PubMed Health⌕ Search

Biomedical subjects

M Keating

Publications and source records attributed to M Keating.

At least 19 recordsLinked to original sources
PubMed2000

Deletions in the 13q14 locus in adult lymphoblastic leukemia: rate of incidence and relevance.

BACKGROUND: A putative tumor suppressor gene involved in chronic lymphocytic leukemia (CLL) has been localized to the 13q14 locus. Microsatellite analysis was used to test whether this locus also is involved in acute lymphoblastic leukemia (ALL) and its prognostic relevance determined. METHODS: The authors analyzed 49 patients with adult ALL for deletions at the 13q14 locus using a battery of 6 microsatellite markers corresponding to this region (D13S260, STR257, D13S263, D13S153, D13S319, and AFMa301wb5). RESULTS: Five of the 49 adult ALL patients analyzed (10%) showed loss of heterozygosity (LOH) or deletions at 13q14. Similar to CLL, the significant minimal deletions appeared to be localized between D13S260 and AFMa301wb5 and did not involve the retinoblastoma or BRCA2 genes. Among newly diagnosed patients, LOH was associated with shorter survival (P = 0.007). CONCLUSIONS: These data suggest that the 13q14 gene, commonly deleted in CLL patients, also is deleted in some patients with adult ALL. Although the number of the cases in the current study is small, 13q deletions in ALL patients may play a role in the clinical behavior of this disease.

Adult↗
PubMed2000

ATM gene deletion in patients with adult acute lymphoblastic leukemia.

BACKGROUND: Loss of heterozygosity (LOH) at the ATM gene (mutated in ataxia telangiectasia [AT] patients) and ATM protein deficiency occur in 14% and 34%, respectively, of patients with chronic lymphocytic leukemia (CLL). ATM protein deficiency also is associated with aggressive disease and worse patient survival. Considering the aberrations in the ATM gene in CLL and the high rate of incidence of lymphoid neoplasias in AT patients, the authors investigated its incidence rate and significance in patients with adult acute lymphoblastic leukemia (ALL). METHODS: Samples from 36 adults with ALL were analyzed for LOH and homozygous deletion (HD) using a panel of three microsatellite markers located at the ATM gene (D11S2179), the MLL gene (D11S1356), and the BCL1 gene (D11S987) loci. These markers are located within the 11q13-q23 locus. RESULTS: Of the 36 informative cases, 10 (28%) showed deletions (7 LOH and 3 HDs) at the D11S2179 marker. In two patients, the deletions were extended to the MLL gene locus. These deletions were submicroscopic because only 3% (1 of 36) of patients showed abnormalities involving 11q23 using cytogenetic studies. The authors also estimated the levels of ATM protein in 15 ALL patients and 12 healthy volunteers by radioimmunoassay. The ATM protein levels in cases with LOH at the ATM gene were between 15-50% of those from normal bone marrow. In contrast to CLL patients, patients with LOH or HD at the ATM gene locus showed better survival compared with patients without ATM gene deletions (P = 0.003). CONCLUSIONS: LOH of the ATM gene and protein deficiency are common in adult ALL, are not demonstrated at the cytogenetic level, and are associated with a favorable prognosis. The authors speculate that ATM deficiency may increase the sensitivity of leukemic blasts to the chemotherapy used during induction and after disease remission in patients with adult ALL. The relatively high frequency of deletion of the D11S2179 marker compared with the D11S1356 marker suggests that ATM is the target gene of the deletion at the 11q23 locus, and that such deletions may play a role in the pathogenesis of ALL.

Adult↗
PubMed2000

Variations in the low levels of cyclin D1/BCL1 have prognostic value in chronic lymphocytic leukemia.

Cyclin D1 (CyD1)/BCL1 (PRAD1) is expressed at high levels in almost all cases of mantle cell leukemia/lymphoma (MCL) and in rare cases of chronic lymphocytic leukemia (CLL). The CyD1/BCL1 protein plays an important role in the progression of cells through the G1 phase of cell cycle. Most of the CyD1/BCL1 protein expression studies are performed using immunohistochemistry. We used a sensitive solid-phase radioimmunoassay (RIA) to quantify CyD1 protein expression in 199 patients with CLL. Of these 137 patients were previously untreated with the rest having had standard chemotherapeutic regimens including alkylating agents and fludarabine before being referred to our center. Median white cell count in these patients was 49x10(3) /microl (range 3.0-438.5x10(3)/microl), hemoglobin level 13.1 g/dl (range 5.2-17.3 g/dl), platelet count 157x10(3) /microl (range 10-377x10(3) /microl), age 58 (range 26-89), and beta2-microglobulin 2.75 mg/dl (range 1.1-14.3). The median radioactivity (CPM) of mononuclear cells obtained from 56 normal individuals was assigned a value of 1. There was no significant variation in CyD1 levels among normal individuals (SD=0. 12). While most CyD1 levels in MCL varied from 6.5 to 15.6, the median CyD1/BCL1 in CLL was 1.4 with 75th percentile under 2.12. Rare CLL cases (3.5%) showed levels between 4 and 8.83. When divided into two groups at the median level, patients with higher CyD1/BCL1 expression had shorter survival (P = 0.03). This remained true when applied only to the previously untreated patients (P=0.05). Despite the relatively low expression, the CyD1/BCL1 levels in univariate analysis were as good or better predictors of survival than Binet (P = 0.03) or Rai (P = 0.05) staging. Furthermore, CyD1/BCL1 levels correlated with serum beta2-microglobulin (P = 0.001), white blood cell count (P = 0.004) and hemoglobin levels at the time of collection (P = 0.0003) but not with lymphocyte count, platelet count or age. The data demonstrate that CyD1/BCL1 is likely to play a significant role in the biology of CLL and can be used as a prognostic indicator. Further studies to clarify the role of CyD1 in the biology of CLL and its value as a prognostic indicator at the time of diagnosis are encouraged.

Adult↗
PubMed2000

Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia.

Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergistic activity with DNA damaging agents such as cyclophosphamide, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n=12) or relapsed (n=40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n=3, relapsed n=8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (HI; met all criteria for CR except for platelets < 100x10(9)/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%), and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.

Acute Disease↗
PubMed2000

Terminal deoxynucleotidyl transferase-negative acute lymphoblastic leukemia.

OBJECTIVE: Terminal deoxynucleotidyl transferase (TdT) is a useful marker in the diagnosis of acute lymphoblastic leukemia (ALL) (French-American-British [FAB] L1 and L2) and is most useful in distinguishing ALL from mature B-lymphoid neoplasms, such as Burkitt lymphoma (FAB L3) and other lymphoid malignancies. The frequency of TdT-negative ALL is not known. Here we report 3 TdT-negative ALL cases that met the criteria for T-cell ALL. DESIGN: We reviewed approximately 200 cases of ALL retrieved from the database at our institution. All cases were evaluated using Wright-Giemsa, myeloperoxidase, butyrate, and TdT staining; immunophenotyped using flow cytometry; and studied using Southern blot analyses for T-cell receptors and immunoglobulin gene rearrangement. RESULTS: All ALL cases (L1 and L2) were TdT-positive, except for 3 cases that were of early T-cell lineage. None of the 3 cases demonstrated positivity for TdT in immunofluorescence staining with polyclonal antibodies or flow cytometry with monoclonal antibodies. Flow cytometric analysis confirmed a pre-T-cell immunophenotype in all 3 cases. One of the cases showed rearrangement of a T-cell antigen receptor and immunoglobulin heavy chain (J(H)). A second case showed germline configuration of T-cell receptors, but also showed rearrangement of the J(H), despite the expression of T-cell markers only.

Adult↗
PubMed1999

A phase I-II trial of escalating doses of mitoxantrone with fixed doses of cytarabine plus fludarabine as salvage therapy for patients with acute leukemia and the blastic phase of chronic myelogenous leukemia.

BACKGROUND: Cytarabine is an essential drug for inducing remission of acute myelogenous leukemia, and it is also one the most effective drugs used as salvage therapy for patients with all types of relapsed acute leukemia. Nevertheless, there is considerable room for improvement in the treatment of patients with relapsed leukemia in terms of both the reinduction rate and the duration of response. Fludarabine has been shown to augment responses to cytarabine, possibly by increasing the intracellular concentrations of the active metabolite cytarabine triphosphate. Higher-than-standard doses of mitoxantrone have been shown to augment responses to cytarabine, possibly by increasing the DNA strand breaks induced by topoisomerase II; these strand breaks cannot be effectively repaired in the presence of cytarabine triphosphate. This preliminary study was designed to determine whether moderately high doses of mitoxantrone could be added to the combination of fludarabine and cytarabine in an attempt to improve the combination's antileukemic efficacy. METHODS: Fifty-five adults with relapsed or refractory acute leukemia or the blastic phase of chronic myelogenous leukemia (CML) received salvage therapy with the FLAM regimen, which consisted of fludarabine, cytarabine, and increasing doses of mitoxantrone. RESULTS: Even with doses of mitoxantrone escalated to as much as 60 mg/m(2) over 4 days, dose-limiting toxicity was not observed. Overall, the complete response rate was 27.3% (15 of 55 patients, including 4 of 17 with acute myelogenous leukemia [AML], 4 of 12 with acute lymphocytic leukemia [ALL], and 7 of 26 with the blastic phase of CML). The median time to complete response was 42 days. Toxicity other than myelosuppression was manifested primarily as hyperbilirubinemia, which was reversible in all cases. Poor performance status and undifferentiated blastic phase of CML were poor prognostic factors for response to FLAM. CONCLUSIONS: The FLAM regimen is an active salvage regimen and should be formally evaluated in Phase II studies of patients with AML, ALL, and the myeloid and lymphoid blastic phases of CML.

Adolescent↗
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↗