[Palatal necrosis due to cocaine abuse]. / Nécrose palatine par consommation de cocaïne.

The easier access to cocaine allows chronic and intensive consumption. Nasally inhaled cocaine causes important midfacial lesions called: Cocaine Induced Midline Destructive Lesions. These lesions are due to several factors, the anesthetic, vasoconstrictive, locally prothrombotic properties of cocaine and its components combined with cytotoxic effects and traumatic nasal injuries related to consumption mode. Functional signs are: nasal regurgitation, rhinolalia, rhinorrhea, and midfacial pain. The morphological modifications of the nasal pyramid feature the destruction of bone and cartilage structures. Endo-buccal examination, anterior rhinoscopy, and TDM reveal palatine necrosis of variable extension. Nasal fossae superinfection is always present. Sinus superinfection is frequent. Management is multidisciplinary. Weaning must be achieved before surgery. It is necessary to rehabilitate speech and swallowing functions by the means of various local or free flaps.

Chemotherapeutic sensitivity of normal and leukemic hematopoietic progenitor cells to N-[4-(9-acridinylamino)-3-methoxyphenyl]-methanesulfonamide, a new anticancer agent.

The sensitivities of hematopoietic colony-forming cells (CFC) to N-[4-(9-acridinylamino)-3-methoxyphenyl]-methanesulfonamide (NSC-249992) (m-AMSA) were measured with an in vitro clonogenic assay, a modification of the Robinson and Pike human marrow culture system. CFC derived from bone marrow and peripheral blood of normal subjects and patients with chronic myeloid leukemia (CML) were studied. Sensitivities to m-AMSA did not differ significantly between normal marrow and blood CFC, between normal and CML CFC, or between CML CFC obtained from patients with leukemias in chronic phase and blast transformation. Drug doses and exposure times producing in vitro hematopoietic inhibition were comparable to clinically employed drug dosages and schedules associated with hematopoietic toxicity.

Ex vivo expansion of megakaryocyte progenitor cells: cord blood versus mobilized peripheral blood.

Thrombocytopenia is a problematic and potentially fatal occurrence after transplantation of cord blood stem cells. This problem may be alleviated by infusion of megakaryocyte progenitor cells. Here, we compared the ability of hematopoietic progenitor cells obtained from cord blood and expanded in culture to that of mobilized peripheral blood cells. The CD34(+) cells were plated for 10 days in presence of thrombopoietin (TPO) alone and combined with stem cell factor (SCF), Flt3-ligand (FL), interleukin-3 (IL-3), IL-6, and IL-11. Cells were analyzed for the CD41 and CD42b expression and for their ploidy status. Ex vivo produced platelets were enumerated. We show that (1) TPO alone was able to induce differentiation of CD34(+) cells into CD41(+) cells, with limited total leucocyte expansion; (2) the addition of SCF to TPO decreased significantly CD41(+) cell percentage in CB, but not in MPB; and (3) in CB, the addition of FL, IL-6, and IL-11 to TPO increased the leukocyte expansion with differentiation and terminal maturation into MK lineage. In these conditions, high numbers of immature CD34(+)CD41(+) MK progenitor cells were produced. Our results thereby demonstrate a different sensitivity of CB and MPB cells to SCF, with limited CB MK differentiation. This different sensitivity to SCF (produced constitutively by BM stromal cells) could explain the longer delay of platelet recovery after CB transplant. Nevertheless, in CB, the combination of TPO with FL, IL-6, and IL-11 allows generation of a suitable number of immature MK progenitor cells expressing both CD34 and CD41 antigens, which are supposed to be responsible for the platelet recovery after transplantation.

Decreased production of cytokines after cytomegalovirus infection of marrow-derived stromal cells.

Cytomegalovirus (CMV) infection is frequently associated with graft failure in bone marrow transplant patients; the pathogenesis of this myelosuppression in not clearly understood. We have previously documented that CMV-induced myelosuppression is related to an alteration of the marrow microenvironment. To further investigate the effect of CMV on stromal cell function, conditioned media (CM) from CMV-infected or uninfected stromal cells were tested for their capacity to promote the growth of granulocyte/macrophage colony-forming cells (CFU-GM) and for their concentration in colony-stimulating factors (CSFs) such as interleukin-3 (IL-3), IL-6, granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF and G-CSF). CM from CMV-infected stromal cells failed to sustain granulocyte-macrophage colony-forming unit (CFU-GM) growth. The production of IL-6, GM-CSF, and G-CSF, measured by enzyme-linked immunosorbent assay (ELISA), was 21,150 +/- 3392, 57 +/- 15, and 2340 +/- 717 pg/mL, respectively, in CMV-infected stromal cells stimulated by lipopolysaccharide (LPS) and was significantly decreased (p < 0.01) from the control values (177,138 +/- 98,692, 113 +/- 20, and 5533 +/- 1306 pg/mL). These results suggest that the myelosuppressive effect of CMV is primarily due to a lack of CSF production. To further document this hypothesis, primitive marrow progenitor cells (blast colony-forming cells [Bl-CFC]) cultured on CMV-infected stromal layer have been grown in the presence of IL-3 (20 ng/mL), IL-6 (20 ng/mL), GM-CSF (40 ng/mL), and G-CSF (50 ng/mL). Used alone, all these CSFs partially reverse the CMV-induced inhibition of Bl-CFC growth; the combination of these CSFs completely restores normal Bl-CFC values. These data strongly suggest that CMV-induced myelosuppression is related to the lack of CSF production by the cells of the marrow microenvironment.

Prevention of CMV-induced myelosuppression by anti-CMV antibodies: an in vitro model.

Pathogenesis of cytomegalovirus (CMV)-induced myelosuppression is not clearly understood and could be related to a direct toxic effect on the marrow progenitors and/or an alteration of the marrow environment. Myeloid progenitors (granulocyte-macrophage colony-forming units, CFU-GM) were not affected by incubation with increasing titers of CMV (10-10(5) plaque-forming units [pfu]/ml) during 2-6 h. By contrast, using the blast colony-forming cell (Bl-CFC) assay, we confirmed that CMV induced myelosuppression through an alteration of the marrow-derived stromal layer. Using this experimental model, we compared the capacity of nonspecific human immunoglobulins (IgG), specific polyclonal anti-CMV IgG, and a human monoclonal anti-CMV IgG to prevent the myelosuppressive effect of 10(4) pfu/ml of CMV. Specific anti-CMV IgG (polyclonal or monoclonal) at the concentration of 10 micrograms/ml were able to prevent the CMV-induced myelosuppressive effect, whereas nonspecific human IgG was not effective in this model. Our results suggest that 1) CMV-induced myelosuppression is related to an alteration of the marrow microenvironment, 2) specific monoclonal and polyclonal anti-CMV IgG prevent this myelosuppressive effect in vitro, and 3) human monoclonal anti-CMV IgG could be useful in vivo in the immunoprophylaxis of CMV infections.

Comparison of in vitro inhibition of etoposide (VP16) on leukemic and normal myeloid, erythroid clonogenic cells.

We have compared in various clonogenic assays the in vitro sensitivity to etoposide (VP16) of 1) human leukemic precursors (leukemia colony-forming units; L-CFU), 2) normal erythroid progenitors (erythroid burst-forming units; BFU-E, and 3) normal committed myeloid progenitors (granulocyte-macrophage colony-forming units; CFU-GM and more primitive hemopoietic precursors (PPC) that adhere to cultured marrow stromal cells. Bone marrow samples were obtained from 15 normal subjects and 16 leukemic patients: 9 in the acute phase of acute nonlymphoblastic leukemia (ANLL) and 7 in complete remission. VP16 was tested at concentrations ranging from 10(-8) to 10(-3) M. The median recoveries at 10(-3) M VP16 were respectively 0%, 0.5%, 0%, and 0% for leukemic progenitors, CFU-GM from leukemic patients in complete remission, normal CFU-GM, and BFU-E, and 23% for PPC. This indicates that CFU-GM, BFU-E, and L-CFU are highly sensitive to VP16, whereas PPC, more primitive myeloid precursors, are spared. These results suggest that VP16 may be used as an "ex vivo" purging agent for autologous bone marrow.

Production of human monoclonal IgG antibodies reacting with cytomegalovirus (CMV).

A human monoclonal antibody (MoAb) reacting with cytomegalovirus (CMV) has been produced using somatic cell hybridization between Epstein-Barr virus (EBV) infected B lymphocytes and a human-mouse heteromyeloma cell line (SHM-D33). The hybrids were selected in HAT medium containing 5 x 10(-7) ouabain. The median level of Ig production was 5 (0.1-20) micrograms/10(6) cells/day. One selected hybridoma (IB-8E9H5) has been maintained in continuous culture for more than 30 months with a stable IgG2, lambda production. Molecular hybridization using EBV-specific probes demonstrate that our hybrids have lost the IR-1 EBV sequence during fusion. Unexpectedly, these blotting experiments revealed the presence of multiple EBNA-1 sequences dispersed among the genomic DNA of the SHM-D33 cell line. Screening for anti-CMV specificity was performed by ELISA and confirmed by immunofluorescence staining. Thus far, three CMV reference strains and 14 local strains are stained by the MoAb as early as 3 h after CMV infection of human fibroblasts, apparently through the recognition of a nuclear viral antigen of 67 kDa. In conclusion, this technique permits (a) the removal of the EBV genome contained in the lymphoblastoid parental cell line and (b) the production of human anti-CMV MoAb with potential applications in the prevention of life threatening CMV infections.

Effect of 4-hydroperoxycyclophosphamide on leukemic and normal human myeloid progenitor cells.

The sensitivity of myeloid progenitor cells from normal subjects (N-CFU-GM) and from leukemic patients in complete remission (LR-CFU-GM) to 4-hydroperoxycyclophosphamide (4-HC) were compared to the sensitivity of leukemic progenitor cells (L-CFU) to this drug. The results were expressed as the dose of 4-HC needed to kill 90% (TD 90) of the progenitor cells. The mean TD 90 were respectively for N-CFU-GM : 59 (+/- 11 S.E.M.) nM ml-1 and for L-CFU 79 (+/- 6 S.E.M.) nM ml-1. Thus, L-CFU were equally sensitive to 4-HC as N-CFU-GM. Moreover, the mean TD 90 for LR-CFU-GM was 87 (+/- 5 S.E.M.) nM ml-1. Thus, the sensitivity of N-CFU-GM and LR-CFU-GM did not differ significantly from that of L-CFU. These results are not encouraging for the use of 4-HC in vitro to eliminate the residual leukemic cells from autologous bone marrow of AML patients in complete remission. The sensitivity of L-CFU was modified neither by previous cytoreductive therapy (different from cyclophosphamide) nor by the time elapsed since diagnosis of AML.

Characterization of CD34+ subsets derived from bone marrow, umbilical cord blood and mobilized peripheral blood after stem cell factor and interleukin 3 stimulation.

We characterized CD34+ cells purified from bone marrow (BM), mobilized peripheral blood (PB) and cord blood (CB) and we tried to establish correlations between the cell cycle kinetics of the CD34+CD38- and CD34+CD38+ subpopulations, their sensitivity to SCF and IL-3 and their expression of receptors for these two CSFs. At day 0, significantly fewer immature CD34+CD38- cells from CB and mobilized PB are in S + G2M phases of the cell cycle (respectively 2.0 +/- 0.4 and 0.9 +/- 0.3%) than their BM counterpart (5.6 +/- 1.2%). A 48-h incubation with SCF + IL-3 allows a significant increase in the percentage of cycling CD34+CD38- cells in CB (19.2 +/- 2.2%, P < 0.0002) and PB (14.1 +/- 5.5%, P < 0.05) while the proliferative potential of BM CD34+CD38- progenitors remains constant (8.6 +/- 1.0%, NS). CD123 (IL-3 receptor) expression is similar in the three sources of hematopoietic cells at day 0 and after 48-h culture. CD117 (SCF receptor) expression, although very heterogeneous according to the subpopulations and the sources of progenitors evaluated, seems not to correlate with the difference of progenitor cell sensitivity to SCF nor with their proliferative capacity. Considering the importance of the c-kit/SCF complex in the adhesion of stem cells to the microenvironment, several observations are relevant. The density of CD117 antigen expression (expressed in terms of mean equivalent soluble fluorescence, MESF) is significantly lower on fresh PB cells than on their BM (P < 0.017) and CB (P < 0.004) counterparts, particularly in the immature CD34+CD38- population (560 +/- 131, 2121 +/- 416 and 1192 +/- 129 MESF respectively); moreover, when PB and BM CD34+CD38- cells are stimulated for 48 h with SCF + IL-3, the CD117 expression decreases by 1.5- and 1.66-fold, respectively. This reduction could modify the functional capacities of ex vivo PB and BM manipulated immature progenitor cells.

Donor lymphocyte infusions in adult haploidentical transplant: a dose finding study.

Haploidentical transplantation has become a clinical option for patients lacking a compatible donor. However, patients are still referred at advanced stages and are usually heavily pretreated. This results in a high risk of toxicity, relapses and infections. We therefore started a donor lymphocyte infusion (DLI) dose-finding protocol, to try to improve both relapse rate and immunity reconstitution. In all, 12 consecutive patients were investigated. All had a refractory, some progressive, disease. Conditioning consisted of TBI, melphalan, ATG, fludarabine and CSA pretransplant. In four rapidly progressive patients, Ara-C had to be given 1 week preconditioning. The graft was T- and B-cell depleted with a fixed reinfused CD3 dose of 5 x 10(4)/kg. All patients engrafted before day 20. G-CSF was given from day 5 post-transplant and replaced with GM-CSF in the last three patients. Nonrelapse related mortality was 0/12 at 1 year. DLI were started at day 28 (3 x 10(4) CD3/kg) in the two first patients. This resulted in acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) in both, but they did not relapse. The next dose was 1 x 10(4)/kg monthly for 3 months. This was well tolerated with only one grade I GVHD. Given the high relapse rate, we escalated doses (1, 3 and 10 x 10(4)/kg). This produced GVHD in all. We next moved, to GM-CSF and 1 x 10(4) CD3/kg monthly. Overall, 6/12 patients relapsed and received therapeutic DLI, starting at 1 x 10(5) CD3/kg with escalation every 2 weeks. We conclude that prophylactic DLI are feasible in adult haploidentical transplantation, without GVHD at a monthly dose of 1 x 10(4) CD3/kg. They result in faster CD4 recovery and a low rate of infections. The impact of GM-CSF remains to be further investigated. This scheme seems ideal for patients transplanted early in the course of their disease. In very bad prognosis patients, it remains insufficient to rapidly induce a GVL effect. Escalated doses are feasible but the price is aGVHD. Therapeutic DLI can be given at higher doses, depending on the time post-transplant. Haploidentical transplantation with low-dose DLI is a safe procedure that should be considered in all patients needing a transplant, but lacking a matched donor, early in the course of the disease.

Circadian and seasonal variations of hematopoiesis in cord blood.

Cord blood hematopoietic progenitors undergo circadian and seasonal variations. The lowest values are obtained between 4:00 and 12:00, as well as between May and August. This represents the first observation of such rhythms before birth.

Lactoferrin: its role as a regulator of human granulopoiesis?

Lactoferrin has been proposed recently as a physiological regulator of the granulocyte-monocyte progenitor (CFU-GM). This glycoprotein, when saturated with iron, has been said to limit the CFU-GM growth by decreasing production and release of colony stimulating activity by monocytes and macrophages. Human milk lactoferrin saturated with iron, at concentrations ranging from 10(-8) M, was added either to endogenously stimulated bone marrow cells or to mononucleated cells used as feeder layers for adherent cell-depleted marrow. Irrespective of the concentration of lactoferrin within the culture system used, no significant inhibition of the CFU-GM growth was observed. Moreover, the CFU-GM stimulating activity of medium conditioned by a 4 day incubation of 1 X 10(6) mononucleated blood cells in the presence or in the absence of lactoferrin was the same. Various possible explanations for not confirming the reported inhibiting activity of iron-saturated lactoferrin were explored: (a) masking inhibition of the system by prostaglandin E2 (PGE2), (b) masking inhibition of the system by bovine lactoferrin present in the fetal calf serum, (c) preinhibition of the system by leukemic-associated inhibitory activity possibly present in the culture system, (d) the iron and calcium content of the culture medium used, (e) the fixation of lactoferrin to plastic compounds, (f) the source of the human lactoferrin used, and (g) the marrow cell separation methods used. None of these factors was shown to play a role in vitro in the activity of lactoferrin and thus no evidence was found for a significant role of lactoferrin in the regulation of human granulopoiesis.

TGF-beta activity and expression of its receptors in B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in Western countries and results from the accumulation of B-lymphocytes which are functionally abnormal and predominantly non-cycling in vivo. Consequently, it is important to understand why B-CLL cells accumulate in GO phase. Since TGF-beta is an important negative regulator of the immune system, a loss of responsiveness to this factor might provide a selective advantage to B-CLL cells. Here we review data on the role of TGF-beta in B-CLL. We show that the B-CLL cell response to TGF-beta signals is abnormal in vitro (inhibition of proliferation and induction of apoptosis). This lack of response of B-CLL cells to TGF-beta inhibition appears to be accompanied by a decrease or a loss of TGF-beta receptor expression.

Adhesion to bone marrow stroma inhibits apoptosis of chronic lymphocytic leukemia cells.

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of monoclonal long-lived B cells which are apparently resistant to normal apoptotic regulation. Since bone marrow stromal cells play an essential role in B lymphopoiesis, we have investigated whether stromal cells influence B-CLL cell survival. Our results indicate that intimate contact with stromal cells reduces B-CLL cell apoptosis and prevents the loss of bcl-2 protein expression. Binding of B-CLL cells to stromal cells requires simultaneous action of beta1 and beta2 integrins. The interaction between B-CLL cells and other cell types seems important for their survival and may represent an important mechanism underlying accumulation of malignant cells in B-CLL patients.

Comparative analysis of cytokines released by bone marrow stromal cells from normal donors and B-cell chronic lymphocytic leukemic patients.

We studied the production of cytokines (G-CSF, GM-CSF, IL-6, LIF and IL-10) by bone marrow stromal cells of five untreated patients with B-CLL, in Rai stage 0, I and II, and of 8 healthy subjects. The production of G-CSF, GM-CSF, LIF and IL-10 did not differ significantly between controls and B-CLL patients. However, the ability of stromal cells to release IL-6 in response to LPS was decreased in all patients: 36 +/- 5 ng/ml versus 123 +/- 47 ng/ml for normal controls (p < 0.004). Moreover, a soluble activity that inhibited hematopoietic colony formation was detected in B-CLL stromal cell conditioned media. Some potential inhibitors were envisaged and the results indicated an increased production of TGF-beta by B-CLL stromal cells compared to normal stromal cells (respectively 53 +/- 10 versus 15 +/- 4 ng/ml, p < 0.03). The reduced capacity of B-CLL stromal cells to produce IL-6 was associated with this excessive release of TGF-beta; indeed, addition of anti-TGF-beta neutralizing antibody to B-CLL stromal cells, before LPS stimulation, totally normalized the production of IL-6. TGF-beta and IL-6 were also measured in serum samples from normal subjects and B-CLL patients. No significant difference was seen in the production of total TGF-beta (bioactive and latent forms) between normal and B-CLL sera but the mean level of bioactive protein in B-CLL sera was increased in comparison with normal sera (1.74 +/- 0.44 versus 0.67 +/- 0.2 ng/ml, p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of Soluble Interleukin 2 Receptor in Sera of Adult Patients with Hematological or Solid Malignancies.

Interleukin 2 (IL-2) exerts its biological activity through a specific membrane receptor. Using specific monoclonal antibodies directed against the IL-2 receptor, a soluble form of this receptor can be detected in the serum. This soluble part of the human IL-2 receptor (sIL-2R) is released by T and B lymphocytes and plays a role in lymphoid cell growth regulation. We have measured the sIL-2R by ELISA in the serum of patients with solid tumors and with hematological malignancies (44 chronic lymphocytic leukemias (CLL), 5 hairy cell leukemias (HCL), 14 Hodgkin's diseases (HKD), 34 non-Hodgkin's lymphomas (NHL) and 19 acute lymphoblastic leukemias (ALL). The mean sIL-2R level in 40 normal subjects was 173 + 168 U/ml (mean {pminus} SD). It was considerably increased in HCL: 17938 {pminus} 23748 (P < 0.0003). In CLL, a significant increase was found which was particularly pronounced at clinical stage III and IV with a mean level of 1299 {pminus} 1127 U/ml. In HKD, sIL-2R was slightly but significantly increased 519 + 524 U/ml (P < 0.0004). In NHL, the sIL-2R level was 1015 {pminus} 1022 U/ml, but this increase did not correlate with the clinical stage or the histological grade of the disease. In ALL, sIL-2R levels were also significantly increased 1633 + 1046 U/ml (P < 0.00001). In 69 patients with solid tumors (including lung carcinomas, gynecological and digestive malignancies), 39% of the patients tested had slightly increased sIL-2R levels. However, this increase, when present, could not be related to the tumor histology. These results suggest that sIL-2R measurement is a poor diagnostic marker for solid tumors and some lymphoproliferative disorders. However, in patients with hematological malignancies, it could be a useful tool to monitor lymphoid neoplasias.

Myeloid and lymphoid recovery following allogeneic bone marrow transplantation: a comparative study between related, unrelated bone marrow and allogeneic peripheral stem cell transplantation.

We studied myeloid and lymphoid recovery during a period of 12 months following HLA matched allogeneic bone marrow transplantation (BMT) in 15 patients. Patients were divided into three groups. Each group contained 5 patients according to the source of hematopoietic stem cell transplantation (HST): 1) related bone marrow transplantation (BMT), 2) allogeneic peripheral blood stem cell transplantation (PBSCT) and 3) matched unrelated donor transplantation (MUD). The rate and pattern of recovery of granulocytes, lymphocytes (T-cell subsets, B-cells, NK cells, subsets of CD45) were studied by cell counting and flow cytometry. Our results suggest faster recovery of PMN after PBSCT. Higher CD4 cell counts observed in the PBSCT group may have an impact on a lower incidence of opportunistic infections. Chronic GvHD mediated GvL effect seems to be more important in blood stem cell transplanted patients and this may have an influence on disease free survival.

Nocodazole entrapped into liposomes: no more effect on human CFU-C than free nocodazole.

Nocodazole, a water insoluble antimitotic drug active on L1210 leukemia was incorporated into liposomes, to investigate whether this procedure could increase cellular uptake. The effects of micronized nocodazole and liposome-entrapped nocodazole were compared on human marrow cells in vitro using a myeloid progenitor cell assay (CFU-C). The human CFU-C were sensitive to the micronized drug in a dose-related fashion. However, contrasting with a previous report on L 1210 leukemia, entrapping of nocodazole into liposomes did not increase its activity of CFU-C of either normal or leukemic subjects.

[Hematopoietic stem cells: source, indications and perspectives]. / Les cellules souches hématopoiétiques: sources, indications et perspectives.

The haematopoietic stem cell (HSC) has been first described in the mouse and now identify in human as well. Exposed to a cocktail of growth factor, this HSC can self re-new and/or differentiate into the three lineages we have in the peripheral blood. These HSC are of major importance in the clinics since they can be used for some marrow (or stem cell) transplantation, and lead to the cure of a number of malignant and non malignant hemopathies. We have today three sources of HSC: the bone marrow, the mobilized peripheral blood stem cell and the cord blood. Bone marrow used to be the classical source of HSC after harvesting by aspirations in the iliac crest. However, this approach is now supplanted by the recovery of HSC in peripheral blood using a cell separation after four days of G-CSF administration. These are several advantages of this technique, but the most important one is the more rapid hematopoietic recovery after transplantation, reducing the risk of infection and transfusion. A recent source of HSC is the umbilical cord blood. At the moment of delivery, the cord blood is extremely enriched in HSC due to the migration of these cells from the liver to the bone marrow stroma, where they will persist after birth. We have learned that the marrow stroma display a major role in the regulation of hematopoiesis and the pathogenesis of several malignant hemopathies can be explained by disturbance in the function of stromal cell. We have particularly studied the patho-genesis of chronic lymphocytic leukaemia. We have also observed that a subpopulation of stromal cells, the mesenchymal cells are of major importance in the microenvironment. In addition, the plasticity of these cells is demonstrated in vitro and we have currently a research program investigating its differentiation in neural cells. All these observations bring new promises in the treatment of hemopathies but also in some other neurological degenerative diseases.

[Adoptive immunotherapy with interleukin 2. Initial results of a pilot study in 6 cancer patients]. / Immunothérapie adoptive par interleukine-2. Premiers résultats d'une étude pilote chez 6 malades cancéreux.

Adoptive immunotherapy of cancer consists of using interleukin-2 to induce the formation of lymphokine-activated killer (LAK) cells which are toxic to tumoral cells. Six patients, 3 with hypernephroma and 3 with melanoma, were treated with interleukin-2. Drug toxicity consisted of capillary leakage syndrome in one case and reversible renal impairment in another. One patient showed an objective response; transient subjective improvement was observed in all patients.