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Biomedical subjects

M Keating

Publications and source records attributed to M Keating.

At least 55 records · Page 3Linked to original sources
PubMed1999

Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia.

Vascular endothelial growth factor (VEGF) is a potent mitogen for vascular endothelial cells. It has been associated with angiogenesis, growth, dissemination, metastasis, and poor outcome in solid tumors. To assess cellular VEGF levels and their prognostic significance in newly diagnosed acute myeloid leukemia (AML), we used a radioimmunoassay (RIA) to quantify VEGF levels in stored samples obtained before treatment from 99 patients with newly diagnosed AML treated at the MD Anderson Cancer Center from 1996 to 1998. Outcome in the 99 patients was representative of that observed in all patients seen at this institution with this diagnosis during these years, but the 99 patients had higher white blood cell (WBC) and blast counts than the other patients. Results of the RIA were confirmed by Western blot. There was a relationship between increasing VEGF levels and shorter survival (P =.01), as well as shorter disease-free survival, both from start of treatment and from complete response (CR) date. In contrast, there was no relationship between VEGF level and WBC or blast count, or between VEGF level and such established prognostic factors as age, cytogenetics, performance status, or presence of an antecedent hematologic disorder, and multivariate analysis indicated that VEGF was still prognostic for the above outcomes after accounting for these factors, as well as treatment. Our results suggest that at least in AML patients with higher WBC and blast counts, cellular VEGF level is an independent predictor of outcome.

Acute Disease↗
PubMed1999

Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia.

BACKGROUND: L-asparaginase in combination with methotrexate has synergistic antileukemic activity in a schedule-dependent fashion. A new preparation of L-asparaginase, polyethylene-glycol conjugated (PEG)-asparaginase, is a pharmacologically different formulation of L-asparaginase with distinct properties including a longer half-life and less immunogenic properties. METHODS: Patients with refractory or recurrent acute lymphoblastic leukemia (ALL) were treated with a combination of methotrexate (MTX), vincristine, PEG-asparaginase, and prednisone (MOAP). The treatment was comprised of MTX, 100 mg/m(2) intravenously (i.v.), over 15 minutes on Days 1 and 14; PEG-asparaginase, 2500 IU/m(2), with a maximum dose of 3750 IU i.v. approximately 4-6 hours after MTX on Days 1 and 14; vincristine, 1.4 mg/m(2) (maximum dose, 2 mg) i.v., over 15 minutes on Days 1, 7, and 14; and prednisone, 200 mg daily orally, on Days 1-5 and 14-19. RESULTS: Thirty-two patients with a median age of 34 years (range, 20-74 years) were treated. Eight patients (25%) had ALL that was refractory to prior therapy and 24 patients (75%) had recurrent disease. Seven patients (22%) achieved a complete remission (CR). Five patients (16%) died early due to infections. Features associated with a poor response were high pretreatment lactate dehydrogenase levels and Philadelphia chromosome positive disease. The median duration of CR was 16 weeks and the overall median survival after MOAP therapy was 12 weeks. Anaphylactic reactions were not observed during MOAP combination therapy. CONCLUSIONS: MOAP is an active regimen in patients with refractory or recurrent ALL. This regimen is well tolerated and is not associated with allergic reactions. However, further studies regarding the pharmacologic interaction of MTX with PEG-asparaginase are needed to optimize this regimen.

Adult↗
PubMed1999

Molecular remissions induced by liposomal-encapsulated all-trans retinoic acid in newly diagnosed acute promyelocytic leukemia.

All-trans retinoic acid administered orally (oral ATRA) may not regularly lead to either molecular complete remissions (CRs) or prolonged hematologic CRs (HCR) unless combined with chemotherapy. Because serum tretinoin concentrations are higher, and maintained longer, after use of liposomal-encapsulated ATRA (lipoATRA) rather than oral ATRA, we investigated lipoATRA monotherapy in newly diagnosed acute promyelocytic leukemia (APL). Patients received lipoATRA 90 mg/m(2) every other day for remission induction. The same dose was given 3 times a week until 9 months had elapsed from HCR date. Treatment then stopped. Chemotherapy (idarubicin 12 mg/m(2) daily days 1-2 for 2 courses) was to be added only if 2 polymerase chain reaction (PCR) tests, performed 2 weeks apart, were positive at 3, 6, or 9 months from HCR date. The sensitivity level of the PCR was 10(-4). We treated 18 patients (median age, 54 years; median white blood cell [WBC] count 4,500/microL). The HCR rate was 12/18 (67%, 95% confidence interval [CI], 41% to 87%). This rate was similar to that we observed in a previous study using oral ATRA + idarubicin. Nine of 10 patients studied at HCR date were PCR-positive. Subsequently, however, overall (+/- idarubicin) rates of PCR positivity were 0/12 at 3 months, 1/10 at 6 months, 1/7 at 9 and 12 months, and 0/4 at 15 to 17 months. Idarubicin has been added in 3 patients, with this addition occurring at 6 months in 2 patients and at 9 months in 1 patient. Among patients who had not received idarubicin when the PCR was evaluated, 0 of 12 were PCR-positive at 3 months, 1 of 10 was positive at 6 months, 1 of 6 was positive at 9 months, 0 of 4 were positive at 12 months, and 0 of 3 were positive at 15 to 17 months. Morphologic APL has recurred in 1 patient, with a median follow-up time of 13 months in the 11 patients remaining in first CR. The median follow-up time is 91/2 months (range, 3 to 17) in the 9 patients who have received only lipoATRA and who remain PCR-negative and in first CR. Our data suggest that lipoATRA is an effective means of producing molecular CR in newly diagnosed APL.

Administration, Oral↗
PubMed1999

Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia.

Homoharringtonine (HHT) is a novel plant alkaloid that produced a complete hematologic remission (CHR) in 72% of patients with late chronic phase chronic myelogenous leukemia (CML). Cytogenetic (CG) remissions were noted in 31%. In this study, six courses of HHT were administered to 90 patients with early chronic phase CML (< 1 year from diagnosis). Patients then received interferon-alpha (IFN-alpha) with a target dose of 5 MU/m2 daily. Results were compared with those in a prior group of patients treated with IFN-alpha-based therapy between 1982 and 1990. Ninety-two percent of patients achieved CHR with HHT; CG responses were observed in 60% and were major in 27%. Both CHR and CG response rates were significantly higher than those seen in historical control patients after 6 months of IFN-alpha therapy. After receiving HHT, patients required lower doses of IFN-alpha to maintain a CHR. The median dose delivered was 2.4 MU/m2. This reduction in IFN-alpha dose was associated with a lower incidence of myalgia and gastrointestinal (GI) disturbances than that seen in patients treated at the 5 MU/m2 dose. Overall, CG responses were seen in 66% of the patients who received HHT and IFN-alpha compared with 61% of the historical control patients. HHT is a very effective treatment of early chronic phase CML, and ongoing trials are investigating the simultaneous administration of HHT and IFN-alpha, as well as that of HHT and low-dose cytosine arabinoside in patients failing IFN-alpha therapy.

Adult↗
PubMed1999

ATM mutations in B-cell chronic lymphocytic leukemia.

Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22-23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particularly, lymphoid tumors. A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22-23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22-23. Loss of heterozygosity at 11q22-23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL. To determine whether the ATM gene is altered in B-CLL, we have sequenced individual ATM exons in six B-CLL cases. We show that the ATM gene is mutated in a fraction of B-CLLs and that mutations can be present in the germ line of patients, suggesting that ATM heterozygotes may be predisposed to B-CLL.

Adult↗
PubMed1999

Correlation between lower c-mpl protein expression and favorable cytogenetic groups in acute myeloid leukemia.

The gene for the thrombopoietin receptor, c-mpl, has been shown to be overexpressed at the mRNA level in acute myeloid leukemia (AML) and myelodysplastic syndrome. A recent study reported c-mpl mRNA overexpression in 60% of a small sample of AML patients, and this overexpression correlates with shorter complete remission but not with karyotype group. We quantified c-mpl protein expression in 107 cases of AML and 24 normal bone marrow and 12 normal peripheral blood samples by using Western blot analysis and radioimmunoassay (RIA). Western blot analysis revealed no detectable level of c-mpl protein in the normal samples, whereas trace amounts were detected by RIA. c-mpl protein expression was increased (> or = twice normal) in 65% of the AML cases. c-mpl protein expression was correlated with cytogenetic groups (P = 0.0009, Kruskal-Wallis test in rejecting the hypothesis that c-mpl expression was the same in different groups). Specifically, patients with favorable cytogenetic groups (t(8;21), inv16, and t(15;17)) had lower c-mpl protein expression (median 1.7 times normal), whereas patients with unfavorable abnormalities (+8, -5 or -7, and del(11)(q23)) and normal cytogenetics had high expression (3.1 and 2.85 times normal, respectively). The findings were the same when only the 61 untreated AML patients were considered. No statistically significant correlation between c-mpl expression and age or antecedent hematologic disorder was found. These results suggest that c-mpl protein overexpression in AML may play a role in the aggressiveness of this disease.

Blotting, Western↗
PubMed1999

The prognostic significance of 13q14 deletions in chronic lymphocytic leukemia.

Although chronic lymphocytic leukemia (CLL) is the most common leukemia in adults, little is known about the molecular abnormalities underlying it and their prognostic significance. Using a battery of six microsatellite markers from 13q12.3-14.3 between BRACA2 gene and the Rb gene, we assayed loss of heterozygosity (LOH) in 78 CLL patients. We found deletion in 13q14 in 29 patients (37%) between D13S153 and the AFMa 301wb5. Classical cytogenetics was less sensitive, as it detected the 13q14 deletion in only one out of 69 patients (1%) in whom adequate metaphases were obtained. We found no significant difference in survival between patients with and patients without 13q14 LOH. In subset of patients with low beta2-microglobulin levels, those with 13q14 LOH had significantly shorter survival than did patients with low beta2-microglobulin levels but no 13q14 LOH. Also patients in early Rai stages (0-II) with 13q14 LOH had shorter survival period (P = 0.05) than did patients without LOH. These data confirm the prevalence of 13q14 deletion in CLL and suggest that this deletion may help identify more aggressive disease in patients presenting with early stage disease.

Adult↗
PubMed1999

Phase I study of liposomal daunorubicin in patients with acute leukemia.

The dose of anthracyclines used during induction has been identified as a significant prognostic factor in acute leukemias. Liposomal encapsulation of anthracyclines has been proposed as a way of decreasing toxicity and probably increasing efficacy of these agents, therefore allowing the exploration of high-dose anthracycline therapy in acute leukemias. We conducted a phase I study of liposomal daunorubicin (Daunoxome; DNX) in patients with refractory or relapsed acute leukemias. Patients received three daily doses of DNX at 75, 100, 150 or 200 mg/m2 on each cycle, to a total dose of 225, 300, 450, and 600 mg/m2, respectively. At least three patients were included at each dose level before escalating to the next level, and patients could receive more than one course at the next dose level. Twenty-four patients were included and 23 are evaluable. Fifteen patients received one course, seven received two courses, and one received three courses of DNX. Seventeen patients had previously received anthracyclines. The dose-limiting toxicity was mucositis which occurred (grade 3-4) in 3 of 5 patients treated at 200 mg/m2, 2 of 9 treated at 150 mg/m2 and 1 of 6 at 100 mg/m2. Other non-hematologic toxicity was mild and infrequent. There was no change in post-LVEF among 9 patients with available data and no significant cardiac events were documented. Two patients had a complete response: one patient with chronic myeloid leukemia in refractory blast phase went back to chronic phase, and one patient with second relapse acute promyelocytic leukemia achieved a third complete remission. We conclude that the maximally tolerated dose of DNX in this schedule is 150 mg/m2 and has significant anti-leukemia activity.

Acute Disease↗
PubMed1999

Deletions and losses in chromosomes 5 or 7 in adult acute lymphocytic leukemia: incidence, associations and implications.

Deletions or losses in chromosomes 5 or 7 are recurrent non-random abnormalities in acute myeloid leukemia (AML), and are associated with prior exposure to carcinogens or leukemogenic agents, and with poor prognosis. Their occurrence and significance in adult acute lymphocytic leukemia (ALL) is not well described. The aim of the study was to evaluate the incidence, associations and implications of chromosome 5 or 7 abnormalities in adult ALL. Patients with newly diagnosed ALL referred to MD Anderson Cancer Center between 1980 and 1996 were analyzed. Characteristics and outcome of patients with or without chromosome 5 or 7 abnormalities were compared by standard statistical methods. Thirty-one of 468 patients (6.6%) had chromosome 5 or 7 abnormalities. Loss of chromosome 5 occurred in six cases, three of them had both chromosome 5 and 7 abnormalities. Deletion or loss of chromosome 7 occurred as a single abnormality in three patients; in 28 patients it was associated with other abnormalities. The most significant cytogenetic association was with the Philadelphia chromosome (Ph) abnormality occurring in nine patients (29%). Compared with patients without the abnormalities, patients with chromosome 5 or 7 abnormalities tended to express CD34 more frequently (74% vs 54% P = 0.07), to be older (age >60 years 29% vs 18% P = 0.14), and to be associated with Ph (29% vs 11% P = 0.004). With therapy, the complete response (CR) rate with chromosome 5 or 7 abnormalities was lower (64% vs 79% P = 0.038) but the survival rate was similar (3-year survival rate 32% vs 36% P = 0.14). When the 22 patients without Ph were considered separately, the CR and survival rates were similar among patients with or without chromosome 5 or 7 abnormalities. Abnormalities in chromosome 5 or 7 are not specific for AML, and may occur in ALL. Unlike in AML, chromosome 5 or 7 abnormalities in ALL were not predictive of worse prognosis, which is accounted for mostly by the association with Ph.

Adolescent↗
PubMed1999

Use of peripheral blood blasts vs bone marrow blasts for diagnosis of acute leukemia.

Acute leukemia can be diagnosed when blasts constitute 30% or more of the nucleated cells in a patient's peripheral blood (PB) sample. To determine whether in such cases bone marrow (BM) aspirates are still necessary, we compared the results of diagnostic studies performed on PB samples with blast counts of 30% or more with those performed on the same patients' BM samples. We found no differences in morphologic features, cytochemistry, or immunophenotype between the blasts in PB and BM samples in any of 30 cases studied. However, in 10 (23%) of 44 cases in which cytogenetic analysis was performed, PB but not BM samples were insufficient for analysis. The converse never occurred. Five of the 10 cases had acute lymphoblastic leukemia and 5 had acute myeloid leukemia (41% of the patients with acute lymphoblastic leukemia and 17% of the patients with acute myeloid leukemia). In cases with adequate metaphases, there was strong correlation between the cytogenetic results for PB and BM samples. Some PB samples with blast counts of 30% or more are adequate for diagnosis of acute leukemia, especially when therapy can be delayed until it is known that an adequate number of analyzable metaphases are recovered from the PB samples.

Acute Disease↗
PubMed1999

De novo CD5+ Burkitt lymphoma/leukemia.

CD5 is a T-cell marker aberrantly expressed in B-cell chronic lymphocytic leukemia and mantle cell lymphoma. Other B-cell neoplasms, including Burkitt lymphoma, are usually CD5-. We report 4 cases of de novo CD5+ Burkitt lymphoma/leukemia in elderly patients, all of whom were in a leukemic phase and had variable lymph node and splenic involvement. The blasts were typically medium sized, with folded nuclei, distinct but not prominent nucleoli, and moderate amounts of somewhat vacuolated basophilic cytoplasm; they were terminal deoxynucleotidyl transferase--negative and surface immunoglobulin--positive. All 4 cases demonstrated c-myc rearrangement, but none had t(14;18), t(11;14), or cyclin D1 overexpression or rearrangement. Only 1 patient achieved complete remission after hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) therapy. One patient responded poorly to hyper-CVAD, and 2 patients died during induction chemotherapy. These rare cases of aggressive lymphoid malignancy with CD5 positivity and molecular features associated with Burkitt lymphoma/leukemia are best classified as Burkitt leukemia. However, the morphologic and immunophenotypic similarity to the blastoid variant of mantle cell lymphoma are diagnostically challenging. The diseases can be distinguished at the genetic level, since Burkitt lymphoma involves the rearrangement of c-myc, and mantle cell lymphoma usually the overexpression or rearrangement of cyclin D1.

Aged↗
PubMed1999

Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia.

PURPOSE: To evaluate the efficacy and safety of the combination of topotecan and cytarabine in patients with myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Fifty-nine patients with MDSs and 27 with CMML were enrolled. They were either previously untreated (66%) or had received only biologic agents (14%) or chemotherapy with or without biologic agents (20%). Treatment consisted of topotecan 1.25 mg/m(2) by continuous intravenous infusion daily for 5 days and cytarabine 1. 0 g/m(2) by infusion over 2 hours daily for 5 days. Prophylaxis included antibacterial, antifungal, and antiviral agents. At a median follow-up of 7 months, all 86 patients were assessable for response and toxicity. RESULTS: Complete remission (CR) was observed in 48 patients (56%; 61% with MDSs, 44% with CMML; P =.15). Similar CR rates were observed for patients with good-risk and poor-risk MDS (70% and 56%, respectively). The treatment effectively induced CR in patients with a poor-prognosis karyotype involving chromosomes 5 and 7 (CR, 71%) and secondary MDSs (CR, 72%). Fifty-four patients received one induction course, 25 patients received two, and the rest received more than two. The median number of continuation courses was two. The median overall duration of CR was 34 weeks (50 weeks for MDSs and 33 weeks for CMML). The median survival was 60 weeks for MDS and 44 weeks for CMML patients. CR and survival durations were longer in patients with refractory anemia with excess blasts (RAEB). Grade 3 or 4 mucositis or diarrhea was observed in three patients each. Fever was observed in 63%, and infections in 49% of patients. Six patients (7%) died during induction therapy. CONCLUSION: Topotecan and cytarabine induced high CR rates in unselected patients with MDSs and CMML, particularly among patients with poor-prognosis cytogenetics and secondary MDSs. Topotecan-cytarabine is an active induction regimen in MDS and CMML patients, is well tolerated, and is associated with a low mortality rate.

Adult↗
PubMed1999

Persistence of peripheral blood and bone marrow blasts during remission induction in adult acute lymphoblastic leukemia confers a poor prognosis depending on treatment intensity.

Our objectives were to evaluate the prognostic implications of persistence of peripheral blood blasts on day 7 (D7PBb) and of bone marrow blasts >5% on day 14 (D14Mb) after initiation of induction chemotherapy in adults with acute lymphoblastic leukemia (ALL) treated with two different chemotherapy regimens. Records of 365 consecutive newly diagnosed adult ALL patients treated with: (a) vincristine-, doxorubicin-, and dexamethasone-based chemotherapy (VAD, n = 219; 1984-1992); or (b) fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate/high-dose cytarabine (HCVAD, n = 146; 1993-1996), were analyzed. The complete remission (CR) rates were 73% with VAD and 91% with HCVAD (P<0.0001). Three-year event-free survival (EFS) rates were 23 and 40%, respectively (P = 0.00003). The impact of D7PBb and D14BMb on outcome varied with the induction regimen. Patients treated with VAD who had D7PBb had similar EFS rates compared with patients without D7PBb (P = 0.12), but EFS was inferior if they had persistent D14BMb compared with those patients without D14BMb (P = 0.00006). In HCVAD-treated patients, EFS was significantly worse in patients with persistent D7PBb (P = 0.003) but not in patients with D14BMb (P = 0.19). By multivariate analysis, D14BMb was an independent adverse feature for patients treated with VAD, whereas D7PBb was an independent adverse feature for EFS in HCVAD-treated patients. Early clearance of leukemia cells from blood and bone marrow is associated with improved outcome in adult ALL, but the prognostic significance of D7PBb and D14BMb clearance varies with treatment efficacy.

Adolescent↗
PubMed1999

A phase II trial of docetaxel (Taxotere) in hormone-refractory prostate cancer: correlation of antitumor effect to phosphorylation of Bcl-2.

Twenty-one patients with hormone refractory prostate cancer were enrolled to receive single-agent docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) 75 mg/m2 intravenously every 21 days. Six patients consented to biopsies of the prostate tumor before and following the first cycle of chemotherapy and 11 patients underwent periodic blood collection for isolation of the mononuclear cell fraction. The toxicities of treatment were moderate but included eight episodes of grade III and two episodes of grade IV nonhematologic toxicity as well as seven episodes of grade III and 11 episodes of grade IV hematologic toxicity (primarily neutropenia, including four episodes of febrile neutropenia). An objective response of more than 50% reduction in prostate-specific antigen was observed in seven patients (38%) and more than half of the patients with symptomatic disease at the initiation of therapy had improvements on treatment. Radiographic or scintigraphic evidence of tumor regression was observed in six patients. Nine patients experienced a prolonged period of stable disease on treatment (median, six cycles). Tumor specimens are currently being analyzed for bcl-2 expression and phosphorylation. The current series confirms the substantial single-agent activity of docetaxel in hormone refractory prostate cancer and may help to further elucidate its mechanism of action at the molecular level.

Aged↗
PubMed1998

Proteasome inhibitors induce apoptosis in glucocorticoid-resistant chronic lymphocytic leukemic lymphocytes.

Our previous work showed that the nuclear scaffold (NS) protease is required for apoptosis of both thymocytes and chronic lymphocytic leukemic (CLL) lymphocytes. Because partial sequencing of one of the subunits of the NS protease revealed homology to the proteasome, we tested the effects of classical proteasome inhibitors on apoptosis in CLL cells. Here we report that proteasome inhibition caused high levels of DNA fragmentation in all patients analyzed, including those resistant to glucocorticoids or nucleoside analogs, in vitro. Proteasome inhibitor-induced DNA fragmentation was associated with activation of caspase/ICE family cysteine protease(s) and was blocked by the caspase antagonist, zVADfmk. Analysis of the biochemical mechanisms involved showed that proteasome inhibition resulted in mitochondrial dysregulation leading to the release of cytochrome c and a drop in mitochondrial transmembrane potential (triangle upPsi). These changes were associated with inhibition of NFkappaB, a proteasome-regulated transcription factor that has been implicated in the suppression of apoptosis in other systems. Together, our results suggest that drugs that target the proteasome might be capable of bypassing resistance to conventional chemotherapy in CLL.

Apoptosis↗
PubMed1998

Deficiency of the ATM protein expression defines an aggressive subgroup of B-cell chronic lymphocytic leukemia.

The gene mutated in ataxia telangiectasia, ATM, on human chromosome 11q22-q23 is implicated in cell cycle control and DNA repair. Ataxia telangiectasia patients as well as ATM-deficient mice are immune deficient and develop lymphoproliferative disease. Abnormalities in 11q22.3-q23.1 have also been described in B-cell chronic lymphocytic leukemia (B-CLL). We analyzed B-CLL samples for loss of heterozygosity (LOH) using microsatellite markers located at the ATM (D11S2179), mixed-lineage leukemia (MLL; D11S1356), and BCL1 (D11S987) loci, all of which are located around 11q23. Five (14%) of 36 informative cases showed LOH at the ATM gene, and two of these five cases had LOH at the MLL gene. No LOH was detected at the BCL1 locus, and none of the cases showed LOH at the MLL gene without LOH at the ATM gene. Four of these five cases with LOH at the ATM gene were studied for ATM protein expression by Western blot analysis. All four cases lacked ATM protein. An additional 111 cases of B-CLL were studied for expression of ATM protein by Western blot analysis and RIA. Thirty-eight (34%) of these cases showed ATM levels <50% of that seen in normal lymphoid cells. No morphological or immunophenotypic difference was observed between ATM-deficient B-CLL cases and cases with normal ATM expression. However, patients with ATM deficiency had significantly shorter survival times (35.66 versus 97.3 months; P = 0.003) and more aggressive disease, suggesting that ATM is involved in the leukemogenesis of B-CLL. These data also suggest that the ATM gene may play a role in the reported 11q23 abnormality in B-CLL, which also characterizes an aggressive disease.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1998

Comparison of referring and tertiary cancer center physician's diagnoses in patients with leukemia.

PURPOSE: To analyze the rates of concordance in the diagnosis of various hematological malignancies among patients referred to a tertiary cancer center, comparing the referring diagnosis with the final diagnosis at the M.D. Anderson Cancer Center. PATIENTS AND METHODS: This was a cross-sectional study analyzing the 409 patients referred to the M.D. Anderson Leukemia Service in 1995 in whom a bone marrow examination was performed by the referring physician and in whom this examination was repeated at our institution. We also analyzed 100 cases, including 84 of the 409 referred patients for whom the diagnostic outside bone marrow slide had been sent for review. RESULTS: The overall concordance rate was 73%. In 18% discordances were present and considered of major importance (affecting treatment and/or prognosis) while in 9% there were minor discordances. Major discordance rates were 2% for chronic lymphocytic leukemic leukemia and 5% for chronic myelogenous leukemia, but 29% for acute myelogenous leukemia (79 patients), 43% for acute promyelocytic leukemia (7 patients), 19% for acute lymphocytic leukemia (42 patients), 57% for hairy cell leukemia (7 patients), and 23% for the myelodysplastic syndromes (75 patients). The concordance rate was 76% in the 100 cases in which bone marrow specimens permitted comparison of the morphologic diagnosis made by M.D. Anderson and the referring physician using the same slide, with a rate of 75% in the acute leukemias as finally diagnosed at our institution. CONCLUSION: Although in the majority of cases the referring physicians and the specialty service agreed on diagnosis, major discordance occurs in a significant number of cases, including highly treatable diseases such as acute promyelocystic leukemia and hairy cell leukemia.

Bone Marrow↗