Evaluation of minimal residual disease using reverse-transcription polymerase chain reaction in t(8;21) acute myeloid leukemia: a multicenter study of 51 patients.

PURPOSE: Most studies using various reverse-transcription polymerase chain reaction (RT-PCR) techniques reported that the detection of the AML1-ETO fusion transcript was a common finding in long-term complete remission (CR) in acute myeloid leukemia (AML) with t(8;21) translocation. However, larger prospective studies with interlaboratory quality control may be important to investigate more precisely the clinical usefulness of studying minimal residual disease with RT-PCR in t(8;21) AML. PATIENTS AND METHODS: We collected 223 marrow samples from 51 patients with t(8;21) AML diagnosed in five centers and tested all samples by two different RT-PCR techniques (a nested technique and a one-step technique, with a sensitivity of 10(-6) and 10(-5), respectively) in two different laboratories. RESULTS: Samples from 14 patients in long persistent CR (median follow-up duration, 112 months) were taken at least twice, and all were PCR-negative by both techniques. Samples were prospectively taken from 37 patients after achievement of first CR and/or second CR, before intensive consolidation treatment, and every 3 to 6 months after completion of therapy. Patients who converted to PCR negativity with the one-step technique (60%) or both techniques (48%) after CR achievement had a longer CR duration than those with persistently positive PCR results (two-sided log-rank test, P =.0001). Patients who became PCR-negative with the one-step technique before intensive consolidation (23%) had a lower relapse rate (11% v 72%) and a longer CR duration than those who remained persistently PCR-positive at that point (two-sided log-rank test, P =.0015). CONCLUSION: Patients with AML with t(8;21) in long-term remission were all PCR-negative. In prospectively studied patients, a good correlation was found between negative PCR results and absence of relapse. Early negative results with the one-step RT-PCR technique, before consolidation treatment, seemed to carry an especially good prognosis, suggesting that RT-PCR analysis could help in choosing the type of consolidation therapy in patients with t(8;21) AML.

Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b. PATIENTS AND METHODS: Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms. RESULTS: Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months). CONCLUSION: Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.

Stromal factors support the expansion of the whole hemopoietic spectrum from bone marrow CD34+DR- cells and of some hemopoietic subsets from CD34+ and CD34+DR+ cells.

Ex vivo expanded bone marrow CD34+DR- cells could offer a graft devoid of malignant cells able to promptly reconstitute hemopoiesis after transplant. We investigated the specific expansion requirements of this subpopulation compared to the more mature CD34+ and CD34+DR+ populations. The role of stromal factors was assessed by comparing the expansion obtained when the cells were cultured in (1) long-term bone marrow culture (LTBMC) medium conditioned by an irradiated human BM stroma (CM), (2) medium supplemented with 15% FBS (FBSM) and (3) non-conditioned LTBMC medium (LTM) for 21 days. The effect of the addition of G-CSF (G) and/or of MIP-1alpha (M) to a combination of IL-3, SCF, IL-6 and IL-11 (3, S, 6, 11) was analyzed. Compared to CD34+DR- cells, CD34+ and CD34+DR+ cells gave rise to a similar number of viable cells and to a lower progenitor expansion. The expansion potential of CD34+ and CD34+DR+ cells was equivalent in CM and in FBSM except for both the emergence of CD61 + megakaryocytic cells and LTC-IC maintenance which were improved by culture in CM. In contrast, expansion from CD34+DR- cells was enhanced by CM for all the parameters tested. Compared to FBSM, CM induced a higher level of CFU-GM and BFU-E expansion and allowed the emergence of CD61+ cells. HPP-CFC were maintained or expanded in CM but decreased in FBSM. Compared to input, the number of LTC-IC remaining after 21 days of CD34+DR- expansion culture was strongly decreased in FBSM and variably maintained or expanded in CM. Comparison with LTM indicated that stroma conditioning is responsible for this effect. G-CSF significantly improved CFU-GM and HPP-CFC expansion from CD34+DR- cells without being detrimental to the LTC-IC pool. The growth of CD61+ cells was significantly enhanced by G-CSF in CM. Addition of MIP-1alpha had no significant effect either on progenitor expansion or on LTC-IC, regardless of culture medium. We conclude that factors present in stroma- conditioned medium are necessary to support the expansion of the whole spectrum of hematopoietic cells from CD34+DR- cells and to support the expansion of cell subsets from CD34+ and CD34+DR+.

Phase I/II study of 2-chloro-2'-deoxyadenosine with cyclophosphamide in patients with pretreated B cell chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma.

Because of their substantial in vitro synergy, we conducted a dose-escalation study of cyclophosphamide (CP) added to 2-chloro-2'-deoxyadenosine (CdA) in patients with previously treated chronic lymphocytic leukemia and non-Hodgkin's lymphoma. CdA was given at a fixed dose (5.6 mg/m2/day) as a 2-h intravenous (i.v.) infusion, immediately followed by a 1-h i.v. infusion of CP, for 3 days. The initial daily CP dose was 200 mg/m2, and was escalated by 100 mg/m2 increments in successive cohorts of three to six patients to determine the maximum-tolerated dose (MTD). Additional patients were included at the MTD to extend toxicity and response analysis. Twenty-six patients received 68 cycles of chemotherapy. The MTD of CP after CdA 5.6 mg/m2, was 300 mg/m2. Acute neutropenia was the dose-limiting toxicity of this regimen, which was otherwise well tolerated. Delivery of repeated cycles was not feasible in eight patients (31%) because of prolonged thrombocytopenia. Severe infections were seen in three of 68 cycles (4%). The overall response rate was 58% (15 of 26; 95% CI, 36-76%), with 15% complete responses and 42% partial responses. These data show the feasibility of the association of CdA with CP. Given the response rate observed, further studies of this regimen are warranted in untreated patients, in particular with chronic lymphocytic leukemia and with Waldenström macroglobulinemia.

Allogeneic bone marrow transplantation for AL amyloidosis.

AL amyloidosis is an infiltrative disorder characterized by the extracellular deposition of insoluble fibrillar immunoglobulin light chains whose production results from a plasma cell dyscrasia. Treatment with melphalan has resulted in an improvement in a few patients. Recently, intensive chemotherapy followed by autologous or syngeneic stem cell support has been shown to offer potential benefit. Allogeneic stem cell support after intensive therapy would retain the benefits of autologous transplantation, with the additional advantages of a tumor-free graft and of a possible graft-versus-tumor effect. We report a patient with AL amyloidosis and significant proteinuria. She improved after an allogeneic bone marrow transplantation.

Prophylaxis of graft-versus-host disease in identical sibling donor bone marrow transplant by anti-IL-2 receptor monoclonal antibody LO-Tact-1.

The efficacy of the rat monoclonal IgG2b antibody LO-Tact-1 specific for the human interleukin-2 (IL-2) receptor was evaluated for prophylaxis of graft-versus-host disease (GVHD) in patients who received transplants of marrow from HLA-matched sibling donors. Fifteen patients received cyclosporine (CsA) + antibody LO-Tact-1, 0.2 mg/kg/day from day +7 to day +28. Twelve additional patients were administered methotrexate (MTX) + CsA+antibody LO-Tact-1, 0.4 mg/kg/day from day -1 to day +28. The antibody was well tolerated. Engraftment was not affected. GVHD grade > or = II occurred in six of 15 and eight of 12 patients receiving CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (P = 0.52). GVHD grade > or = II developed in patients at a median of 32 and 34 days with CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (log-rank test, P = 0.57). GVHD contributed to death in four patients who were administered CsA+LO-Tact-1 and in one patient who was administered MTX+CsA+LO-Tact-1. Chronic GVHD occurred in two patients who were treated with CsA+LO-Tact-1 and in two patients treated with MTX+CsA+LO-Tact-1. Throughout therapy, serum levels of LO-Tact-1 ranged from 2 to 10 mg/l. There was no correlation between serum levels of LO-Tact-1 and the occurrence of GVHD. GVHD occurred in 10 patients during LO-Tact-1 prophylaxis. There was no significant difference between relapse or survival rates among the patient groups. We conclude that, while free of adverse effects, monoclonal anti-IL-2 receptor antibody LO-Tact-1 does not improve prophylaxis of GVHD in HLA-matched sibling BMT.

Long-term culture of autologous transplanted bone marrow for acute myeloid leukaemia: evidence for an in vitro haemopoietic defect and lack of correlation with the speed of engraftment.

Haematological recovery after autologous bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) is often delayed and available laboratory assays cannot accurately predict speed of engraftment. By using the long-term bone marrow culture (LTBMC) method, we attempted to define the haemopoietic defect underlying this slow engraftment, and assessed the usefulness of LTBMC in predicting engraftment. Cryopreserved bone marrow (BM) harvested from three different groups (AML autografts, n = 18; autografts for non-leukaemic diseases, n = 23; normal donors. n = 10) were cultured and their growth was compared and correlated with the speed of engraftment. In the AML autografts, non-adherent and adherent progenitor production was significantly reduced compared with normal BM during the whole culture period (P < 0.01). None of the LTBMC parameters was found to correlate with engraftment after autologous BMT. The non-leukaemic autografts showed progenitor production intermediate between normal and AML autografts. Their progenitor content at the end of the culture period (reflecting the stem cell pool) was not statistically different from normal BM. In this group, most of the progenitor cell contents, during LTBMC correlated with neutrophil (rs = -0.618 to -0.879, P < 0.01) and platelet (rs = -0.479 to -0.707, P < 0.02) recovery. The conclusion drawn from these results is that AML autografts are defective in their ability to sustain in vitro haemopoiesis, but this in vivo defect does not correlate with the slow haemopoietic recovery after autologous BMT. In contrast, LTBMC of autografts for non-leukaemic diseases, whose defect affects the stem cell pool to a lesser extent than BM in AML correlates with the speed of engraftment.

Karyotype in acute myeloblastic leukemia: prognostic significance in a prospective study assessing bone marrow transplantation in first remission.

To evaluate the prognostic value of the karyotype in acute myeloblastic leukemia when patients are allocated to have either autologous bone marrow transplantation (BMT) or allogeneic BMT at the time of first remission (CR1), we have prospectively followed 134 consecutive patients from diagnosis. CR was achieved in 118 patients. Allogeneic BMT and autologous BMT were performed in 25 and 43 CR1 patients, respectively. Applying the karyotype classification of Keating et al for remission duration (favorable: t(15;17), inv(16); intermediate: normal, X -Y, t(8;21); unfavorable: other abnormalities), 10 patients had a favorable, 49 an intermediate, and 44 an unfavorable karyotype. The 5-year leukemia-free survival (LFS) probabilities for patients with a good, intermediate and unfavorable karyotype were 65%, 32% and 11%, respectively (log rank test P = 0.0019). The probabilities of relapse were 35% in patients with a favorable karyotype, 52% with an intermediate karyotype and 87% with an unfavorable karyotype (P = 0.0004). In the patients who had autologous BMT in CR1, the LFSs were 100%, 33% and 10% with favorable, intermediate and unfavorable karyotype, respectively (P = 0.04). The karyotype was of no prognostic value in patients receiving allogeneic BMT who had BMT in CR1. This study shows that the karyotype retains its prognostic value when the intentions is to treat patients with acute myeloblastic leukemia in CR1 with BMT. Autologous BMT was not able to improve the poor prognosis associated with an unfavorable karyotype.

Chronic myeloid leukemia with a rare variant Philadelphia translocation: t(9;22;21)(q34;q11;q22).

A case of chronic myeloid leukemia displaying an uncommon t(21;22)(q22;q11) is reported. For the first time, this translocation has been characterized by fluorescence in situ hybridization (FISH) and the reverse transcriptase polymerase chain reaction (RT-PCR). FISH, with the use of whole-chromosome painting probes and probes specific for the BCR and ABL genes, showed a three-way variant Philadelphia translocation (9;22;21)(q34;q11;q22) with a BCR/ABL fusion residing on the der(22). In addition, RT-PCR demonstrated a b2a3 BCR/ABL fusion transcript. Underlying mechanisms and prognostic implications are discussed.

Treatment of acute lymphoblastic leukemia in the elderly: an evaluation of interferon alpha given as a single agent after complete remission.

Although interferon (IFN) has been used in elderly patients with acute lymphoblastic leukemia (ALL), the benefits from IFN therapy have not been properly assessed, especially as it was given combined with other cytotoxic drugs, which obscured the role of IFN if any. In 1997, we started a study aimed at improving our previous results in elderly patients with ALL and at assessing the therapeutic role of IFN in this disease. Fifty-eight patients with ALL, aged 55-81 years (median: 64.9 years), were randomly allocated to treatment with vindesine or vincristine during induction. After a first consolidation course, IFN was administered as a single agent for three months together with cranial radiotherapy. Chemotherapy was then resumed with a second consolidation course and maintenance. A complete remission (CR) was obtained in 58% of patients (CI: 45-71%), significantly less than in our previous study which included IFN combined with chemotherapy during maintenance (CR: 85%, CI:70-94%, p = 0.007). Overall survival (median: 289 vs 434 days in the previous study, p = 0.01) and disease-free survival (median: 146 vs 427 days, p = 0.009) were also inferior in the present study. In particular, the pattern of relapses over time suggested that the 3 month IFN treatment phase with no additional chemotherapy might have contributed to the comparatively poor outcome of this cohort. In addition, vindesine given during induction did not prove less neurotoxic than vincristine, did not improve the CR rate, and had no impact on survival. In conclusion, although similar to published studies in elderly patients with ALL, this study is inferior to our previous one. INF, given as a single drug, has a modest role if any in the treatment of older persons with ALL.

Impact of uncontrolled freezing and long-term storage of peripheral blood stem cells at - 80 °C on haematopoietic recovery after autologous transplantation. Report from two centres.

Controlled-rate freezing and storage in vapour phase nitrogen are used by most transplantation teams for the cryopreservation and storage of peripheral blood haematopoietic stem cells (PBSC). In this study, we analysed 666 autologous PBSC transplants after uncontrolled freezing and storage of PBSC at -80 °C. Statistical analysis showed that neutrophil recovery was associated with both the infused CD34(+) cell dose (P=0.01) and the post transplantation use of growth factors (P<0.001) and that platelet recovery was associated with the infused CD34(+) cell dose (P<0.001) and with the diagnosis (P=0.02). We analysed three groups according to the duration of the cryopreservation period (less than 6 months, between 6 and 12 months or more than 1 year). Haematopoietic recovery was not found to be adversely affected by longer storage at -80 °C. The haematopoietic recoveries of 50 pairs of sequential transplantations from the same PBSC mobilization were analysed. Despite prolonged cryopreservation, there were no statistically significant differences in neutrophil (P=0.09) or platelet (P=0.22) recovery in the second compared with the first transplant. In conclusion, the long-term storage of PBSC at -80 °C after uncontrolled-rate freezing is an easy and comparatively inexpensive cryopreservation method that leads to successful haematopoietic recovery even after prolonged storage.

Pericarditis induced by high-dose cytosine arabinoside chemotherapy.

Pericarditis is a rare side effect of chemotherapy. We report here the case of a patient treated with high-dose cytosine arabinoside (HD ara-c) who developed severe pericarditis. Interruption of HD ara-c and initiation of corticosteroid treatment were effective in resolving the pericardial effusion. This case illustrates this rare but potentially life-threatening cardiac complication of HD ara-c therapy as well as the beneficial effect of corticosteroid treatment.

[Hypereosinophilia syndrome. Apropos of 2 cases and literature review]. / Le syndrome hypereosinophilique (SHE). A propos de deux cas et revue de la littérature.

Idiopathic hypereosinophilic syndrome is characterized by prolonged eosinophilia of undetected cause and multiple organ system involvement (lung, kidney, nervous system, skin,...). Nevertheless, the prognosis has been correlated with heart involvement, which usually results in a restrictive cardiomyopathy with apical obliteration by fibrosis, mural thrombi and mitral and tricuspid regurgitation. This disease has a wide range of severity: some patients suffer from a real myeloproliferative syndrome and may develop blastic transformation while others present only skin involvement or are asymptomatic. Corticosteroids and hydroxyurea are both effective treatments. Interferon alpha seems to be active for the myeloproliferative form of the disease. Cytotoxic activity of activated eosinophil granular proteins may play an important role in tissue damage. The cause of eosinophilic proliferation (primitive malignant proliferation or resulting from a T lymphocyte stimulus) and activation remains uncertain.

Penicillin or vancomycin plus ceftazidime in febrile neutropenic patients after stem cell transplantation.

The response of gram-positive cocci to third generation cephalosporin therapy in febrile neutropenic patients is not optimal. We evaluated the safety and efficacy of ceftazidime plus penicillin (C + P) and compared it to ceftazidime plus vancomycin (C + V) in febrile neutropenic patients. The study includes 64 patients admitted to the Department of Haematology. Thirty-six patients were treated with C + V and 28 patients with C + P. Control of infection was observed in 78% of the patients in the C + V group and in 57% of the patients in C + P group (p = 0.5). Infection was the cause of the death of 1 patient in each group. We conclude that the combination of C + P has the same activity as the combination of C + V in febrile neutropenic patients. The morbidity and mortality were identical in both groups but cost effectiveness was in favour of the C + P group.

Evolution of bone marrow fibrosis and stromal antigenic expression in chronic myeloid leukemia on alpha interferon and Ara-C therapy.

We conducted a retrospective study to assess the changes in bone marrow (BM) stromal antigenic profile and fibrosis in chronic myeloid leukemia (CML) under combined interferon-alpha (IFN) and Ara-c therapy. Bone marrow biopsies were taken before therapy and twice (at 4 and 15 months) during therapy in 10 CML patients and compared with non-CML samples. Collagen and reticulin fibrosis was assessed by histochemical methods and phenotypic changes were studied by immunohistochemistry (APAAP) with antibodies directed against endothelial cell antigens, cell adhesion molecules, and HLA-DR. It was found that: (1) BM endothelial cells in patient and in control specimens showed a specific pattern of antigen expression: high expression of FVIII and CD34 (except on sinusoids for the latter), variable expression of UEA I, and no expression of HLA-DR and E-selectin. (2) Compared to non-CML controls, CML specimens at diagnosis showed an increased reticulin fibrosis and a decreased expression of CD61 on megakaryocytes and of CD31 on vessels and hemopoietic cells. (3) Treatment did not influence BM fibrosis, the vascular content of the BM, or the expression of the antigens tested except an increase in the number of CD34+ sinusoids (5/10 patients), an increase in the number of HLA-DR+, and a decrease in the number of CD34+ hemopoietic cells (6/10). (4) On therapy, difficulty in aspiration and/or reduced BM fragment numbers were noted in 8 of 10 patients whose bone marrow was still normocellular or slightly hypercellular. In conclusion, CML samples at diagnosis showed increased fibrosis and decreased CD31 and CD61 expression compared to controls. During the period of observation, combined therapy did not modify BM fibrosis; however, an increase in CD34+ sinusoids and a decrease in CD34+ hemopoietic cells were noted.

Haemopoietic defect and decreased expansion potential of bone marrow autografts from patients with acute myeloid leukaemia in first remission.

Autologous bone marrow (BM) transplantation for acute myeloid leukaemia (AML) in complete remission (CR) is frequently followed by a slow haemopoietic recovery. We assessed the haemopoietic capacity of purified BM stem cell (CD34+ DR-) and progenitor cell (CD34+ DR+) populations from patients with AML in CR, and compared these data with those of normal BM. The feasibility of ex vivo expansion in stroma-conditioned medium supplemented with cytokines was also investigated. The number of CFU-GM produced by initial patient CD34+ DR- cells was decreased compared to normal, whereas these values were similar to normal for CD34+ DR+ cells. BFU-E, HPP-CFC and LTC-IC were reduced for both patient CD34+ DR- and CD34+ DR+ subpopulations. In contrast to normal, the patient CD34+ DR- fraction was not enriched in LTC-IC. CFU-GM expansion from patient CD34+ DR- cells was poor and decreased after 14 d of culture. No HPP-CFC expansion could be observed for patient cells. LTC-IC were below the level of detection after 14-21 d of expansion culture of CD34+ DR- patient cells, whereas they were variably maintained or expanded for normal cells. After expansion culture, cytogenetic and/or FISH analyses did not reveal the anomalies present at diagnosis, regardless of the cell subpopulation analysed. In conclusion, BM cells of patients with AML in CR show a profound defect at the level of a stem cell enriched population. No meaningful ex vivo expansion could be obtained in culture conditions allowing for a significant expansion from a normal stem cell population.

In vitro evaluation of the haemopoietic defect of CD34+ cells from patients with acute myeloid leukaemia in first remission.

Haemopoietic cells from patients with acute myeloid leukaemia (AML) in first complete remission (CR1) show in vitro a haemopoietic defect and a decreased expansion potential. To better characterize this haemopoietic defect, CR1 AML and normal CD34+ cells were analysed for immunophenotype, viability, cell cycle and progenitor content before and during expansion culture in stroma-conditioned medium supplemented with cytokines. The production of haemopoiesis inhibitor by patient cells and the influence of high concentrations of stem cell factor (SCF) and Flt3-ligand (FL) on cell survival and ex vivo expansion potential were also studied. Before expansion, patient CD34+ cells showed viability and cell-cycle phase distribution similar to normal but lower percentages of CD34+DR- or CD34+CD38- cells and lower progenitor content. After 48 h of culture +/-30% of patient cells had died regardless of the cytokine combination used, whereas only 15% of normal cells died. After 7 d of culture, viability and cell cycle analyses showed comparable data for normal and patient samples. Co-culture of patient and normal cells did not show any evidence for haemopoiesis inhibitor production by patient cells. Even at high cytokine concentrations, a low progenitor expansion and a decrease in CD34+ cell numbers was observed for patient samples in contrast to normal samples. In conclusion, CR1 AML CD34+ cells showed excessive early cell mortality. No evidence for cell-cycle arrest or haemopoiesis inhibitor production was shown. SCF and FL used at high concentrations did not correct the patient cell expansion defect.

[Hematopoietic recovery as a function of the number of autografted CD34+ cells: a retrospective study of 66 patients with malignant hematologic diseases]. / Reprise Hématopoïétique en fonction du nombre de cellules CD34+ autogreffées: étude rétrospective chez 66 patients atteints d'hémopathies malignes.

Engraftment in relation to infused CD34+ cell number was retrospectively analysed in 66 patients with hematological diseases: non-Hodgkin's lymphoma (n = 33), multiple myeloma (n = 21), acute myelogenous leukemia (n = 7), Hodgkin's disease (n = 4) and myelodysplastic syndrome (n = 1). Progenitor cells were mobilized with rhG-CSF, alone or in association with chemotherapy. The cells were harvested by leukapheresis until at least 2 x 10(6) CD34+/kg body weight were obtained. A total of 194 leukaphereses were performed (median = 3 per patient, range 1-9). A median of 3.40 x 10(8) nucleated cells/kg (range 0.31-27.59) and a median of 7.15 x 10(6) CD34+ cell/kg (range 1.31-115.70) were transplanted. Regardless of transfusional support or patient diagnosis, engraftment was rapid in patients who had received > or = 5 x 10(6) CD34+ cell/kg. In this case, absolute neutrophil blood count > or = 0.5 x 10(9)/l was obtained on day 12 post graft (range 7-19) and platelet count > or = 20 x 10(9)/l was also reached after the same median time interval (range 8-121). From the present results, a minimal threshold of 5 x 10(6) CD34+ cell/kg appears to be suitable for providing rapid and complete hematopoieitc reconstitution in patients exposed to high doses of chemotherapy with or without total body irradiation. Furthermore, administration of rhG-CSF during post-graft period significantly decreased the neutrophil time recovery (P = 0.002) but not that of platelets (P > 0.05).

Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor.

The 67 kD laminin receptor (67LR) binds laminin-1 (LN), major component of the basement membrane, with high affinity. In this study, we demonstrated that human multiple myeloma cell lines (HMCL) and murine 5T2MM cells express 67LR. CD38(bright+) plasma cells in fresh multiple myeloma (MM) bone marrow (BM) samples showed weaker 67LR expression, but expression increased after direct exposure to a BM endothelial cell line (4LHBMEC). LN stimulated the in vitro migration of 3 HMCL (MM5.1, U266 and MMS.1), primary MM cells and the murine 5T2MM cells. 67LR has been shown to mediate the actions of LN through binding to CDPGYIGSR, a 9 amino acid sequence from the B1 chain of LN. MM cell migration was partially blocked by peptide 11, a synthetic nonapeptide derived from this amino sequence and also by a blocking antiserum against 67LR. Co-injection of peptide 11 with 5T2MM cells in a murine in vivo model of MM resulted in a decreased homing of 5T2MM cells to the BM compartment. In conclusion, LN acts as a chemoattractant for MM cells by interaction with 67LR. This interaction might be important during extravasation of circulating MM cells.

Meropenem versus ceftazidime as empirical monotherapy for febrile neutropenic cancer patients.

A total of 101 cancer patients with 121 febrile neutropenia episodes were randomised to receive empirical treatment with i.v. meropenem (1g/8 h) or ceftazidime (2 g/8 h). After 3 days, 89% of patients were on unmodified therapy in the meropenem group, compared with 83% in the ceftazidime group. Of the evaluable episodes (n = 106), the success rate with unmodified empirical therapy until the end of the treatment course was slightly higher with meropenem than with ceftazidime (48% vs 38%, P=0.39). Furthermore, initial success with further infections was observed in 22% of episodes treated with meropenem and in 13% of episodes treated with ceftazidime. Glycopeptides were used as first modification in 28% and 39% of meropenem and ceftazidime recipients, respectively. Both treatments were well tolerated and there were no reports of drug-related nausea/vomiting or seizures. No significant differences in response rate or in tolerability were observed when analysing only the first febrile episodes. In conclusion, meropenem seems to be as efficacious and well tolerated as ceftazidime and may be associated with a lesser requirement for the addition of glycopeptides.