Biomedical subjects

Emili Montserrat

Publications and source records attributed to Emili Montserrat.

At least 19 recordsLinked to original sources

PubMed2006

Case-control comparison of at-home to total hospital care for autologous stem-cell transplantation for hematologic malignancies.

PURPOSE: One of the most significant limitations of at-home autologous stem-cell transplantation (ASCT) is the necessity for hospital readmission. We developed an at-home ASCT program in which prophylactic ceftriaxone and treatment of febrile neutropenia with piperacillin and tazobactam was introduced to minimize the readmission rate. PATIENTS AND METHODS: Between November 2000 and February 2005, 178 consecutive patients underwent ASCT for a hematologic malignancy. Of these, 50 patients fulfilled the requirements for at-home ASCT. Results were compared with those observed in a control group of 50 patients individually matched to the group of patients treated at home for age, sex, diagnosis, stage of disease, conditioning, and source of stem cells. RESULTS: Febrile neutropenia occurred in fewer patients in the at-home group as compared with the hospitalized group (76% v 96%: P = .008), and duration of fever was also shorter in the at-home group (median, 2 and 6 days, respectively; range, 1 to 11 and 1 to 20 days, respectively; P = .00003). Hospital readmission in the at-home group was required in only four cases (8%). This resulted in a reduction of 18.6 days of hospitalization per patient. Likewise, total median charges were approximately half in the at-home group as compared with the in-hospital group (3,345 euro v 6,250 euro, respectively; P < .00001). CONCLUSION: Results of at-home ASCT with prophylactic administration of ceftriaxone and domiciliary treatment of febrile neutropenia with piperacillin and tazobactam are highly satisfactory and significantly cheaper compared with those obtained with conventional in-hospital ASCT.

Adult↗

PubMed2006

Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations.

The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered "confirmed." The remaining subsets comprised pairs of sequences and were considered "potential"; public database CLL sequences were found to be members of 9 of 22 "potential" subsets, thereby allowing us to consider them also "confirmed." The chance of belonging to a subset exceeded 35% for unmutated or selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public database sequences showed that HCDR3 restriction is "CLL-related." CLL cases with selected stereotyped immunoglobulins (IGs) were also found to share unique biologic and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients.

ADP-ribosyl Cyclase 1↗

PubMed2006

Clinical implications of ZAP-70 expressionin chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a disease with an extremely heterogeneous prognosis. Because of this and because of the lack of a truly effective therapy, treatment of CLL must be adapted to the individual risk of each patient. Over the last quarter of century, prognosis of patients with CLL has been based on clinical features. In the last few years a number of biological prognostic parameters have been identified. Among them, the expression of ZAP-70 in neoplastic B lymphocytes is increasingly being recognized as of paramount importance to predict outcome. Patients with a low percentage (<20%) of ZAP-70 positive neoplastic B lymphocytes have a much better prognosis that those with a higher proportion (>20%) of ZAP-70 positive neoplastic B lymphocytes.

Biomarkers, Tumor↗

PubMed2006

Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression.

Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) is an infrequent leukemia subtype with characteristic clinicobiological features. This translocation leads to fusion of MYST3 (MOZ) and CREBBP (CBP) genes, probably resulting in a disturbed transcriptional program of a myelomonocytic precursor. Nonetheless, its gene expression profile is unknown. We have analyzed the gene expression profile of 23 AML patients, including three with molecularly confirmed MYST3-CREBBP fusion gene, using oligonucleotide U133A arrays (Affymetrix). MYST3-CREBBP cases clustered together and clearly differentiated from samples with PML-RARalpha, RUNX1-RUNX1T1, and CBFbeta-MYH11 rearrangements. The relative expression of 46 genes, selected according to their differential expression in the high-density array study, was analyzed by low-density arrays in an additional series of 40 patients, which included 7 MYST3-CREBBP AML cases. Thus, genes such as prolactin (PRL) and proto-oncogene RET were confirmed to be specifically overexpressed in MYST3-CREBBP samples whereas genes such as CCND2, STAT5A, and STAT5B were differentially underexpressed in this AML category. Interestingly, MYST3-CREBBP AML exhibited a characteristic pattern of HOX expression, with up-regulation of HOXA9, HOXA10, and cofactor MEIS1 and marked down-regulation of other homeobox genes. This profile, with overexpression of FLT3, HOXA9, MEIS1, AKR7A2, CHD3, and APBA2, partially resembles that of AML with MLL rearrangement. In summary, this study shows the distinctive gene expression profile of MYST3-CREBBP AML, with overexpression of RET and PRL and a specific pattern of HOX gene expression.

Acute Disease↗

PubMed2006

High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma.

The tumor microenvironment plays an important role in the biologic behavior of follicular lymphoma (FL), but the specific cell subsets involved in this regulation are unknown. To determine the impact of FOXP3-positive regulatory T cells (Tregs) in the progression and outcome of FL patients, we examined samples from 97 patients at diagnosis and 37 at first relapse with an anti-FOXP3 monoclonal antibody. Tregs were quantified using computerized image analysis. The median overall survival (OS) of the series was 9.9 years, and the FL International Prognostic Index (FLIPI) was prognostically significant. The median Treg percentage at diagnosis was 10.5%. Overall, 49 patients had more than 10% Tregs, 30 between 5% to 10%, and 19 less than 5%, with a 5-year OS of 80%, 74%, and 50%, respectively (P = .001). Patients with very low numbers of Tregs (< 5%) presented more frequently with refractory disease (P = .007). The prognostic significance of Treg numbers was independent of the FLIPI. Seven transformed diffuse large B-cell lymphomas (DLBCLs) had lower Treg percentages (mean: 3.3%) than FL grades 1,2 (mean: 12.1%) or 3 (mean: 9%) (P < .02). In conclusion, high Treg numbers predict improved survival of FL patients, while a marked reduction in Tregs is observed on transformation to DLBCL.

Aged↗

PubMed2006

Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy.

PURPOSE: To determine the methylthioadenosine phosphorylase (MTAP) gene alterations in mantle cell lymphoma (MCL) and to investigate whether the targeted inactivation of the alternative de novo AMP synthesis pathway may be a useful therapeutic strategy in tumors with inactivation of this enzyme. EXPERIMENTAL DESIGN: MTAP gene deletion and protein expression were studied in 64 and 52 primary MCL, respectively, and the results were correlated with clinical behavior. Five MCL cell lines were analyzed for MTAP expression and for the in vitro sensitivity to L-alanosine, an inhibitor of adenylosuccinate synthetase, and hence de novo AMP synthesis. RESULTS: No protein expression was detected in 8 of 52 (15%) tumors and one cell line (Granta 519). Six of these MTAP negative tumors and Granta 519 cell line had a codeletion of MTAP and p16 genes; one case showed a deletion of MTAP, but not p16, and one tumor had no deletions in neither of these genes. Patients with MTAP deletions had a significant shorter overall survival (mean, 16.1 months) than patients with wild-type MTAP (mean, 63.6 months; P < 0.0001). L-Alanosine induced cytotoxicity and activation of the intrinsic mitochondrial-dependent apoptotic pathway in MCL cells. 9-beta-D-Erythrofuranosyladenine, an analogue of 5'-methylthioadenosine, selectively rescued MTAP-positive cells from L-alanosine toxicity. CONCLUSIONS: MTAP gene deletion and lack of protein expression are associated with poor prognosis in MCL and might identify patients who might benefit from treatment with de novo AMP synthesis pathway-targeted therapies.

Base Sequence↗

PubMed2006

Darbepoetin-alpha for the anaemia of myelofibrosis with myeloid metaplasia.

Darbepoetin-alpha, a novel hyperglycosylated erythropoiesis-stimulating protein, was administered to 20 patients with myelofibrosis with myeloid metaplasia and anaemia. The initial weekly dose, 150 mug, was increased to 300 mug when no response was observed after 4-8 weeks. Eight patients (40%) responded to treatment, including six complete and two partial responses, and five maintained their response at a median follow-up of 12 months (range 4-22). Univariate analysis indicated that older age was the only factor associated with a favourable response to treatment (P = 0.006). None of the patients with appropriate serum erythropoietin levels responded. Treatment was usually well tolerated.

Adult↗

PubMed2006

Clinical factors influencing T-cell receptor excision circle (TRECs) counts following allogeneic stem cell transplantation in adults.

To ascertain the clinical factors involved in T-cell reconstitution after allogeneic stem cell transplantation (SCT), we evaluated serial assessments of lymphocyte subsets by flow cytometry and TRECs levels by quantitative PCR in 83 adult patients. Patient age >25 years, unrelated donor, CMV infection and acute graft-versus-host disease (GVHD) adversely affected CD3(+) and CD8(+) T-cell recovery after SCT (p < 0.05). TRECs were low or undetectable during the first months after transplant and progressively increased thereafter. However, median TRECs of patients did never achieve normal values compared to healthy donors (median follow-up 9 months, range 2-42). Presence and severity of chronic GVHD significantly affected TRECs counts: patients with chronic GVHD had lower TRECs than patients without GVHD at 9, 12 and 24 months after SCT (p = 0.002, p = 0.022, p = 0.015). Patients with limited chronic GVHD had higher TRECs compared to patients with extensive GVHD (p = 0.018). No relationship was observed between fungal or bacterial infections and TRECs. Nonetheless, CMV infection was associated with lower TRECs (p = 0.032). Our data support the concept that adult thymus contributes with a slow but continuous production of thymic T cells to immune reconstitution after SCT. Chronic GVHD is the main factor associated to a delay in TRECs counts recovery.

Adult↗

PubMed2006

Bortezomib: an effective agent in extramedullary disease in multiple myeloma.

Bortezomib is a potent and selective proteasome inhibitor recently introduced in the treatment of multiple myeloma (MM). This drug produces significant responses in about one-third of patients with relapsed/refractory disease. We first recognized the lack of efficacy of thalidomide in soft-tissue plasmacytomas. There is little information on the effect of bortezomib on extramedullary myeloma. Four of 23 patients treated with bortezomib at our institution had extramedullary involvement at the time of relapse. In three of these patients large soft-tissue plasmacytomas disappeared. This indicates that bortezomib may be useful in clinical situations of extramedullary disease in which other agents, such as thalidomide, may not be effective.

Aged↗

PubMed2006

Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia.

Current prognostic factors for acute myeloblastic leukemia (AML) are not sufficient to accurately predict the group of patients in the intermediate-risk category who will successfully respond to treatment. Distinct patterns of inherited functional genomic polymorphisms might explain part of these heterogeneous prognoses. We used the allelic discrimination method to identify polymorphisms in GSTT1, SULT1C2, CDA, SXR (drug metabolic pathways), XPD, XPA, XPG, ERCC1, TOP2A (DNA repair), VEGF (angiogenesis), and MDR1 (multidrug resistance) genes in 110 adult patients with intermediate-risk AML, enrolled in the CETLAM-99 prospective trial. A multivariate prognostic model adjusted for age, white blood cell (WBC) count, French-American-British group, cytogenetics, MLL rearrangement, internal tandem duplication of FLT3 (FLT3-ITD), induction courses to achieve complete remission, and germline polymorphisms, was used to detect independent risk factors associated with clinical outcome. This analysis showed an increased risk of refractoriness to chemotherapy in the group of patients with XPA variant alleles (RR = 14; P = .02). In the same model, increased relapse risk was associated with SULT1C2 heterozygosity (RR = 4.1; P = .004), FLT3-ITD (RR 3.3; P = .003), and MDR1 variant alleles (RR = 2.4; P = .02). Adverse prognostic variables for overall survival were XPA (RR = 3.4; P = .02) and MDR1 (RR = 2.1; P = .02) variant alleles, and WBC count (RR = 2.1; P = .02). These findings might be useful in selecting risk-adapted treatment strategies in intermediate-risk AML.

Adult↗

PubMed2006

ZAP-70 expression in normal pro/pre B cells, mature B cells, and in B-cell acute lymphoblastic leukemia.

PURPOSE: The ZAP-70 gene is normally expressed in T and natural killer cells, where it is required for the T-cell receptor (TCR) signaling. More recently, it has been described that ZAP-70 contributes to the B-cell development at early stages of B-cell differentiation in mice. The purpose was to investigate the presence of ZAP-70 in normal pro/pre B cells and mature B cells and in tumoral cells from B-acute lymphoblastic leukemias (B-ALL). EXPERIMENTAL DESIGN: ZAP-70 expression was ascertained by flow cytometry, immunofluorescence, Western blot, and quantitative reverse transcription-PCR. Analysis of ZAP-70 and other signaling proteins of the pre-TCR/TCR was done by Western blot. RESULTS: ZAP-70 was expressed in pro/pre B cells but not in normal mature B cells derived from bone marrow, peripheral blood, or tonsil. Among tumoral cells, ZAP-70 was expressed in 56% of B-ALLs with pro/pre B-cell phenotype and in 4 of 6 Burkitt/ALL lymphomas. In B-ALL cells, expression of CD38 protein correlated with ZAP-70 expression (P = 0.05). Mutational analysis of the ZAP-70 gene revealed the absence of mutations in cases lacking ZAP-70 expression. Moreover, other elements of the pre-TCR/TCR signaling pathway, like LAT and Lck, were also found in B-ALL cells. CONCLUSIONS: Among normal B-cell subsets, ZAP-70 was found expressed in normal pro/pre B cells but not in a significant proportion of normal B cells with mature phenotype. Moreover, the presence of ZAP-70 in B-ALLs probably reflects their cellular origin. The lack of ZAP-70 expression in normal mature B cells suggests that its expression in mature-derived neoplasms with different cellular origin, such as Burkitt's lymphoma and chronic lymphocytic leukemia, might be due to an aberrant phenomenon.

Adolescent↗

PubMed2006

Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia.

We analyzed minimal residual disease (MRD) by consensus polymerase chain reaction (PCR), quantitative PCR (qPCR), and flow cytometry in 40 patients with chronic lymphocytic leukemia (CLL) who underwent stem cell transplantation; 97.4%, 89%, and 100% of the patients could be studied by consensus PCR, qPCR, and flow cytometry, respectively. Overall, 164 of 248 samples were negative for MRD by consensus PCR. Among those, CLL cells were detected by qPCR and by flow cytometry in 77 (47%) and 39 (23%) of the 164 samples, respectively. All 84 samples positive on PCR had detectable CLL cells by qPCR and flow cytometry. A good correlation was seen between MRD levels by flow cytometry and by qPCR (n = 254; r = 0.826; P < .001). Fifteen of 25 patients receiving autografts suffered a relapse, with increasing levels of MRD being observed before relapse in all of them. MRD detection within the first 6 months after autologous transplantation identified patients with a high relapse risk. In contrast, in allografted patients (n = 15) MRD did not correlate with outcome. In conclusion, quantitative methods to assess MRD (flow cytometry and qPCR) are more accurate than consensus PCR to predict clinical evolution. These results might be useful to investigate treatments aimed at preventing relapse in patients with CLL who have received an autograft.

Adult↗

PubMed2006

IGHV gene insertions and deletions in chronic lymphocytic leukemia: "CLL-biased" deletions in a subset of cases with stereotyped receptors.

Nucleotide insertions/duplications or deletions in immunoglobulin heavy chain genes have been found in 24/760 patients (3.15%) with chronic lymphocytic leukemia (CLL). In 21/24 cases, the inserted/duplicated or lost nucleotides occurred in multiples of 3; therefore, the original reading frame was maintained and a potentially intact receptor was coded. The pattern and location of insertions/duplications or deletions in CLL and their restriction to mutated IGHV rearranged genes strongly suggests that they resulted from somatic hypermutation. Their incidence in CLL is consistent with previous reports in normal, auto-reactive and neoplastic human B cells, thus seemingly indicating that these modifications generally arise without any particular disease-specific associations. A striking exception to this rule was identified in CLL IGHV3-21-expressing cases: one amino acid was deleted from the CDR2 region in 16/63 (25.4%) mutated CLL IGHV3-21 sequences (including public database-derived IGHV3-21 CLL cases + the present series) vs. only 2/257 (0.78%) public database-derived mutated non-CLL IGHV3-21 sequences; 15/16 CLL IGHV3-21 sequences carrying this deletion belonged to a subset with unique, shared HCDR3 and light chain CDR3 motifs. This finding further supports the idea of selective antigenic pressures playing a pathogenetic role in some CLL cases.

Amino Acid Sequence↗

PubMed2006

Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation.

OBJECTIVE: The Mannan-binding lectin (MBL) pathway involves recognition of fungal surfaces by MBL and cleavage of C2 and C4 by MBL-associated serine protease (namely, MASP-2). Recent data show that MBL pathway deficiency might result not only from polymorphisms of the MBL2 gene but also of MASP2. The aim of the study was to assess whether polymorphisms of these genes are associated with invasive fungal infections (IFIs) following allogeneic stem cell transplantation (allo-SCT). METHODS: The promoter and the exon 1 of MBL2 and the exon 3 of MASP2 were sequenced in 106 donor-recipient pairs from HLA-identical sibling allo-SCTs performed in a single institution. RESULTS: Ten percent of the donors and 11% of the recipients carried the MBL-low (O/O, LXA/O) genotypes; 7% of the donors and 3% of the recipients were heterozygous for the MASP2 Asp105Gly variant. Factors associated with a higher probability of IFIs were donor's MBL-low genotype (38% vs 12%, p = 0.01), recipient's MASP2 variant (67% vs 14%, p = 0.01), and acute graft-versus-host disease (GVHD) grades II to IV (27% vs 11%, p = 0.04); in the multivariate analysis MBL-low genotype (relative risk [RR] 7.3, p = 0.003), MASP2 variant (RR 6.4, p = 0.002), and acute GVHD II to IV (RR 3.8, p = 0.02) retained independent prognostic value. CONCLUSION: These results show for the first time that polymorphisms responsible for not only MBL but also MASP-2 deficiency are independent predictive factors for IFI after allo-SCT.

Acute Disease↗

PubMed2006

Follicular lymphoma in early stages: high risk of relapse and usefulness of the Follicular Lymphoma International Prognostic Index to predict the outcome of patients.

BACKGROUND AND OBJECTIVES: Patients with follicular lymphoma (FL) in advanced stages are currently deemed incurable with standard treatments. However, FL is considered to be eradicable in the small group of patients presenting with localized disease. The objective of this study was to analyze the clinical features and the outcome of a series of patients with FL in early stages with a long follow-up. PATIENTS AND METHODS: A total of 48 patients (25m/23f; median age: 50 yr) diagnosed consecutively with FL in Ann Arbor stage I (25 cases) or II (23) at a single institution with a median follow-up of 9.5 yr were included in the study. Main biological and clinical characteristics at diagnosis, including Follicular Lymphoma International Prognostic Index (FLIPI) were analyzed; treatment and response were assessed and analyzed for prognosis. RESULTS: The histologic subtypes were: FL type I, 20 cases (42%); type II, 24 (50%); type III, three (6%); and unclassifiable, one (2%). Distribution according to FLIPI was: low risk (36 cases) and intermediate risk (five cases). Treatment mainly consisted of combination chemotherapy (CHOP in 34 cases) plus involved-field radiotherapy in 26 cases. Forty patients (89%) achieved a complete response (CR), three (7%) a partial response, and two (4%) were non-responders; the remaining three patients did not receive therapy. No initial variable predicted CR achievement. About 57% of the patients in CR eventually relapsed with a relapse risk of 46% at 10 yr. Intermediate-risk FLIPI predicted failure-free survival. Histologic transformation was observed in six patients with a 10-yr risk of transformation of 13%. Twelve patients died during follow-up, in two cases as a result of unrelated causes. Overall survival (OS) at 10 yr was 79%. The FLIPI was the sole variable predicting OS. CONCLUSIONS: Although the majority of patients with localized FL achieve CR, the risk of relapse is high. The FLIPI is of prognostic value in these patients.

Adult↗

PubMed2006

New prognostic markers in CLL.

The individual prognosis of patients with chronic lymphocytic leukemia (CLL) is extremely variable. Although clinical stages remain the basis for assessing prognosis in CLL, a number of biological markers, particularly serum markers, cytogenetic abnormalities, IgVH mutations, CD38 and ZAP-70 expression in leukemic cells offer important, independent prognostic information. Before being incorporated into daily practice, however, these markers require standardization and validation in large, prospective trials. Meanwhile, treatment of patients with CLL not included in clinical studies should be decided on the basis of classical NCI/CLL Working Group criteria. An important area of research in CLL prognostication is the identification of markers useful for predicting response to therapy and its duration. Among them, del(17p), reflecting P53 abnormalities, is particularly important. Also relevant is del(11q), which points to ATM defects. There is also some correlation between IgVH mutational status, ZAP-70 and CD38 expression and response to therapy and its duration, although these relationships need further investigation. Finally, there is increasing evidence that response to therapy, particularly in those cases in which minimal residual disease is eradicated, is associated with longer survival.

Biomarkers↗

PubMed2006

Effect of NOD2/CARD15 variants in T-cell depleted allogeneic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Three single nucleotide polymorphisms (SNP) in the NOD2/CARD15 gene have been associated with the incidence and the severity of acute graft-versus-host disease (GVHD) following allogeneic stem cell transplantation (SCT). We hypothesized that the clinical effect of SNP in NOD2/CARD15 might be different in patients submitted to T-cell-depleted allogeneic SCT, in which donor T cells, the main effectors of GVHD, are eliminated. DESIGN AND METHODS: SNP 8, 12 and 13 in NOD2/CARD15 were studied using a Taqman protocol in 85 patients undergoing HLA-identical, T-cell-depleted SCT and in 71 of their sibling donors. RESULTS: NOD2/CARD15 variants were present in nine (11%) patients and six (8%) donors. The incidences of acute GVHD and chronic GVHD were not associated with either the donors' or recipients' NOD2/CARD15 variants. In contrast, these genetic variants were associated with a lower disease-free survival (17% vs. 48%, p=0.03). Death due to pulmonary infection was more frequent in the group of patients with NOD2/CARD15 variants. In the multivariate analysis, only NOD2/CARD15 variants (RR 2.3, p=0.04) and older age (RR 2.2; p=0.04) were independent prognostic factors for disease-free survival. INTERPRETATION AND CONCLUSIONS: NOD2/CARD15 variants have a deleterious effect on clinical outcome in T-cell-depleted allogeneic SCT, which is independent of GVHD. These results supports the hypothesis that the detrimental effect of NOD2/CARD15 variants in such a transplant setting might be produced by an alteration of the innate immune system more than by activation of the adaptive immune system.

Adult↗

PubMed2005

Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia.

Recently, considerable progress has been made in the identification of molecular and cellular markers that may predict the tendency for disease progression in patients with chronic lymphocytic leukemia (CLL) or detect minimal residual disease after therapy. These developments have created uncertainty for clinicians who hope to incorporate the use of these markers and new disease-assessment tools into standard clinical practice. However, clinical trials are required to determine whether poor-prognosis leukemia-cell markers, such as expression of unmutated immunoglobulin genes or the zeta-associated protein of 70 kDa (ZAP-70), can be used as the basis for determining the time or type of therapy. Pending the outcome of such trials, treatment decisions outside the context of a clinical trial still should be based on guidelines established by the most recent National Cancer Institute-sponsored Working Group.

Biomarkers, Tumor↗