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Summary: Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high‐risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV‐naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV‐exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL. [ABSTRACT FROM AUTHOR]

This study prospectively analysed the relationships between immunophenotypic and cytogenetic features of blast cells in 432 acute non-lymphoblastic leukemias (ANLL) at presentation. An abnormal karyotype was detected in 232 cases (54%). These abnormalities were related to immunophenotypic markers as detected using a consensual panel of monoclonal antibodies allowing lineage assignment and investigation of myeloid marker expression on blast cells. In univariate analysis, CD9, CD10, CD15, CD34 and TdT expression appeared significantly associated with chromosomal anomalies. Multivariate analysis identified CD34 and CD9 expression as independently predictive of the presence of at least one cytogenetic abnormality (P < 10(-4) and P < 0.03, respectively). Significant associations between immunophenotypic and karyotypic features were observed both within individual FAB subgroups and independently from morphological criteria. Specific features were seen in five ANLL entities: M0 or M1/B lineage antigen positivity/t(9;22) or del(11)(q23); M2/CD13-/t(8;21); M4/CD13+, CD34+, CD36+/inv(16); M4 or M5/lack of B lineage antigen/del(11)(q23) or t(9;11). More practically, and although the relationships demonstrated only represent a fraction of homogeneous immunophenotypic subgroups, identification of such immunophenotypic features should prompt careful karyotypic examination, eventually using molecular biology analysis on non-growing cells. [ABSTRACT FROM AUTHOR]

Evaluates data on the outcome of pregnancy following exposure to hydroxyurea. Description of the antineoplastic drug; Situations in which the data was collected; Observance of teratogenic effects after trimester exposures.

Multiple myeloma with IgG kappa monoclonal gammopathy and oliguric renal failure requiring hemodialysis was diagnosed in a 49-year-old man. Conventional therapy with VAD (vincristin, adriamycin, dexamethasone) failed to induce a complete response (CR) but this was subsequently obtained following two cycles of high-dose intravenous melphalan (70 mg/m2). A relapse occurred 8 months after CR which was treated by intensive myeloablative therapy combining total body irradiation (6 Gy over 2 days) and high-dose intravenous melphalan (140 mg/m2) followed by supportive PBSC transplantation. Hemodialysis was performed every other day during the myeloablative therapy and subsequent aplasia. Fluid subtraction allowed 1500 Cal/day intravenous alimentation and the only adverse event observed was a severe mucositis. A second CR was obtained which lasted 14 months. This observation indicates that multiple myeloma patients with end-stage renal failure can receive intensive myeloablative therapy without major toxicity. [ABSTRACT FROM AUTHOR]

Presents a case study of polyarteritis in a female patient 2 years after an allogeneic bone marrow transplant. Information on the clinical manifestations of chronic graft-versus-host disease (cGVHD); Similarities of cGVHD with polyarteritis nodosa (PAN); Differences of cGVHD with the manifestations of the classic PAN.

Presents the case study of a person diagnosed with minimally differentiated acute myeloid leukemia at relapse. Treatment given to the patient during the initial diagnosis of leukemia; Relapse of acute leukemia in the patient after ten months of completion of treatment; Diagnosis of B III acute lymphoid leukemia on relapse.

Purpose: Fifty percents of cancer arise in people older than 65-year-old. Most clinical trials in cancer treatment are limited in patients younger than 65-year-old. We review literature-describing particularity of cancer treatment in elderly patients., Current Knowledge and Key Points: Therapeutic decisions should be based on an estimation of the patient's life expectancy, and risks and benefits should be weighted up accordingly. Geriatric oncology is made of a geriatric evaluation of patient and of knowledge of clinical trial about elderly patients., Future Prospects and Projects: We present in this issue the principle of geriatric evaluation and the results of recent clinical trial on elderly cancer patients.

Haematological, immunophenotypic and cytogenetic characteristics were analysed in 241 patients with acute myeloid leukaemia (AML) M0, including 58 children. Children < 3 years and adults between 60 and 70 years of age were most frequently affected. Immunophenotyping showed a heterogeneous phenotype. Anti-myeloperoxidase was positive in about half of the patients. Cytogenetic data were available from 129 (54%) patients. A normal karyotype was found in only 24%. Most of the abnormalities were unbalanced and the chromosomes 5, 7, 8 and 11 were the most frequently affected. Survival data were available from 152 treated patients (63%). The median overall survival for all patients was 10 months, 20 months for children (n = 36), 10 months for the young adult group (n = 50) and 7 months for the elderly patients (n = 66) (P = 0.09). Karyotype was not a prognostic factor influencing survival. AML M0 shows the immunological characteristics of early progenitor cells, but the expression of the different markers and cytogenetic abnormalities is heterogeneous. The prognosis is poor compared with other de novo AML and similar to that of AML with multilineage dysplasia or AML following myelodysplastic syndromes.

Background and Objective: The first clinical studies of paclitaxel as a single agent for the treatment of relapsed or refractory low or intermediate grade non-Hodgkin's lymphomas (NHL) yielded controversial results regarding the response rates observed, mainly related to the dose and schedule of administration used. To obtain additional data concerning the efficacy and toxicity of paclitaxel in intermediate and high grade NHL we initiated a phase II study using a 3-hour infusion of high doses of paclitaxel., Design and Methods: The eligibility criteria included patients with relapsed or refractory aggressive NHL, a performance status < or = 2 (WHO index), a platelet count > or = 100,000/microL, a neutrophil count > or = 2,000/microL, measurable disease, and adequate hepatic function. Patients were excluded if they were infected with HIV, had a left ventricular ejection fraction < 50%, or prior peripheral neuropathy. Paclitaxel was administered as a 3-hour infusion at a dose of 250 mg/m2 every 3 weeks for a maximum of 6 courses., Results: Of 45 eligible patients, 42 received a total 73 courses of paclitaxel. Forty patients were assessable for response (89%), and 42 for toxicity (93%). Six patients (15%) achieved a partial (n = 4) or a complete remission (n = 2). Responses were observed in intermediate grade (n = 4) as well as in high grade lymphoma (n = 2). The main factor influencing the response to paclitaxel was the median duration of response to previous chemotherapy regimens which was 3 times longer in patients who responded to paclitaxel (16.3 months) than in patients who did not respond to paclitaxel (5.2 months) (p<0.05). The most common serious side effects were related to the hematologic toxicity of paclitaxel, and included grade IV granulocytopenia in 20 cases (48%), grade III/IV thrombocytopenia in 14 cases (33%) and grade III-IV anemia in 13 cases (31%)., Interpretation and Conclusions: Despite frequent manageable hematologic toxicity, paclitaxel is usually well tolerated at a dose of 250 mg/m2 given by a 3-hour infusion. However, the clinical efficiency as a single therapy seems modest in relapsed or refractory aggressive lymphoma.

We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819 acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4 undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of the French-American-British (FAB) subtype, one third of BAL, all four AUL, but only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified as: T-cell lineage (two thirds), mainly pro-T-ALL or T-I, and B lineage (one third); cells from 62% of these ALL cases coexpressed other myeloid markers (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML or ALL cases according to age being similar in the adult and pediatric groups. Our findings demonstrate that c-kit is a reliable and specific marker to detect leukemia cells committed to the myeloid lineage, and therefore should be included in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid commitment of the blasts. c-kit expression should score higher, at least one point, in the system currently applied to the diagnosis of BAL, as its myeloid specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c-kit identifies a subgroup of cases, which may correspond to leukemias either arising from early prothymocytes and/or early hematopoietic cells, both able to differentiate to the lymphoid and myeloid pathways.

The serum level of IL-6 was reported to reflect disease severity in patients with multiple myeloma. We used a specific radioimmunoassay to measure the level of IL-6 in 239 serum samples in which a monoclonal gammopathy was identified for the first time. The same sample was used for the measurement of serum C reactive protein and serum albumin. Then, an inventory of clinical and biological features allowed us to classify these patients into five groups: monoclonal gammopathy of undetermined significance (MGUS:128), multiple myeloma (MM:66), Waldenström's macroglobulinaemia (WM:27), non-Hodgkin's lymphoma (NHL:11) and chronic lymphocytic leukaemia (CLL:7). The number of patients with serum IL-6 (S-IL-6) level > 0.335 ng/ml (upper limit in normal sera) was significantly higher in the MM group (35%; Confidence Interval (CI) 23.5-46.5) compared with the MGUS group (15%; CI 8.8-21.2). The distribution of S-IL-6 levels was also significantly different between the groups (Mann-Whitney test: P < 0.01). High S-IL-6 levels were measured in 5/11 patients with NHL and 9/27 patients with WM. The distribution of S-IL-6 levels in these groups was the same as that in MGUS or MM groups. In patients with MM, elevated S-IL-6 levels were associated with haemoglobin level < 100 g/l (P < 0.005), bone marrow plasmocytosis > 50% (P < 0.005) and stages II and III in the Durie & Salmon staging system (P < 0.005). The S-IL-6 level was also related to light chain component excretion in urine (P < 0.01) and M component serum level for IgA (P < 0.01). In patients with MGUS, the S-IL-6 level correlated with serum CRP level (P < 0.05), serum lactate dehydrogenase (P < 0.05) and serum ferritin (P < 0.01). We conclude that the S-IL-6 level is a marker of high tumour burden in multiple myeloma. However, S-IL-6 level can be increased in patients with MGUS in relation to inflammatory parameters. Therefore the S-IL-6 level does not demonstrate high predictive value for the diagnosis of MM in patients with newly identified monoclonal gammopathy.

The immunophenotype of blast cells was investigated in a multicentric study of 154 adult acute myeloblastic leukemias (AMLs). A panel of 27 monoclonal antibodies (MoAbs) was tested in indirect immunofluorescence. Expression of CD14 (UCHM1), CD19 (SB4), CD36 (OKM5), and HLA-DR were associated with higher mean leucocyte counts. CD14 expression correlated with low hemoglobin level and the absence of CD33 (MY9) with low platelet counts. Extramedullary disease was associated with CD16 (Leu11b) and HLA-DR antigen positivity. The study of relationships between surface markers and FAB criteria confirmed the predominant expression of CD14 in the M5 sub-group (p less than 0.000001) and the association of CD19 and CD36 with monocytic M4/M5 subgroups (respectively p less than 0.00002 and p less than 0.000001). All patients received an induction therapy including an anthracycline and cytarabine. The median follow-up was 13 months. The achievement of complete remission (CR) was inversely correlated with CD34 (B13C5) and CD19 expression: CR was obtained in 31 of 59 (53%) CD34-positive AML versus 64 of 75 (85%) CD34-negative cases (p less than 0.0001) and 11 of 24 (46%) CD19-positive versus 95 of 122 (78%) CD19-negative cases (p less than 0.01). In univariate analysis, a longer survival was associated with CD33 expression and the combined phenotypes CD36+/CD19- and CD16+/CD14-. Conversely, the CD18(IOT18)+/CDw65(VIM2)- phenotype was related to shorter survival. The expression of CD19, of CD34, and of the combined phenotype CD14+/DR--correlated with shorter survival as demonstrated both in univariate and multivariate analysis (p less than 0.03 in each case in multivariate analysis).

Interleukin-6 (IL-6) was demonstrated to be a strong autocrine or paracrine plasmocytoma cell growth factor in humans. Using a bioassay, high serum IL-6 (S-IL-6) levels were correlated with disease severity in plasma cell dyscrasias. Since other cytokines could interfere with the bioassays, we developed a specific radioimmunoassay to study S-IL-6 levels in 102 patients with monoclonal gammopathy (MG). S-IL-6 level was studied by a double antibody radioimmunoassay using a rabbit polyclonal anti-IL-6 antibody and a human recombinant IL-6 as the standard. The lowest value of the standard significantly different from zero was found to be 78 pg/ml. Within-run and between-run precisions were characterized by a mean coefficient of variation of 3.72 and 5.5%, respectively. The mean analytical recovery was found to be 113% and the immunochemical identity of IL-6 standard and S-IL-6 was shown by dilution tests. IL-6 was detected in all tested sera. Sera from 66 healthy volunteers and 43 patients with acute leukemia or malignant lymphoma were tested as controls. In healthy subjects, S-IL-6 values were 294 +/- 86 pg/ml. MG were classified as multiple myeloma (MM), macroglobulinemia, and MG of undetermined significance (MGUS). The distribution of S-IL-6 levels in patients with MG was significantly higher than in healthy subjects but lower than in patients with acute leukemia or Hodgkin's lymphoma. Results obtained in 55 patients with MM were related to other biological parameters. S-IL-6 levels correlated with bone-marrow plasmacytosis (P less than .0005), serum-lactate dehydrogenase (S-LDH; P less than .005), serum beta 2 microglobulin (S -beta 2m; P less than .01), and serum calcium (S-Ca; P less than .025) and inversely correlated with haemoglobin (P less than .025). Our results indicate that 1) radioimmunoassay is suitable for the measurement of human IL-6 in serum; 2) high S-IL-6 levels are observed in a small number of patients with MG; and 3) S-IL-6 level correlates with tumour cell mass in patients with overt MM.