Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Trephining”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,189 records · Page 66Linked to original sources
PubMed1994

[Reaction of the epiphyseal groove to groove-crossing bore-wire osteosynthesis. Results of a histomorphologic small animal study].

In young rabbits of five to six weeks of age we revealed bony bridging as constant reaction of the epiphyseal cartilage on drilling with a 2 mm diameter trephine into the distal femur growth plate. Gross growth disturbances will be the consequence of such partial closures. For this present study we inserted one 2 mm Kirschner-wire across the epiphyseal plate of the distal femur. The drilling was directed distally. During longitudinal growth the epiphysis moves away from the wire, that remains 8 weeks after the operation completely within the metaphyseal cancellous bone. Four, 8, 12 and 16 weeks postoperatively one group of the rabbits were sacrificed. After radiological examination of the explanted femurs fixation and embedding in methylmetacrylate for morphological examination was performed. Our histological results reveal, that the crossing Kirschner-wire does not irritate the growth plate, even the physiological structure of the epiphyseal cartilage in the direct contact to the metal implant is not altered. The defect within the epiphyseal plate left after the relative retraction of the wire caused by growth activity fills with cancellous bone. Its trabecular structure is markedly thinner than the spongy bone within the metaphysis and shows longitudinal orientation. These trabeculae undergo segmental disruption by the growth pressure of the surrounding epiphyseal plate. In consequence there is no bone bridging and growth alterations by the Kirschner-wire crossing of the epiphyseal plate. This proves experimentally the clinical experienced therapeutic value of Kirschner-wires for internal fixation of dislocated joint injuries.

Animals↗
PubMed1998

Non-secretory solitary plasmacytoma of the spleen.

A case of primary nonsecretory plasmacytoma of the spleen is reported. On laparotomy and splenectomy a 920 g spleen was removed, measuring 16 x 14 x 6 cm. The cut surface of the entire spleen showed that the tumour occupied most of the splenic tissue. A bone marrow aspirate and trephine, skeletal survey showed no signs of myeloma. Biopsy of the liver and regional lymph nodes was normal. Immunocytochemistry of the splenic tumour showed positivity for pan-B and plasma cell markers. After splenectomy the patient was treated with chemotherapy according to protocol VBCMP (M2).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Megakaryocyte precursors (pro- and megakaryoblasts) in bone marrow tissue from patients with reactive thrombocytosis, polycythemia vera and primary (essential) thrombocythemia. An immunomorphometric study.

To determine the number of megakaryocyte precursors (pro- and megakaryoblasts), an immunomorphometric study was performed on paraffin-embedded trephine biopsies of the bone marrow using a monoclonal antibody against platelet glycoprotein IIIa. Eighteen control specimens from patients with no evidence of any hematological disorder and a normal platelet count were selected and assessed together with the same number of specimens from patients with reactive thrombocytosis, polycythemia vera rubra (P. vera) or primary (essential) thrombocythemia (PTH). A strikingly proportionate increase in early megakaryocytes occurred in all patients enrolled in this study, compared with the controls. Moreover, there were no significant correlations between counts for precursors or total megakaryocytes per square millimeter of bone marrow with the corresponding values for platelets. This indicates that despite an orderly increase in immature forms in the bone marrow, the number of platelets circulating in the blood is influenced by other additional factors, such as the expanded platelet pool in the enlarged spleen. The non-disproportionate expansion of megakaryocyte precursors extends previous findings on progenitor cells of this lineage in vitro, particularly in PTH. Histological evaluation of the bone marrow of patients with P. vera and PTH indicated that megakaryopoiesis proceeded to the production of appropriate mature forms with no obvious excess of very small or blastic elements.

Antibodies, Monoclonal↗
PubMed1989

Bone marrow analysis of the myelodysplastic syndromes: histological and immunohistochemical features related to the evolution of overt leukemia.

Bone marrow trephines from 31 patients with an initial diagnosis of myelodysplastic syndromes (MDS) were examined and analyzed histologically and immunohistochemically. In those cases terminating in overt leukemia (6/31, 19%), the number of bone marrow mast cells was significantly reduced, compared with those which did not evolve to overt leukemia. The bone marrow lymphoid cells that may participate in immunosurveillance against the proliferation of blast cells were also significantly reduced in cases terminating in overt leukemia. However, S-100 protein-positive cells, which include histiocytes and suppressor T-cells, were increased in cases terminating in overt leukemia. The results indicated that examination of the bone marrow to determine the proportions of mast cells and lymphoid cells which may be involved in host defense systems may be useful in predicting the evolution to overt leukemia in MDS. In the present series, patients with a hypocellular marrow (5/31, 16%) did not progress to overt leukemia and had a significantly lower bone marrow reticulin content, a significantly lower megakaryocyte count, a relatively higher mast cell count and a significantly higher lymphoid cell count than those with a normocellular or hypercellular marrow. These findings may reflect the initial features of MDS or, possibly, that hypocellular MDS is an independent entity with a low potential for blastic proliferation.

Aged↗
PubMed1989

Alpha-smooth muscle actin is expressed in a subset of bone marrow stromal cells in normal and pathological conditions.

A series of 217 trephine bone marrow biopsies from adult patients and specimens from 16 fetuses and 5 infants were examined for the presence of stromal myoid cells (MCs) using a monoclonal antibody recognizing alpha-smooth muscle actin. In the normal adult bone marrow, stromal cells did not contain alpha-smooth muscle actin, whereas during fetal life, many alpha-smooth muscle actin-containing MCs were connected with vascular sinusoids in the primitive bone marrow. This cell type reappeared in various characteristic distribution patterns in adult bone marrow during different neoplastic and non-neoplastic conditions including metastatic carcinoma, Hodgkin's disease, multiple myeloma, hairy cell leukemia, acute myeloid leukemia (FAB M4, 5, 7) and chronic myelo-proliferative diseases. In general, the appearance of MCs was associated with a slight to pronounced increase in the deposition of reticulin and collagen fibers. We propose that bone marrow MCs represent a distinct subpopulation of fiber-associated or adventitial reticular cells undergoing cytoskeletal remodeling in response to various stimuli.

Actins↗
PubMed1990

Ultrastructure of neutrophilic granulopoiesis in the bone marrow of patients with chronic myeloid leukemia (CML). A morphometric study with special emphasis on azurophil (primary) and specific (secondary) granules.

In seven patients with chronic myeloid leukemia (CML) and ultrastructural and morphometric study was performed on neutrophilic granulopoiesis in bone marrow trephine biopsies. Bone marrow specimens from five patients without hematological abnormalities served as controls. In stable phases of CML, abnormalities of the maturing granulocytic lineage were most conspicuously expressed by an infrequently occurring nuclear disfiguration (blebs and disturbed bridging of segments). Morphometric evaluation included the numbers of azurphil (primary) and specific (secondary) granules, the cisternal length of the endoplasmic reticulum and the area of the mitochondrial profiles. These variables could be determined in early and late myeloblasts, promyelocytes, metamyelocytes, band cells and mature polymorphonuclear granulocytes. Statistical analysis with regard to control specimens demonstrated no significant differences in the total amount of neutrophil granules or of the other cell organelles.

Bone Marrow↗
PubMed1988

Prognostic features at diagnosis of chronic myeloid leukaemia with special emphasis on histological parameters.

A clinicopathological study was performed on 115 patients (56 males, 59 females; median age 48 yr) with chronic myeloid leukaemia (CML) to reveal initial clinical, but particularly histomorphological features of predictive value for survival. All patients had a trephine biopsy of the bone marrow and entered this study without prior selection. Overall survival was 36 +/- 27 months. In addition to multiple interactions between various disease features, multivariate regression analysis showed that of the clinical parameters age, liver size and level of LDH were primarily and most closely associated with prognosis. Of the histomorphological variables, megakaryocytes greater than 60 mm-2 bone marrow area and fibrosis displayed an unfavourable impact on survival on univariate calculation. On multivariate analysis, however, only pseudo-Gaucher cells remained significant, i.e. exerted an independent and favourable influence on prognosis. Histological features of predictive value were reviewed together with the different categories of a histopathological classification proposed for chronic myeloproliferative diseases by Georgii and co-workers.

Adolescent↗
PubMed2000

Detection of TNFalpha expression in the bone marrow and determination of TNFalpha production of peripheral blood mononuclear cells in myelodysplastic syndrome.

TNFalpha is a highly active cytokine which plays an important role in the regulation of apoptotic cell death, a mechanism involved in the pathophysiology of myelodysplastic syndrome (MDS). In this study we investigated the expression of TNFalpha of the bone marrow trephine biopsies by immunohistochemical method and the TNFalpha production of peripheral blood mononuclear cells by ELISA method in 15 patients affected by MDS. Five of seven patients without excess of blasts showed high or intermediate TNFalpha expression in the bone marrow biopsies, whereas two patients with excess of blasts were negative and one had low expression. The five CMML patients revealed low or intermediate expression. The production of TNFalpha by the PBMC was analysed in 10 patients, four patients with RA and two with CMML produced higher level of TNFalpha which increased after stimulation with phorbol myristic acetate, but none of the RAEB patients revealed increase in TNFalpha production. In conclusion we suppose that increased TNFalpha expression and production by PBMC may be an indirect evidence of the role of increased apoptosis in low risk MDS patients.

Adult↗
PubMed1997

Reconstruction of calvarial defects by bioresorbable ceramics: an experimental study in rats.

This study evaluated bioresorbable ceramics in the reconstruction of calvarial defects. Full-thickness defects were made in the calvaria of 40 adult Sprague-Dawley rats (350-450 g) with a standard 8-mm trephine drill. Three different materials were used for defect repair: (a) pure alpha-tricalcium phosphate (TCP), (b) surface-treated glass ceramic, (c) surface-treated glass ceramic plus 70/30 L/DL polylactic acid (volume ratio 45/55). The implants were pellets of 7.9 mm diameter and 2 mm thickness and were inserted press fit into the calvarial defects. Each of these materials was inserted into ten animals. Five animals were evaluated each after 6 weeks and 26 weeks. For each interval there was a control group of five animals. After 6 weeks the control defects exhibited negligible bone regeneration at the defect margins but showed substantially more bone regeneration after 26 weeks extending up to 2.5 mm into the defect space. The TCP specimens showed a number of multinuclear cells on the material surface and direct bone/implant contact in a few locations but no signs of gross degradation or volume reduction after 6 weeks. The amount of bone ingrowth and cellular behavior had not changed after 26 weeks with resorption still going on. Glass ceramic implants by contrast appeared to be even better tolerated after 6 weeks with remarkable bone ingrowth and broad osseous fixation of the pellet to the defect margins and beyond, while highly vascular connective tissue filled the remaining pores of the implant. After 26 weeks the material had been extensively degraded, leaving behind only a few remnants, which were surrounded by seams of highly vascularized and cell-rich resorptive connective tissue with newly formed bone tissue nearly bridging the defect. The polylactic acid/ceramic composite implants showed hardly any tissue ingrowth or degradation either after 6 or after 26 weeks. Hence all tested materials appeared to be well tolerated at the site of implantation. However, gradual replacement by bone ingrowth tended to occur only in implants without polylactic acid.

Animals↗
PubMed2006

[Arthroscopic meniscal suture].

OBJECTIVE: Restoration of the function of the meniscus by suturing a tear to prevent long-term degeneration. INDICATIONS: Unstable longitudinal meniscal tear in the red and red-white zones with an intact central fragment. Dislocated bucket-handle tear near the base in the presence of good-quality tissue. CONTRAINDICATIONS: Lesion of the central meniscal fragment. Meniscal tears in the white, avascular zone. Degenerative meniscal lesions. Complex meniscal lesions. Untreated knee ligament instability. Uncooperative patient. SURGICAL TECHNIQUE: Standard anterior arthroscopy approach. Revitalization of the tear margins and the perimeniscal synovial membrane, trephination of the base of the meniscus to promote healing. Fixation of the tear with a resorbable or nonresorbable suture size 2-0 to 0 USP by means of different suture techniques. "Outside-in technique": the suture is introduced from outside the joint through the base of the meniscus using a cannulated needle and is then pulled back out using a suture loop inserted with another cannulated needle. The U-suture is knotted over the joint capsule through a stab incision. "Inside-out technique": the suture is introduced using a needle through a guide cannula from outside the joint through the meniscus and joint capsule and then brought out of the joint. The U-suture is knotted over the capsule through a short skin incision. "All-inside technique": the suture loop is passed through the meniscal tear and knotted within the joint using a posterior arthroscopy approach. POSTOPERATIVE MANAGEMENT: Full weight bearing without a brace for short tears with one suture. For tears with two sutures, partial weight bearing for 4 weeks without a brace. For large tears with three to four sutures, partial weight bearing up to 20 kp for 6 weeks and restricted knee motion in a brace up to 0/0/60 degrees . RESULTS: The healing rate for knee joints with stable ligaments and an isolated meniscal tear is between 50% and 75%. In cases with simultaneous ACL (anterior cruciate ligament) plasty, the healing rate is > 75%; for unstable knee joints it is < 50%.

Adolescent↗
PubMed2001

Arrow wounds: major stimulus in the history of surgery.

To illustrate how the high incidence of arrow wounds provided a major stimulus for the development of surgery until a century ago, we conducted a literature search. Our research shows that archaic peoples developed considerable surgical skill for extraction of arrows, including thoracotomy and trephination. A classical Hindu veda describes a variety of extraction methods, and Homer's Iliad introduces the term iatros, which means "he who extracts arrows." Hippocrates of Kos and Galen, representatives of the humoral doctrine, both shunned surgical intervention and considered purulence a drainage of materia peccans (spoiled humors). Cornelius Celsus was the first to systematically differentiate removal of arrows per extractionem and per expulsionem. Celsus recommended the spoon of Diocles, an ancient surgical instrument specially designed for extraction of arrows. Paulus of Aegina favored rapid extraction, aggressive therapy, and ligature on both sides of a vessel before extraction efforts. Paulus was the first to describe a special instrument for the removal of detached arrowheads per expulsionem (propulsorium). In medieval Europe, the standard of surgery declined drastically. The classical procedure under the dominant influence of the humoral concept was to await pus before extraction and to burn the wound with boiling oil and a branding iron. Arab authors had conserved the knowledge of Celsus and Paulus, and in Europe a renewal was achieved by Ambroise Paré, who has been called the creator of modern surgery. The incidence of arrow wounds increased once more in the American West. Joseph H. Bill, a famous U.S. Army Surgeon preoccupied with arrow wounds, favored rapid extraction and aggressive therapy, and he taught recruits not to apply traction on the shaft. The principles established by Celsus, Paulus, Paré, and Bill not only mark important landmarks in the evolution of surgery but can also serve as the basis for modern treatment of arrow wounds, which still occur, although on a small scale.

General Surgery↗
PubMed2003

Review of the " Chirurgia" of Giovanni de Vigo: estimate of his position in the history of surgery.

Giovanni de Vigo, who was born in at Rapallo, Italy, lived in the early Renaissance period (1450-1525). In 1503, De Vigo became the personal surgeon to Pope Julius II. He wrote a surgical book, " Practica Copiosa in Arte Chirurgia," which was completed in 1514 and published in Latin. It was translated into English by Richard Traheron and printed by Edward Whytchurch in 1543. Vigo's " Chirurgia" consists of nine books ranging from a consideration of anatomy necessary for a surgeon, to sections on abscesses, wounds, ulcers, benign and malignant tumors, fractures and dislocations, pharmaceuticals, ointments and plasters, as well as sections on dentistry, exercise, diet, syphilis, among others. De Vigo introduces a novel approach for treating mandible dislocations and describes a trephine he invented, as well as a number of new instruments. Examination of his surgical piece demonstrates that he had a broad spectrum of knowledge in surgery based in part on the ancient Greek and Arabic medical literature but mainly on his personal experience. Giovanni de Vigo contributed significantly to the revival of medicine in the sixteenth century, and he can be considered as a bridge between Greek medicine of antiquity, Arabic medicine, and the Renaissance.

General Surgery↗
PubMed2002

CD34+ progenitor cells in idiopathic (primary) myelofibrosis: a comparative quantification between spleen and bone marrow tissue.

Previous studies on idiopathic (primary) myelofibrosis (IMF) are in keeping with the finding of an increased number of circulating CD34+ progenitor cells. However, dependent on the fibrosclerotic changes, little knowledge exists about quantitative relationships of this precursor cell population in spleen and bone marrow. The purpose of this study was to determine the number of CD34+ cells at these sites by applying immunohistochemistry and morphometry. In seven patients with IMF and a control group without hematopathology (14 patients), CD34+ progenitors were identified in the red pulp of the spleen and also in bone marrow trephine biopsies by the monoclonal antibody QBEND10. Histological analysis showed no differences regarding size or cytological details of these cells at both sites in patients with IMF as well as in the controls. On the other hand, in the IMF group there was an unequal distribution with an approximate twofold increase in precursor cells in the spleen compared to the bone marrow. This result is opposed to corresponding values of the control group. Considering the quantity of progenitor cells in the normal bone marrow, no significant increase was revealed in IMF, but a marked pooling (more than fourfold of the normal value) in the spleen. In conclusion, our findings are in keeping with a increased number of splenic CD34+ progenitor cells and therefore support the hypothesis of a pronounced filtration and trapping of this precursor cell population by the spleen in IMF.

Aged↗
PubMed2006

Survivin expression in "low-risk" and "high-risk" myelodysplastic syndromes.

Apoptosis has a crucial role in myelodysplastic syndromes (MDS), being responsible of the ineffective hematopoiesis characteristic of the disease. Apoptosis rate is elevated in "early phase" MDS, whereas it diminishes during disease progression to acute leukemia, consensually to the acquisition of independent growth features. Survivin is a member of the inhibitor of the apoptosis (IAP) family, with the bifunctional role of suppressing apoptosis while facilitating cell cycle progression. We investigated Survivin mRNA levels by real-time quantitative reverse transcriptase PCR analysis and Survivin protein expression by immunohistochemistry in 49 bone marrow (BM) aspirates and in 17 BM biopsies (BMB) from MDS patients. Survivin mRNA levels were higher in MDS than in control group (1.68 +/- 1.46 vs 0.25 +/- 0.22; p < 0.0001). MDS patients with low or INT1 International Scoring System for Evaluating Prognosis (IPSS) displayed higher levels of Survivin mRNA in comparison to INT2 or high IPSS (1.91 +/- 1.51 vs 0.88 +/- 0.95; p = 0.0058). Survivin protein immunoreactivity was evaluated as Survivin index S ((i)) and calculated according to the formula: S ((i)) = % of Survivin positive cells x BMB cellularity / 100. Survivin index was higher in the MDS group than in normal BM (p = 0.05). Moreover, in eight cases in which BM aspirates and trephine biopsy were available, we found a significant association between the level of Survivin mRNA and protein expression (p = 0.011). In conclusion, this study demonstrates increased levels of Survivin in MDS compared to normal controls. Moreover, higher levels of transcripts are related to "low-risk" MDS. Our results suggest an active role of Survivin in normal and in myelodysplastic hematopoiesis.

Adult↗
PubMed2001

Clinical and morphological criteria for the diagnosis of prefibrotic idiopathic (primary) myelofibrosis.

A clinicopathological study was performed to define initial-prefibrotic precursor stages of idiopathic (primary) myelofibrosis (IMF) by presenting laboratory and histological bone marrow features. Contrary to the usually accepted diagnostic requirements for IMF, including bone marrow fibrosis and a leukoerythroblastic blood picture, we found that 80 patients did not completely comply with these criteria. In particular, this cohort displayed no increase in the reticulin-collagen fiber content of the bone marrow at onset. Therefore, these cases were occasionally regarded as unclassifiable chronic myeloproliferative disorders (MPDs), or presumptively as essential thrombocythemia (ET). Patients were characterized by a certain set of clinical parameters comprising a borderline to slight leukocytosis and therapy-refractory anemia, minimal to modest splenomegaly, and often an elevated platelet count. Peripheral blood films revealed, only very sparsely, tear drop cells and a few erythroid and myeloid precursors, but no definite leukoerythroblastic reaction. Bone marrow histopathology was consistent with an increase in cellularity and a prominent left-shifted neutrophil granulopoiesis. Erythropoiesis disclosed a slight reduction with small to medium-sized islets. Megakaryopoiesis was the most prominent diagnostic hallmark to distinguish initial-prefibrotic IMF from the allied subtypes of MPDs. This cell lineage was not only characterized by a conspicuous growth and abnormal clustering, but also by a pronounced deviation from nuclear-cytoplasmic differentiation (dysplastic appearance). Cytological anomalies were compatible with a large variety of size and shape, ranging from giant- to atypical micromegakaryocytes with compact and bulky, cloud-like nuclei, due to a coarse lobulation and a frequent occurrence of naked (denuded) nuclei. Follow-up examinations, including sequential trephine biopsies in 22 patients, revealed a transition into myelofibrosis accompanied by laboratory findings in keeping with manifest IMF. In conclusion, morphological and clinical parameters have been validated by this study, which are consistent with a set of diagnostic criteria to recognize initial or prefibrotic precursor stages of IMF.

Adult↗
PubMedDate not supplied

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling.

In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics.

Acute Disease↗
PubMed2002

[Coincidence of chronic idiopathic myelofibrosis and chronic lymphocytic leukaemia. A rare phenomenon?].

In 1986 we diagnosed chronic idiopathic myelofibrosis (CIMF) in a 45-year-old asymptomatic patient with hepatosplenomegaly. In 1996 splenectomy was performed because of hypersplenism, and chemotherapy with hydroxyurea was initiated. In 1999 generalised lymphadenopathy of chronic lymphocytic leukaemia (B-CLL) developed. A trephine biopsy showed leukaemic bone marrow infiltration. On heteroduplex analysis we found a clonal rearrangement of IgH in the leukaemic lymphocytes. The coincidence of chronic myeloproliferative and lymphoproliferative diseases in the same patient is a rare phenomenon. According to the relevant literature, seven cases with a combination of CIMF/CLL have been reported. Possible pathomechanisms for the development of such coincidences are: 1) a bilineage manifestation of a pluripotent stem cell proliferation, 2) independent proliferations of two distinct cell lines under a common leukaemogenic stimulus or 3) an accidental association. These coincidence cases often showed a mild clinical course and also in our case, the patient is still alive and in a stable disease condition 16 years after the initial diagnosis.

Diagnosis, Differential↗
PubMed2006

[Hematological side effects of tyrosine kinase inhibition using imatinib].

Imatinib (STI571, Gleevec/Glivec) and other small-molecule tyrosine kinase inhibitors are highly effective in the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors and, for example, eosinophilia-associated chronic myeloproliferative disorders. This molecularly targeted approach disrupts abnormal tyrosine kinase dependent signalling pathways, thus providing a preferred treatment option for selected neoplastic disorders with activating mutations of Abelson-, Abl-related-, Kit-, and platelet-derived growth factor receptor A and B genes. Loss of response to imatinib may be due to an acquired resistance of emerging mutant tumor cell clones. Therapy is generally well tolerated. However, toxicities including edema, skin rashes, fatigue, nausea and myelosuppression have been reported. Philadelphia/Bcr-Abl-negative clonal chromosomal abnormalities may develop. Bone marrow trephines obtained from CML patients in complete remission with prolonged pancytopenia secondary to imatinib generally show marrow hypoplasia. Morphological features may be in keeping with either aplastic anemia or myelodysplasia developing in Philadelphia-negative hematopoiesis. Single or multilineage myelodysplasia may be accompanied by an excess of blasts and rarely evolves into acute leukemia in CML patients. Severe adverse hematological effects of imatinib are extremely rare. Current questions involve the molecular mechanisms of hematological side effects of tyrosine kinase inhibitors with special regard to the emergence of distinct aberrant clones.

Antineoplastic Agents↗