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Efficacy and safety of thalidomide in patients with acute myeloid leukemia.

Emerging data suggest an involvement of angiogenesis in the pathophysiology of acute myeloid leukemia (AML). Thus, antiangiogenic therapy could constitute a novel strategy for the treatment of AML. To test this hypothesis, a phase I/II dose-escalating trial was performed to study the safety and efficacy of thalidomide, a putative inhibitor of angiogenesis, in 20 patients with AML. Thirteen patients were assessable for both toxicity and response, tolerating a maximum dose of 200 to 400 mg daily for at least 1 month. Seven patients had to be prematurely withdrawn from drug administration owing to progressive disease and death (3 patients), personal decision (2 patients), or inability to tolerate thalidomide (2 patients). Overall, adverse events were fatigue, constipation, rash, and neuropathy (grade 1 to 2 in most patients). In 4 patients, a partial response, defined as reduction of at least 50% in the blast cell infiltration of the bone marrow accompanied by increases in platelet counts and hemoglobin values, was observed. One additional patient showed a hematologic improvement without fulfilling the criteria of a partial response. The responses lasted a median of 3 months (range, 1-8 months). In parallel, microvessel densities significantly decreased in these 5 patients during treatment with thalidomide (P <.05). This decrease was accompanied by declining plasma levels of basic fibroblast growth factor, one of the most potent angiogenic growth factors. In conclusion, single-agent thalidomide has antiangiogenic and antileukemic activity in AML, although a causal relationship between both effects has still to be proven.

Acute Disease↗

Elevated cerebrospinal fluid fibronectin concentration at diagnosis indicates poor prognosis in children with acute lymphoblastic leukemia.

We investigated whether the concentration of fibronectin (FN) in the cerebrospinal fluid (CSF) could be used for identifying patients with subclinical blast-cell infiltration in the central nervous system (CNS) and an increased risk of CNS relapse later in the course of their leukemia. Our series comprised 36 children with newly diagnosed acute lymphoblastic leukemia (ALL). The mean follow-up time was 54 months (range 5 to 96 months). The median concentration of CSF-FN at diagnosis was 2.24 mg/l (range 0.78 to 7.04 mg/l). The 3-year continuous complete remission rate for the 16 patients with CSF-FN concentrations less than or equal to 2 mg/l was 93% as compared with 37% for the 19 patients with CSF-FN greater than 2 mg/l (p = 0.001). When multivariate analysis was performed, the CSF-FN concentration retained its prognostic significance. When all relapses were considered as failures, the relative risks of relapse for patients with CSF-FN less than or equal to 2 mg/l and greater than 2 mg/l were I and 15.8 (95% confidence limits 1.8-135.6, p less than 0.02), respectively. If only CNS relapses (isolated and combined) were considered as failures, relative risks for the above-mentioned groups were I and 11.6 (1.4-99.5, p less than 0.05), respectively. We conclude that determination of the CSF-FN concentration may provide a new means of evaluating the CSF in children with ALL and may prove to be a sensitive indicator of leukemic CNS infiltration.

Adolescent↗

Prognostic predictors of squamous cell carcinoma of the buccal mucosa with negative surgical margins.

PURPOSE: To study the prognostic factors of squamous cell carcinoma of the buccal mucosa (BMSCC) with negative surgical margins. PATIENTS AND METHODS: Forty-five untreated negative marginal cases were studied for predictors of recurrence, cervical lymph node metastasis, and survival. Clinicopathologic features included age, gender, duration of tumor, primary tumor (T) classification, pathologic clinical stage, tumor differentiation, tumor thickness, number of mitoses, and lymphocytic infiltration. RESULTS: The recurrence and metastasis rate was 40% and 44.4%, respectively. With univariate analysis, the predictors of recurrence were T classification, tumor differentiation, pathologic clinical stage, and lymphocytic infiltration. Average tumor thickness was greater than 5.68 mm. For cervical lymph node metastasis, the predictors include T classification, tumor differentiation, and lymphocytic infiltration. Tumor thickness was greater than 5.17 mm; number of mitoses was greater than 2.92/high power field (HPF). With logistical regression, only tumor thickness was the predictor of recurrence. T classification and tumor thickness were the predictors for cervical lymph node metastasis. Using Cox multivariate proportional hazards regression model, the survival disadvantage factors were T classification and recurrence. The hazard grand for T classification was 2.185; for recurrence it was 74.808. CONCLUSIONS: Because T classification (between T1+T2 and T3+T4) and tumor thickness (more than 5.17 mm) were the predictors for cervical lymph node metastasis, neck dissection should be carried out routinely in T3 and T4 patients; whereas for T1 and T2 patients, neck dissection is necessary if tumor thickness is greater than 5.17 mm. T classification and recurrence are predictive factors for survival.

Aged↗

Blastic CD4 NK cell leukemia/lymphoma: a distinct clinical entity.

We report the findings of three new cases of a distinct clinicopathologic natural killer (NK) cell malignancy characterized by cutaneous, nodal and bone marrow infiltration by CD3-CD4+CD56+ NK blastic cells. Tumor cells were detected in bone marrow and in peripheral blood smears and showed finely distributed nuclear chromatin with nucleoli and a moderate amount of cytoplasm. Epstein-Barr virus (EBV) DNA was negative in the two tested cases. The immunophenotypes determined by flow cytometry were identical concerning mCD3-cytCD3-CD4+weakCD56+ HLA-DR+. The TCR was in germline configuration in the two cases tested. NK cell activity was demonstrated only in one out of the two cases tested. The negative reactions with alpha-naphthyl-acetate-esterase (ANAE), CD11b and CD14 strongly suggested that the tumor cells were not of the monocytic lineage.

Adolescent↗

Kidney involvement and renal manifestations in non-Hodgkin's lymphoma and lymphocytic leukemia: a retrospective study in 700 patients.

Renal involvement as part of systemic lymphoma (LY) is quite frequent, however, primary extranodal renal non-Hodgkin's lymphoma (NHL) is extremely rare, and only about 65 cases have been reported in the world literature. In a retrospective study of renal manifestations in 700 patients with documented LY and chronic lymphocytic leukemia (CLL) seen at our hospital during 1986-95, 83 patients had signs of acute renal failure. Only five of these had proven renal infiltration, but none of them satisfied the criteria for primary renal LY. Glomerulonephritis (GN) has also rarely been reported in association with LY and CLL, and only 37 glomerular lesions in NHL and 42 in CLL have been documented, respectively. GN may precede, coexist, or follow the diagnosis of LY by several years. Of the 42 cases of CLL reported worldwide, 36 had nephrotic syndrome. Renal failure was seen in about one third. The most common glomerular lesion reported is membranoproliferative GN, followed by membranous GN. In our study, we found only five biopsy-proven cases with GN amongst the 700 patients seen. In this report we also briefly describe some rare interesting associated renal syndromes in CLL and NHL.

Acute Kidney Injury↗

Anaplastic large cell malignant lymphoma with extensive eosinophilic or neutrophilic infiltration.

AIMS: We describe the clinicopathological features of eight cases of Ki-1 positive anaplastic large cell malignant lymphoma (Ki-1 ALCL) in which there was extensive infiltration by eosinophils and/or neutrophils in the absence of necrosis. METHODS AND RESULTS: The patients comprised four males and four females with an age range of 24-74 years. Five cases had originally been diagnosed as Hodgkin's disease and one as true histiocytic lymphoma. In all cases, there was massive infiltration by eosinophils and/or neutrophils sometimes to such an extent that malignant cells were obscured. Immunohistochemical staining was performed using the monoclonal antibodies CD30, CD15, CD45, CD20, CD3, CD45RO, epithelial membrane antigen (EMA), CAM5.2, vimentin and CD68. In all cases, tumour cells were strongly positive for CD30 but negative for CD15. One case was positive for CD45 but none expressed B or T-cell markers. Five cases were positive for vimentin and two for EMA. Three of seven patients in whom adequate clinical details were available had stage III or IV disease at presentation and four exhibited B symptoms. Four patients had a peripheral neutrophilia and one a peripheral eosinophilia. CONCLUSIONS: The study shows that an eosinophil and/or neutrophil-rich variant of Ki-1 ALCD exists, expanding the morphological spectrum of this tumour.

Adult↗

Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantation.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by a proliferation mainly of mature neutrophils. The prognosis is generally poor and an optimal therapeutic strategy remains to be determined. Allogeneic hematopoietic stem cell transplantation (HSCT) is expected to be the only curative therapy so far. We report a 46-year-old male with progressive CNL who underwent bone marrow transplantation from an HLA-matched unrelated donor. After engraftment was achieved on day 35, relapse of CNL was confirmed on day 50. The progression of CNL was very rapid afterward and infiltration to the central nervous system was observed. The Janus Kinase 2 (JAK2) V617F homozygous mutation was detected from the peripheral blood or bone marrow samples throughout the clinical course. From comparison with reports of successful HSCT for CNL in the literature, it was inferred that HSCT should be performed in a stable status before progression. Furthermore, JAK2 V617F-positive CNL may contain an aggressive disease entity in contrast to previous reports. Accumulation of experiences is required to establish a definite role of HSCT in the treatment of CNL and a prognostic significance of JAK2 mutation in CNL.

Antineoplastic Agents, Alkylating↗

Usefulness (or lack thereof) of immunophenotyping in atypical cutaneous T-cell infiltrates.

Our purpose was to evaluate the interobserver concordance for the diagnoses of mycosis fungoides (MF), atypical dermatoses (AD), and benign dermatoses (BD) and the impact of T-cell immunophenotyping on the diagnoses MF, AD, and BD. Specimens of MF (n = 57), AD (n = 27), BD and normal skin (n = 54) were reviewed by 2 hematopathologists and 1 dermatopathologist to establish diagnostic interobserver concordance by routine morphologic examination. Immunophenotyping was performed to evaluate expression of CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and MIB-1. The interobserver concordance was fair to moderate compared with the original diagnosis. Partial deletion of CD2 alone was associated significantly with MF. Epidermal deletions of 2 or 3 T-cell antigens or 2 T-cell antigens not including CD7 were associated significantly with MF. An elevated CD4/CD8 ratio correlated with MF. Morphologic features were most diagnostic of MF. Immunophenotyping generally resulted in downgrading of the reaction pattern but was helpful in distinguishing MF from benign dermatoses.

Adult↗

Intrathecal therapy of leptomeningeal CEM T-cell lymphoma in nude rats with anti-CD7 ricin toxin A chain immunotoxin.

We have established a new xenogeneic animal model of leptomeningeal metastasis (LM) by intracisternal inoculation of human CEM T-cell lymphoma into nude rats, and used it to evaluate the anti-lymphoma efficacy of an anti-CD7 ricin A chain immunotoxin (DA7). In vitro incubation with 2 microg/ml DA7 for 72 h inhibited CEM cells by 90% in a trypan blue exclusion assay. To establish its anti-lymphoma activity, one and four days after cisternal inoculation of 10(6) CEM cells, eight animals each were treated cisternally with 10 microg DA7 in 50 microl PBS or sham-treated with 50 microl PBS. Histopathologically, all eight sham-treated and five of eight DA7 treated animals showed typical features of LM with multilayers of tumor cells along the whole subarachnoid space and the ventricular walls, as well as subependymal and diffuse parenchymal tumor cell infiltration. Three DA7 treated animals were free of tumor. Two of these animals were asymptomatic long-term survivors (> 90 days). The third tumor-free animal suddenly died on day 51. Histology revealed viral myocarditis. Median symptom-free survival was 51 days (range 29-90+ days) in DA7 treated and 34 days (range 29-87 days) in sham-treated animals (p = 0.12, log-rank test). Histologically, no signs of neurotoxicity or systemic toxicity was found. However, DA7 treated animals showed a tendency to a slower weight increase on days 6-28 after tumor cell inoculation. Our results indicate that this model is useful in studying leptomeningeal seeding and intracisternal treatment of lymphoma. The demonstrated anti-tumor effect of DA7 treatment deserves further evaluation especially regarding the application of DA7 in early stages of LM from T-cell lymphoma.

Animals↗

L and E selectins in acute myeloid leukemia: expression, clinical relevance and relation to patient outcome.

UNLABELLED: The aim of this study was to assess circulating soluble L (sL) and soluble E (sE) selectins adhesion molecules in acute myeloid leukemia (AML) blasts in order to evaluate their clinical significance. Fifty patients with AML (4 M0, 8 M1, 16 M2, 5 M3, 7 M4, 6 M5, 4 M6) were included in this study. sL and sE selectins were evaluated at diagnosis, remission and in relapsed patients; whole membrane expression of L and E selectins by AML blast was investigated only at diagnosis. In addition, 15 normal persons were studied as a control group. sL and sE selectins were significantly higher in AML patients at diagnosis when compared to controls (P<0.01), but less at remission (P<0.01). Furthermore, elevated sL and sE selectin levels were detected in patients with AML at relapse. sE and sL selectins were significantly higher in AML patients with extramedullary infiltration as compared to patients without extramedullary disease (P<0.001). Membrane expression of L selectin was positive in 20% of AML patients. However, none of the patients showed significant E selectin expression. Patients with higher sE and sL selectins at diagnosis have high probability of relapse compared to those with normal levels (P<0.01 and <0.001, respectively). The overall relapse predictability of sE and sL selectins was 84%. Moreover, patients with higher sE and sL selectins levels had shorter event free survival than patients with lower levels (P<0.001 for both). The overall mortality prediction using sE, sL, and cellular L selectin was 96%. IN CONCLUSION: (1) AML blast cell express and release sL selectins but not sE selectin, (2) sE and sL selectins and cellular L selectin may be useful prognostic markers in evaluating AML patients at diagnosis.

Acute Disease↗

Tetrasomy 8 in acute monoblastic leukemia (AML-M5a) with myelosarcomatosis of the skin.

We report a new case with isolated tetrasomy 8, an 82-year-old female patient in whom multiple disseminated nodular skin infiltrations up to 5 cm in diameter preceded acute monoblastic leukemia (AML-M5a). Despite an initial response to chemotherapy and radiotherapy, the patient died 1 year after diagnosis of relapsed leukemia. To assess the size of the tetrasomic clone, fluorescence in situ hybridization (FISH) analysis with a centromere-specific chromosome 8 probe was performed. Seventy percent of interphase cells showed four signals and 22% showed three signals. Because this trisomic clone was not detected by conventional cytogenetics, tetrasomic cells may have a proliferation advantage in vitro. Whether tetrasomy 8 arises from a simultaneous mitotic nondisjunction of both chromosomes 8 during one cell division or evolves secondarily from trisomy 8 through a second mitotic error is not known. Alternatively, trisomy 8 may originate from tetrasomy 8 by loss of one chromosome 8.

Aged↗

Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol.

Patient-tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 10(5) cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m(2) per day for 5 days every 4 weeks for 6 cycles, followed by consolidative high-dose cyclophosphamide (1.5, 2.25, or 3g/m(2)). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were cPCR positive. In contrast, flow cytometry for CD5-CD19 dual staining and kappa--lambda clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were cPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry. (Blood. 2001;97:1929-1936)

Antigens, CD↗

Assessment of proliferative activity in leukaemic bone marrow using the monoclonal antibody Ki-67.

AIMS: To investigate proliferative activity in leukaemic and lymphomatous bone marrow infiltrates and to assess the feasibility of transport of specimens among institutions. METHODS: Proliferative activity in bone marrow trephine cryosections from 99 patients with non-Hodgkin's lymphoma (NHL), 23 patients with acute myeloid leukaemia (AML), 11 with acute lymphoblastic leukaemia (ALL), and two with acute undifferentiated leukaemia (AUL) was investigated. Infiltration was seen in 52 out of 99 cases of NHL on bone marrow cryosections. A score was devised to assess pathological infiltrates in bone marrow trephine cryosections using the monoclonal antibody Ki-67. This method of scoring gave a measure of non-erythroid proliferative activity. RESULTS: Mean Ki-67 positivity in bone marrow infiltrates in 31 low grade B cell lymphomas (Kiel classification) was 0.3% before and 4.7% after treatment, 16.4% in seven high grade B cell lymphomas, and 17.8% in 12 peripheral T cell lymphomas. In 48 cases of NHL, bone marrow cryosections had not been infiltrated, and in all but one case the percentage of Ki-67 positive cells in normal marrow was less than 3%; the remaining case showed coexistent myelodysplasia and 8% bone marrow Ki-67 positivity. In eight cases of common ALL at diagnosis, the mean Ki-67 positivity in marrow cryosections was 24.9%, significantly higher than the 2.4% Ki-67 positivity seen in AML (p < 0.05). One of the two cases of common ALL with less than 1% Ki-67 positivity was refractory to treatment. CONCLUSIONS: Proliferative activity of erythroid elements in the bone marrow varies greatly. Immunostaining of bone marrow cryosections using Ki-67 permits accurate assessment of non-erythroid proliferative activity in lymphomas and leukaemia. High grade B cell lymphomas and peripheral T cell lymphomas invading the marrow have very similar mean proliferative activities. Such levels of proliferation are of the same order as those seen in common ALL, but much higher than those seen in AML.

Adult↗

Assessment of T-cell clonality via T-cell receptor-gamma rearrangements in cutaneous T-cell-dominant infiltrates using polymerase chain reaction and single-stranded DNA conformational polymorphism assay.

Discerning the pathologic significance of cutaneous T-cell infiltrates can pose a diagnostic challenge for dermatopathologists. Reactive conditions such as drug-associated lymphomatoid hypersensitivity and lymphomatoid lupus erythematosus can demonstrate lymphoid atypia and a phenotype resembling cutaneous T-cell lymphoma (CTCL). Further, lymphoid dyscrasias such as pityriasis lichenoides chronica, large plaque parapsoriasis, and atypical pigmentary purpura confuse the picture because they not only mimic CTCL but also represent prelymphomatous states with inherent malignant potential. Although the emergence of a dominant clone has been considered a clue indicative of a T-cell dyscrasia, there are reports concerning the identification of monoclonality in biopsies of reactive lymphoid infiltrates. We have conducted a modified single-stranded DNA conformational polymorphism (SSCP) assay using paraffin-embedded, formalin-fixed tissue on 92 T-cell-rich biopsies to determine the relative specificity and sensitivity of this methodology. In addition, laser capture microdissection (LCM) was performed on 22 of the 92 samples to isolate the area of interest and to compare its specificity and sensitivity with those SSCP assays performed without LCM. We found that monoclonality or oligoclonality is 86% specific for preneoplastic and neoplastic states, whereas the finding of polyclonality appears to be relatively specific for a reactive process. Some cases of reversible T-cell dyscrasia produced a molecular profile mimicking lymphoma or prelymphomatous states by virtue of monoclonality or oligoclonality. Although LCM appears to improve the sensitivity for detecting preneoplastic conditions, the relative specificity appears to be the same as that encountered with routine SSCP.

Clone Cells↗

Cleaved L-selectin concentrations in meningeal leukaemia.

Involvement of the central nervous system has important therapeutic implications in acute leukaemia. Because the identification of blast cells in cerebrospinal fluid (CSF) is often difficult, there is a need for sensitive markers of leukaemic infiltration. Since the shed form of L-selectin (sL-selectin) is frequently increased in acute leukaemia (sL-selectin+ leukaemia), we examined whether assay of sL-selectin in CSF could improve our ability to detect such meningeal involvement. CSF sL-selectin was significantly (p < 0.001) higher in 15 patients with sL-selectin+ meningeal leukaemia (median 60 ng/mL, range 34-150) than in 20 patients with acute leukaemia without meningeal involvement (12 ng/mL, 1-39) or 88 control patients (14 ng/mL, 0-37). Serial measurements of sL-selectin in patients with sL-selectin+ leukaemic meningitis showed increased CSF concentrations of the cleaved receptor in 4 patients with therapy-resistant meningeal leukaemia and sustained normal concentrations in 9 patients in remission. Our results suggest that CSF sL-selectin may be a useful marker in the detection of meningeal involvement by blast cells in patients with sL-selectin+ leukaemia.

Adult↗

Retinal vasculitis caused by adult T-cell leukemia/lymphoma.

BACKGROUND: To report a case of lymphomatous infiltration and bilateral retinal vasculitis observed among 83 cases of adult T-cell leukemia (ATL) treated in the University Hospital Center in Fort-de-France (Martinique, French West Indies) between 1984 and 2003. CASE: A complete clinical ophthalmologic examination was performed in this patient along with fluorescein angiography. OBSERVATIONS: After being checked for diffuse adenopathies, myodesopsias, and phosphenes, the 35-year-old patient was diagnosed with ATL. The ocular impairment, present since the onset of ATL as peripheral subretinal infiltrates, spread progressively and afferently to the rest of the retina in the form of an essentially venous vasculitis. Impairment of the vitreous was noted only in the end stages of disease progression. As ocular lesions progressed, the general state of the patient degraded at the same time despite chemotherapeutic measures. CONCLUSION: Among the more than 300 seropositive for human T-cell lymphotropic virus type 1 (HTLV-1) or patients with HTLV-1-associated myelopathy/tropical spastic paraparesis treated at our hospital in the last 20 years, and among the 83 cases of ATL, only this single case of retinal vasculitis associated with HTLV-1 was observed (1/83, 1.2%) in Martinique, confirming the geographic variability of the clinical phenotype of HTLV-1 infection. The incidence of retinal vasculitis in ATL patients may signify an even worse prognosis than initially indicated.

Adult↗

Immunophenotyping of acute lymphoblastic leukaemia in routinely processed bone marrow biopsy specimens.

AIMS: To assess the value of immunophenotyping of acute lymphoblastic leukaemia (ALL) in routinely processed bone marrow trephine biopsy specimens and to establish a minimum panel of antibodies to assess lymphoid lineage and enable differentiation from acute myeloid leukaemia. METHODS: 45 routinely processed bone marrow biopsy specimens (formalin fixed, paraffin embedded and mildly decalcified in EDTA) reported to contain leukaemic infiltrates on the basis of cytomorphological and enzyme-cytochemical analysis of bone marrow smears (22 c-ALL, 11 T-ALL, 2 B-ALL, 10 u-ALL (unclassified)) were immunostained by the ABC method with a broad panel of 26 antibodies against various haemopoietic antigens. RESULTS: Staining with antibodies directed against myeloperoxidase and lysozyme showed that seven cases were either biphenotypic or mixed leukaemias (2), or of myelogenous origin (acute myeloid leukaemia (AML)-M1 (2); AML-M4 (2); AML-M5a (1)). Five of these seven cases had been diagnosed initially as u-ALL. Three further cases with no compact leukaemic infiltrates were excluded. ALL was confirmed in the remaining 35 cases. Because of revised diagnoses, the total numbers of ALL subtypes changed (23 c-ALL, 8 T-ALL, 2 B-ALL, 2 u-ALL). Immunostaining of more than 10% of blast cells in at least one case was found with 19 of the 26 antibodies. The most sensitive lineage specific antibodies for diagnosis were found to be anti-CD10 for c-ALL (22/23) and beta F1 for T-ALL (6/8). Expression of aberrant antigens was fairly common--for example, 7/23 cases of c-ALL stained with antibodies against T cell associated antigens. CONCLUSIONS: Immunohistochemical investigation of routinely processed bone marrow biopsy specimens enables reliable detection of ALL subtypes c-ALL and T-ALL. A minimum panel of antibodies, against TdT, CD34, myeloperoxidase, lysozyme, CD10, CD79a, and CD20, and the antibody beta F1, is proposed for the immunophenotyping of acute leukaemia.

Antigens, Neoplasm↗

De novo acute B cell leukemia/lymphoma with t(14;18).

The t(14;18)(q32;q21) translocation is the most common translocation in B cell malignancies being found in 80% of follicular lymphomas and about 20% of diffuse large B cell lymphomas. Only rare cases of de novo acute B cell lymphoblastic leukemia with t(14;18) have been described. We describe five cases of this entity which appears to have very homogeneous clinical, phenotypic and genotypic features. None of these patients had prior history of follicular lymphoma. The disease was characterized by acute clinical features with nodal and/or extranodal disease, massive bone marrow infiltration and rapid increase of circulating blast cells of mature B cell phenotype. All patients disclosed complex chromosomal and molecular abnormalities involving at least the BCL-2 and c-MYC genes. Furthermore, three patients had evidence of BCL-6 involvement and one patient had a p53 mutation. Despite intensive chemotherapy, including for two patients allogeneic bone marrow transplantation in first complete remission, all patients died within a few months. Neuro-meningeal relapse occurred in three of the five patients in spite of neuro-meningeal prophylaxis. De novo leukemia/lymphoma with t(14;18) is a rare entity with a very poor prognosis. Whether early bone marrow transplant could modify the natural history of the disease remains to be determined. An intensive neuro-meningeal prophylaxis appears to be mandatory in these patients.

Adult↗