. We suggest that tumor lysis syndrome should be considered as a contributory factor to the development of RPLS in patients for whom treatment with combined chemotherapy for hematological malignancies is planned.

We read with great interest the article by Disel and colleagues [1] in a recent issue of Leukemia Research that described a case of acute myelogeneous leukemia (AML) with bilateral ear neutrophil poor Sweet's syndrome (SS). We would like to describe and share our experience in a patient with AML who developed bilateral eyelid SS and add some points concerning the SS. Sweet's syndrome, also referred to as febrile neutrophilic dermatosis, is characterized by fever, neutrophilic leukocytosis, painful red papules, nodules and plaques that respond readily to corticosteroid therapy [2], [3]. Although SS has been linked to hematologic malignancies, the frequency of SS with leukaemia is even lower in patients with neutropenia [4].

(2004). Primary Non-Hodgkin's T-cell Lymphoma of Bone. Leukemia & Lymphoma: Vol. 45, No. 8, pp. 1719-1720.

Although infrequently seen, the management of cancer during pregnancy can be difficult for patients, their families and physicians. The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 26-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in chronic phase by using only leukapheresis. She was treated with leukapheresis until her delivery at 36 weeks of gestation. The procedure was without significant adverse effects on the patient or fetus. We applied a total of 15 leukapheresis treatments throughout the pregnancy. The patient gave birth vaginally to a healthy 2800 g boy at 36 weeks of gestation. We conclude that leukapheresis may provide an alternative treatment to chemotherapy, alpha-interferon or imatinib in pregnant patients with CML, particularly with concern over their potential teratogenic and other adverse effects.

We describe the successful management of a 30-year-old woman in the second trimester of her pregnancy with chronic lymphocytic leukemia (CLL) in stage IV by using only leukapheresis. We applied three sessions (courses) of leukapheresis throughout the pregnancy. The procedure did not have any significant adverse effect on the patient and the fetus. The patient gave birth vaginally to a healthy boy, weighing 3100 g, at 39 weeks of gestation. Seven months after delivery, Richter's syndrome developed in the patient. We conclude that leukapheresis may provide an alternative for palliative treatment to chemotherapy in pregnant patients with CLL. To our knowledge, this is the fourth reported case of CLL in pregnancy, and the first management of CLL during pregnancy with leukapheresis.

We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by preeclampsia, one by ablatio placentae, and one by intrauterine death. Seven mothers received corticosteroid treatment, four high-dose immunoglobulin therapies, and one underwent splenectomy in the second trimester of gestation. At the time of delivery six mothers had normal platelet counts and seven had low platelet counts. Nine deliveries were by vaginal route and four were by cesarean section. Eleven infants were born with normal platelet counts and one was thrombocytopenic at the time of delivery. No infant showed any clinical signs of hemorrhage and there were no neonatal complications. Two fetuses died; one of them because of ablatio placentae and the other was intrauterine dead. In conclusion, ITP in pregnancy requires the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, anesthesiologist, and neonatologist is essential.

The incidence of acute leukemia in pregnancy is low and the management of acute leukemia during pregnancy is difficult. We have observed a total of 10 pregnancies in 8 patients. Six of the patients had acute myeloblastic leukemia (AML) and two of them had acute lymphoblastic leukemia (ALL). Three of the pregnancies were diagnosed when the leukemia was in remission, six at the time of leukemia diagnosis and one at the time of leukemic relapse. Six of the pregnancies were found in first trimester, three in the second and one early in the third. Three pregnancies ended with spontaneous abortion, three with intrauterine death and three with medical termination. One of spontaneous abortions and one intrauterine death developed during combination chemotherapy (daunorubicin, cytarabine). Only 1 healthy baby survived from the 10 pregnancies and this child was the not exposed to chemotherapeutic agents. None of the cases had gynecologic and obstetric complications. Five of eight pregnant women with leukemia died because of the primary disease.

Primary pulmonary lymphoma arising from mucosa- or bronchus-associated lymphoid tissue (MALT or BALT) is a rare disease.1,2 We report a 30 year old man with low grade B cell BALT lymphoma who presented with a bulky mass in the lung and was treated successfully with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) combined chemotherapy. The patient was admitted with a dry cough, shortness of breath, back pain, and progressive infiltrates on chest radiographs. He had no …

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.