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Resume Introduction Les lymphomes malins non hodgkiniens exprimant le recepteur T gamma delta pour l'antigene (GDTL) sont un groupe rare et heterogene de lymphomes atteignant principalement la rate et le foie et plus rarement la peau, l'intestin ou la region nasale. Nous rapportons un cas exceptionnel de GDTL avec atteinte meningee exclusive revele par une dermatomyosite. Exegese Un homme de 64 ans atteint de dermatomyosite developpe une paraparesie et une surdite. L'analyse du liquide cephalorachidien revele la presence de grandes cellules lymphomateuses CD3+ CD4– CD8– CD7+ CD16– CD56– et exprimant le recepteur pour l'antigene des lymphocytes T gamma delta. Aucune atteinte lymphomateuse extrameningee n'est mise en evidence. Ce cas est doublement interessant car il s'agit, d'une part du premier cas de dermatomyosite revelant un GDTL, d'autre part du premier cas de GDTL avec atteinte primitive et selective des meninges. Conclusion Le GDTL doit etre ajoute a la liste des neoplasies associees a la survenue d'une dermatomyosite. De plus, une possible atteinte exclusive des meninges par un GDTL doit etre connue du clinicien.

BACKGROUND: RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type. STUDY DESIGN AND METHODS: An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n = 64) or a myeloablative conditioning regimens (MAC; n = 46). Patients received marrow (n = 64) or PBPCs (n = 46). RESULTS: Overall, intensity of conditioning regimen (RIC vs. MAC; p = 0.0005) and graft source (PBPC vs. marrow; p < 0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p = 0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p < 0.0001) and the dose of ATG (p = 0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC. CONCLUSION: Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.

PNH is a disorder of the pluripotent stem cells resulting in a deficient expression of membrane-bound GPI-anchored proteins in different cell types. Several flow cytometric approaches are designed to detect this antigen deficiency. But they all require drawing and testing of normal samples as control. Therefore, in the present study two flow cytometric assays for the detection of CD55 and CD59 deficiency in erythrocytes (REDQUANT CD55/CD59) and granulocytes (CELLQUANT CD55/CD59) are proposed. Precalibrated beads are used to define the cut off between normal and deficient cell populations. The specificity of the tests has been evaluated in healthy blood donors (n=52) resulting in a clear and reproducible cut off (3%) for the normal percentage of GPI-deficient cells. This cut off has been confirmed in leukaemia and lymphoma patients not suspected for developing PNH. The sensitivity has been tested in patients suffering from known PNH (n=23). Both tests performed in combination allowed a reliable detection of PNH in all patients showing antigen deficiencies in both cell types in most patients (20/23). In contrast, the PNH clones in the investigated patients with MDS (4/19) or AA (4/22) were present in granulocytes or erythrocytes, only. This underlines the necessity of analysing erythrocytes as well as granulocytes. Preliminary data regarding a possible correlation between disease activity and percentage of antigen-deficient cells lead to the assumption that haemolytic crises can only be determined on granulocytes whereas deficient erythrocytes disappeared due to complement-mediated lysis of the PNH clone. In conclusion, the combination of the test kits enables the differential diagnosis of PNH clones in a standardized, simple and rapid approach which may have therapeutic consequences.

Through two clinical studies, tumor cells were searched for in the bone biopsies and cytapherisis of patients suffering from inflammatory tumors and who had undergone intensive therapy and autografts (Pegase 2 program). In these studies we used immunocytochemical test with two monoclonal antibodies. The results have shown the presence of tumor cells in 14% of the patients (respectively 18%), with no correlation to the appearance of metastases after 4 years in the first study. Nevertheless, the presence of these tumor cells seems to be an important factor in the number of relapses. It seems important to develop research into tumor contamination especially in the selection of grafts over the next few years.

Summary Objective To describe the outcome of an unselected large series of patients with lymphoblastic lymphoma (LBL) treated in a single institution. Patients and methods Sixty-two patients were treated between 1980 and 1992. Induction chemotherapy (CT) to achieve complete response (CR) was: French Multicenter Acute Lymphoblastic Leukemia (ALL) protocols (38), non-Hodgkin’s Lymphoma (NHL) protocols (20). Thirty patients underwent transplant after achieving CR (allogeneic 12; autologous 18). Results Forty-six patients (74%) achieved CR and 16 (26%) failed to respond. The patients who received an ALL induction had an 89% CR rate, while the CR rate was 52% in patients who received a NHL-like regimen. With a median follow-up of 93 months (range 36–187), the actuarial overall survival (OS) rate for all patients is 49% at five years and 41% at 10 years, and the actuarial event-free survival (EFS) rate is 45% and 37%. OS and EFS in the grafted population are, respectively, 60% and 56% at five years. Our results also show a trend toward a longer OS in allografted group. Conclusions ALL induction therapy is more effective than the NHL-like regimen for augmenting the CR rate. Autologous or allogeneic transplantation should be considered as consolidation therapy in high-risk group patients.

Resume La leucemie myeloide chronique (LMC) est une proliferation clonale d'une cellule immature qui touche les lignees my eloide, erythroide, megacaryocytaire, lymphoide B et les cellules natural killer (NK). Le caryotype met en evidence de facon presque constante le chromosome Philadelphie (Ph). Cette anomalie est due a une translocation reciproque entre les chromosomes 9 et 22, t (9;22) (q34;q11), qui genere deux chromosomes anormaux 9q+ et 22q-, ce dernier etant designe ≪ chromosome Ph ≫. Les points de cassure chromosomiques impliquent le protooncogene c- ABL sur le chromosome 9 et le gene BCR (pour breakpoint cluster region ) sur le chromosome 22. La translocation aboutit a un gene de fusion BCR/ABL , dont l'ARNm hybride permet la synthese d'une proteine de fusion de 210 kDa ou 190 kDa selon le point de cassure dans la region bcr. Cette proteine joue un role central dans la LMC, en premier lieu par son activite tyrosine-kinase accrue. Neanmoins, la perte des capacites de regulation negative de la croissance cellulaire par ABL et l'interaction de BCR/ABL avec d'autres genes ( RAS ou c- MYC par exemple) sont probablement impliquees dans la physiopathologie de la LMC. Une meilleure comprehension des mecanismes moleculaires de la LMC pourrait aboutir a une therapie specifique par l'utilisation d'inhibiteurs des tyrosine-kinases, d'oligonucleotides antisens ou meme de proteines se liant au gene de fusion BCR/ABL et inhibant sa transcription.

Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I (MYST3 exon 16-CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.

Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's lymphomas. A rare entity within this group is represented by hepatosplenic T cell lymphoma, characterized by primary extranodal disease with infiltration of the liver and the spleen and by expression of the T cell receptor gamma delta chain.A 64-year old man with dermatomyositis developed rapid-onset paraparesia and deafness. Cerebrospinal fluid analysis revealed large granular lymphomatous cells with CD3+ CD4- CD8- CD7+ CD16- CD56- surface antigens, expressing the gamma delta T-cell receptor. There was no evidence of skin or bone marrow infiltration by lymphoma or any other involvement. This is the first report of dermatomyositis associated with a gamma delta T-cell lymphoma (GDTL). Moreover, primitive and isolated meningeal involvement of such lymphomas has never been described before.GDTL should be added to the differential list of neoplasia associated with dermatomyositis. Physiopathological mechanisms implicated in the neurological involvement of such lymphomas need to be elucidated.

RBCT (RBCT) requirements of stem cell transplant (SCT) recipients are often substantial and may be related to transplant type.An analysis was done of RBCT requirements and Hb recovery kinetic in the first 60 days after HLA-identical sibling allogeneic SCT in a series of 110 consecutive patients treated for various malignant diagnoses. Patients were prepared with either an antithymocyte globulin (ATG) and reduced intensity chemotherapy-based conditioning (RIC) (n=64) or a myeloablative conditioning regimens (MAC; n=46). Patients received marrow (n=64) or PBPCs (n=46).Overall, intensity of conditioning regimen (RIC vs. MAC; p=0.0005) and graft source (PBPC vs. marrow; p0.0001) independently predicted RBCT requirements. Hb recovery was accelerated after RIC when compared to MAC allo-SCT (p=0.02). In RIC patients, RBCTs were inversely correlated to Hb level before conditioning (p0.0001) and the dose of ATG (p=0.009). Moreover, Hb level before allo-SCT significantly influenced Hb recovery kinetic after RIC but had no impact on RBCT requirements and Hb recovery after MAC.Thus, RIC conditioning creates a different pattern of erythropoiesis recovery as compared to a MAC regimen and suggest a need for studies aimed at further reducing RBCT and accelerating Hb recovery.

Approaches using reduced conditioning regimens have been developed to obtain minimal procedure-related toxicity. Such novel therapeutic options are being explored with good preliminary results concerning feasibility and engraftment. However, many aspects remain under-evaluated and few data are available about immune and dendritic cell (DC) reconstitution after these highly immunosuppressive regimens. We present here our data in 20 patients receiving allogeneic bone marrow transplantation (allo-BMT) using a reduced preparative regimen. We evaluated in the first 3 months following allo-BMT, several immunological parameters including DC subsets, and compared these to historical results obtained in a group of myeloablative allo-BMT patients. We found an early recovery of leukocytes, CD8+ and NK lymphocytes. We also found a trend towards an improved B cell recovery. These results are somewhat in contrast to the altered immune recovery observed in the myeloablative setting. In addition, we found a significant early circulating DC recovery. Circulating blood DCs were also found to be of full donor origin as assessed by FISH in sex-mismatched pairs. Nevertheless, naive CD4 + CD45RA + T cells were found to be profoundly reduced following such regimens.Collectively, these data further enhance the overall benefits of reduced intensity regimens and the need for a stringent biological monitoring for assessment of the potential advantages of reduced intensity allo-BMT in comparison with conventional allo-BMT.

PNH is a disorder of the pluripotent stem cells resulting in a deficient expression of membrane-bound GPI-anchored proteins in different cell types. Several flow cytometric approaches are designed to detect this antigen deficiency. But they all require drawing and testing of normal samples as control. Therefore, in the present study two flow cytometric assays for the detection of CD55 and CD59 deficiency in erythrocytes (REDQUANT CD55/CD59) and granulocytes (CELLQUANT CD55/CD59) are proposed. Precalibrated beads are used to define the cut off between normal and deficient cell populations. The specificity of the tests has been evaluated in healthy blood donors (n=52) resulting in a clear and reproducible cut off (3%) for the normal percentage of GPI-deficient cells. This cut off has been confirmed in leukaemia and lymphoma patients not suspected for developing PNH. The sensitivity has been tested in patients suffering from known PNH (n=23). Both tests performed in combination allowed a reliable detection of PNH in all patients showing antigen deficiencies in both cell types in most patients (20/23). In contrast, the PNH clones in the investigated patients with MDS (4/19) or AA (4/22) were present in granulocytes or erythrocytes, only. This underlines the necessity of analysing erythrocytes as well as granulocytes. Preliminary data regarding a possible correlation between disease activity and percentage of antigen-deficient cells lead to the assumption that haemolytic crises can only be determined on granulocytes whereas deficient erythrocytes disappeared due to complement-mediated lysis of the PNH clone. In conclusion, the combination of the test kits enables the differential diagnosis of PNH clones in a standardized, simple and rapid approach which may have therapeutic consequences.

Breast cancer is the most frequent neoplastic disease in populations of developed countries. It will affect 1 of every 6 or 7 women during their lifetime. The disease eventually evolves to a metastatic stage, and currently appears to be not curable at that stage. Thus, understanding mechanisms that result in the establishment of tumor at sites distant from the primary location is of the utmost importance. Equally important is the definition of a metastatic state, especially in regard to the detection of micrometastases. Finally, the presence of circulating tumor cells in the peripheral blood of patients who undergo progenitor mobilization, collection and reinfusion may be of clinical significance in the setting of high-dose chemotherapy for breast cancer.

Acute promyelocytic leukemia (APL) is typified by the t(15;17), generating the PML-RAR alpha fusion and predicting a beneficial response to retinoids. However, a sizeable minority of APL cases lack the classic t(15;17), prompting the establishment of the European Working Party to further characterize this group. Such cases were referred to a workshop held in Monza, Italy and subjected to morphologic, cytogenetic, and molecular review, yielding 60 evaluable patients. In the majority (42 of 60), molecular analyses revealed underlying PML/RAR alpha rearrangements due to insertions (28 of 42) or more complex mechanisms, including 3-way and simple variant translocations (14 of 42). Metaphase fluorescence in situ hybridization (FISH) demonstrated that insertions most commonly led to formation of the PML-RAR alpha fusion gene on 15q. In 11 of 60 workshop patients, PLZF/RAR alpha rearrangements were identified, including 2 patients lacking the t(11;17)(q23;q21). In one case with a normal karyotype, FISH analysis revealed insertion of RAR alpha into 11q23, and PLZF-RAR alpha was the sole fusion gene formed. Two patients were found to have t(5;17), one with a diffuse nuclear NPM staining pattern and with NPM-RAR alpha and RAR alpha-NPM transcripts detected. In the other with an unbalanced der(5)t(5;17)(q13;q21) and a nucleolar NPM localization pattern, an NPM/RAR alpha rearrangement was excluded, and FISH revealed deletion of one RAR alpha allele. In the remaining 5 workshop patients, no evidence was found for a rearrangement of RAR alpha, indicating that in rare instances, alternative mechanisms could mediate the differentiation block that typifies this disease. This study highlights the importance of combining morphologic, cytogenetic, and molecular analyses for optimal management of APL patients and better understanding of the pathogenesis of the disease. (Blood. 2000;96:1297-1308)

We report on a novel chromosomal aberration, inv(8)(p11q24), in an M5 acute myeloid leukemia. We show by fluorescence in situ hybridization and Southern blot analyses that a t(8;16)(p11;p13) is masked by this inversion. The translocation targets the MOZ gene from the 8p11 and the CBP gene from the 16p13 chromosomal regions. The breakpoints occur in the MOZ region encoding the acidic domain and in the 5' end of the CBP gene. These results provide further evidence for the multiple contribution of both MOZ and CBP genes in acute leukemias. Genes Chromosomes Cancer 26:161-165, 1999.

Through two clinical studies, tumor cells were searched for in the bone biopsies and cytapherisis of patients suffering from inflammatory tumors and who had undergone intensive therapy and autografts (Pegase 2 program). In these studies we used immunocytochemical test with two monoclonal antibodies. The results have shown the presence of tumor cells in 14% of the patients (respectively 18%), with no correlation to the appearance of metastases after 4 years in the first study. Nevertheless, the presence of these tumor cells seems to be an important factor in the number of relapses. It seems important to develop research into tumor contamination especially in the selection of grafts over the next few years.

We report on the molecular characterization of two acute myeloid leukemias (AML), one AML-M1 (patient 1) and one AML-M2 (patient 2) with t(8;21)(p21;q22) and t(8;20)(q22;p13), respectively, at diagnosis. The locations of the breakpoints, 21q22 in patient 1 and 8q22 in patient 2, prompted us to search for a cryptic t(8;21)(q22;q22) and involvement of the AML1 and ETO genes. Dual-color fluorescence in situ hybridization (FISH) using whole chromosome painting probes for chromosomes 8, 20, and 21 confirmed the conventional cytogenetic karyotypes. However, dual-color FISH using appropriate ETO and AML1 probes disclosed an insertion of AML1 into 8q22 on the derivative chromosome 8 in patient 1 and of ETO into 21q22 on one chromosome 21 in patient 2, leading to AML1-ETO fusion signals. Both cases expressed an AML1-ETO transcript, shown by reverse transcriptase polymerase chain reaction and cDNA sequencing. Creation of functional AML1-ETO fusion genes in these two simple variant t(8;21) probably occurred through complex mechanisms, combining translocation and insertion of chromosomal segments.

Acute promyelocytic leukemia (APL) is characterized by the t(15;17) cytogenetic abnormality leading to the expression of two fusion genes, PML/RARA and RARA/PML, and by its sensitivity to all-trans retinoic acid (ATRA) differentiating treatment. Rare APL cases lacking the t(15;17) have been described. We have previously reported two cases presenting with submicroscopic insertions of RARA or PML into chromosome 15 or 17, respectively. These insertions lead to the formation of potentially functional, nonreciprocal, PML/RARA or RARA/PML fusion genes, providing the unique opportunity to investigate in a human noncell-line model the respective role of PML/RARA or RARA/PML in retinoid signaling. Here, we report the in vitro response to ATRA of these two cases as well as of a third case presenting with submicroscopic insertion (15;17) and expressing exclusively PML/RARA, by morphological, functional, and immunological assays. The two cases expressing PML/RARA presented with an immunostaining pattern typical of APL and a positive response to ATRA, whereas the APL case expressing only a RARA/PML fusion transcript exhibited an immunostaining pattern typical of non-APL cells, and was resistant to ATRA. Our results confirm that sensitivity to ATRA requires expression of PML/RARA and strongly correlates with immunostaining, and demonstrate that expression of RARA/PML alone is sufficient for a cytological APL phenotype, but does not confer sensitivity to ATRA.

FLT3/FLK2 is a receptor tyrosine kinase (RTK) which is thought to play an important role in early stages of hematopoiesis. Monoclonal antibodies (mAbs) against the extracellular domain of human FLT3 were generated to study the cell surface expression of this class III RTK on normal bone marrow cells and on leukemic blasts from patients with acute leukemias. Functional analysis of five mAbs (SF1 series) revealed that all of them can mimic to variable extents the activity of the FLT3 ligand (FL) upon receptor activation and modulation, while only one mAb weakly inhibited ligand binding. Using flow cytometry, we detected surface expression of FLT3 on cell lines of the myeloid (4/8) and B lymphoid (7/10) lineages. On normal human bone marrow cells, the expression of FLT3 is restricted, in agreement with a presumed function of this receptor at the level of the stem cells and early committed progenitors. Expression of FLT3 was found on a fraction of CD34-positive and CD34-negative cells. Three-color analysis further revealed that most of the CD34 FLT3+ cells coexpress CD117 (KIT) at a high level. Finally, FLT3 is expressed on leukemic blasts of 18/22 acute myeloid leukemias (AML) and 3/5 acute lymphoid leukemias (ALL) of the B lineage, providing a possible application in diagnosis and therapy of these diseases.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of a stem cell, involving myeloid, erythroid, megacaryocyte, lymphoid B-cells and "natural killer" cells. The hallmark of CML is the Philadelphia (Ph) chromosome which is a shortened chromosome 22 (22q-) resulting from a reciprocal translocation involving chromosome 9 and chromosome 22, designed t (9;22) (q34;q11). This translocation juxtaposes parts of two genes; ABL on chromosome 9 and BCR (breakpoint cluster region) on chromosome 22. Transcription of the BCR/ABL fusion gene results in an hybrid mRNA that is translated into a 210 kDa or 190 kDa protein, depending on the location of the breakpoint in the bcr region. This protein plays a key role in CML: its tyrosine-kinase activity, that differs from the normal ABL product, may be involved in leukemic cell growth. Nonetheless, the loss of the negative cell growth regulation by c-ABL, or BCR/ABL fusion protein interaction with other cellular genes (such as RAS or c-MYC) could also be involved in CML pathophysiology. A better understanding of the molecular mecanisms of CML could lead to specific treatment, such as tyrosine-kinase inhibitors, synthetic oligodeoxynucleotides, or site-specific DNA-binding proteins designed against BCR/ABL oncogenic fusion sequence.

The authors report two cases of acute myeloid leukemia with prevalent cutaneous lesions. The positivity of granulo-monocytic antibodies and the exclusive cutaneous site of the lesions drove them previously to the diagnosis of histiocytic sarcoma. These cases stress the problem of the immunological identification of cutaneous lymphomas of "histiocytic" type.

Patients with acute leukemia who relapse after intensive chemotherapy have a poor outcome with subsequent and even more aggressive chemotherapy. Results of allogeneic bone marrow transplantation have demonstrated the importance of the allogeneic effect in the curability of leukemias [1, 2]. Furthermore, T cell depletion from the graft has pointed out the critical importance of T cells in the mechanism of this so-called graft-versus-leukemia effect [3, 4]. These allogeneic cells represent an adoptive form of immunotherapy showing a possible control of leukemic cells by recombinant interleukin-2 (rIL2). However, previous clinical trials using in vivo immunotherapy with agents such as bacille Calmette-Guerin failed to demonstrate any impact of this approach on acute leukemia. This is probably due to the lack of specificity or to the relatively modest degree of immune stimulation obtained with such agents.

Patients undergoing immunotherapy with Interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed the profound neutrophil chemotactic deficiency induced by Interleukin-2 therapy. Peripheral blood cells exposed to Interleukin-2 in vitro secrete secondary cytokines. The release of tumor necrosis factor into the circulation after Interleukin-2 injection has been proposed as an important mechanism underlying cell function alterations. We tested chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients. Serums induced a defective chemotaxis of normal neutrophils similar to the one observed with neutrophils from Interleukin-2 treated patients. We have previously demonstrated a dose-dependent reversion of neutrophil chemotaxis after incubation with anti-Tumor Necrosis Factor-alpha antibody. Pentoxifylline is known for counteracting the inflammatory action of tumor necrosis factor. We tested its capability to reverse the chemotactic deficiency of neutrophils induced by treated patient serums. Pentoxifylline was added after incubation of normal cells with patient serum, and the directed chemotaxis was restored. Pentoxifylline may have a significant therapeutic potential for the prevention or treatment of complications related to inappropriately activated neutrophils.

The authors report 6 cases of histological transformation in peripheral T-cell lymphomas of low grade of malignancy. The transformation occurs in 75% of the cases, in extra-nodal sites and corresponds to a monomorphic of pleiomorphic large cell type. There is no discordance in the immunologic results between the two phases. The transformation seems to occur earlier than in B lymphomas, with a relative frequency of hematological manifestations and no therapeutic response.

Unusual gram positive bacteremia has been reported in non granulopenic patients receiving recombinant human interleukin-2 (IL-2) suggesting a beneficial effect of anti gram positive prophylaxis in such patients. We report here studies on granulocyte functions examined during the course of high dose IL-2 therapy (16 to 24 million IU/m2/days for 11 to 18 days) administered during a period of 35 days in 14 patients including 4 solid tumors, 5 chronic myeloid leukemias, 4 recipients of autologous bone marrow transplant (ABMT) and 1 recipient of syngeneic bone marrow transplant. Neutrophils functions were studied before IL-2 administration (d 0), after the first cycle (d 8) and after the third cycle (d 36). Nylon fiber adherence, superoxide production, random migration, phagocytosis, nitroblue tetrazolium reduction, lysozyme and elastase release were not impaired significantly throughout therapy. However N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP) stimulated chemotaxis of granulocytes, normal before therapy, was significantly impaired as early at d 8 and severely inhibited at d 36 (p less than 0.001). Three septicemia, one corynebacteria parvum septicemia and two gram-negative septicemia despite normal neutrophil counts and oxacillin or Penicillin G plus Pefloxacin prophylaxis, occurred among the 14 patients studied. Although neutrophil functions were not more depressed in transplanted patients than in the other non transplanted patients, special attention should be paid to such patients in whom delayed immune reconstitution could increase the risk of sepsis.

We report a case of granulocytic sarcoma of the bone with pleural involvement diagnosed upon cytologic analysis of the pleural fluid (centrifugation spots stained by May-Grunwald-Giemsa) and confirmed by more complex investigations, i.e., demonstration of granulomonocytic membrane antigens by immunohistochemical monoclonal antibody techniques on frozen sections of the tumor. This case draws attention to the value of cytologic studies in granulocytic sarcomas whose histologic features are suggestive of lymphoma.

A case of acute erythremia with a chromosomal translocation (8 ; 9) is presented. Response to chemotherapy was poor and the patient died 2 months after the diagnosis. The characteristics and nosological situation of this rare erythroid neoplasia are discussed.

Seven iridoids are isolated from Borreria verticillata root barks: daphylloside 1, asperuloside 2, feretoside 3, methyl desacetylasperulosidate 4, desacetylasperuloside 5, asperulosidic acid 6 and desacetylasperulosidic acid 7. Their structures result from spectroscopic analysis and are proved by chemical correlation.

Twenty-six patients (median age 33 years) with poor-risk malignancies were treated with high-dose combination chemotherapy associating BCNU-etoposide-cytosine arabinoside and melphalan (BEAM) followed by autologous bone marrow transplantation (ABMT). Twenty-one patients had malignant lymphomas, three, acute lymphoblastic leukemia (ALL), and two, malignant thymomas. Eleven patients (group 1) were not in complete remission (CR) at the time of BEAM, and fifteen patients (group 2) were in CR. Hematological recovery occurred in all patients. The duration of aplasia and the non-hematological toxicities were similar in both groups. Ten of the eleven patients (group 1) evaluable for response achieved CR and one achieved partial remission (PR). Five patients relapsed, and five are in continuous CR with a short follow-up (median 8 months). Among the fifteen patients in CR at the time of BEAM (group 2), four patients relapsed and ten patients are in unmaintained continuous CR with a median follow-up of 15 months (one patient died in CR). The disease-free survival is 53%, with 29% for patients receiving BEAM while in relapse (group 1) and 65% for patients receiving BEAM while in CR (group 2). These data indicate that BEAM followed by ABMT can produce a high antitumor response with an acceptable toxicity in patients with poor-risk malignancies.

Methotrexate (MTX) and vindesine (VDS) have both been found effective in the treatment of acute leukemia. With regard to their pharmacological effects at the cellular level they can reportedly interact. Administration of MTX at high dose levels has been suggested as both a curative and preventive treatment of blastic meningitis. The purpose of this work was to determine whether an injection of VDS leads to any change in MTX clearance and uptake in the cerebrospinal fluid (CSF). The plasma pharmacokinetic and CSF influx of MTX and VDS were assayed after high dose systemic MTX with an intravenous bolus of VDS administered in the treatment of acute lymphoblastic leukemia. The MTX concentration was determined by enzymatic assay and VDS by radio immunoassay. No interrelation between these drugs was found. MTX levels in the CSF were sufficient for therapeutic effectiveness but were not affected by intravenous VDS. Detectable amounts of VDS were observed in the CSF but were not altered by MTX.

Twenty-eight patients with malignant lymphoma were treated with high dose chemo or chemoradiotherapy and allogeneic or autologous bone marrow transplantation. They can be divided in two groups: Group 1: (19 pts) consisted in patients in relapse or in n complete remission (n greater than 2) (high risk patients); Group 2 (9 pts) consisted in patients in first or second complete remission at time of bone marrow graft (standard risk patients). Complete remission was achieved in 11/17 patients evaluable for response (65%). Duration of response is very different for two groups: in group 1, all patients relapsed within a median of 2 months (range: 1-12) and died within a median of 7 months (range: 2.5-15). In group 2, 7/9 are alive and well in unmaintained CCR in a median of greater than 18 months (range: greater than 15- greater than 36) (P less than 0.01). This experience shows the feasibility of this approach, the obvious antitumoral activity of these conditioning regimens and invited us to use such therapy at an earlier stage of the disease.

We report one case of T cell type lymphoma with multilobated nuclei, a distinct variant described by G. Pinkus. The soft palate and subcutaneous tissues were the successive localisations. Despite an aggressive chemotherapy with autologous bone marrow transplantation, a fatal course happened in 18 months. This entity is different from cutaneous lymphomas, mantle zone lymphomas of Waldron, Japanese T lymphomas and from the cases described recently by Weisenburger. The link between these different anatomo-clinical and histological varieties is their belonging to the T cell line.

The role played by T lymphocytes in myelopoiesis has been established in in vitro studies. Dysregulation of the lymphoid system results in quantitative and, more rarely, qualitative abnormalities of myelopoiesis. The authors report the clinical data of two cases of peripheral T cell lymphoma associated with an AREB type of dysmyelopoiesis. The fact that both conditions were diagnosed simultaneously and progressed in parallel is an indirect argument in favour of the regulation of myelopoiesis by the T lymphocytes.

Mediterranean visceral leishmaniasis is not only a children disease. We observed 12 adult cases since 1971. Clinical presentation usually associates anarchic fever and splenomegaly, with anaemia, leucopenia, increased sedimentation rate and hypergammaglobulinemia. We must think to kala-azar, specially after a stay in an endemic country (mediterranean area), ask for parasites on bone-marrow smears and more often immunological diagnosis. Spontaneously fatal, the disease is easily cured by antimony derivatives.

A total of 8% of chronic lymphocytic leukemias (CLL) occur in young people, before the fourth decade, and can be considered as a specific clinical form of CLL. We report 24 cases of young CLL treated since 1975. The clinical course has the same characteristics in young as in old people except for the high tumoral B stage which has a worse prognosis.

The authors report of a case of composite lymphoma, defined by the coexistence of two clearly different types of malignant lymphoma in a single lymph node or splenic site. A review of the literature led to the discovery of 20 cases of this type of lymphoma. The macroscopic and histological lesions are analysed.

In this report we rate a new, third-generation automated hematology system (Technicon Instruments H-1) that can furnish a full range of values, including erythrocyte parameters and a leukocyte differential count. Particular attention is focused on erythrocyte morphometric parameters, including measurement of cell size and hemoglobin content on a cell-by-cell basis. We assess the usefulness of new parameters derived from these measurements, such as mean corpuscular volume and red blood cell distribution width, which characterize cell size, and mean corpuscular hemoglobin concentration, and hemoglobin distribution width, which characterize cell hemoglobinization in evaluating normal and abnormal subjects. The value of these parameters in classifying anemias is assessed in our patient population that includes those with iron deficiency anemias and thalassemias, as well as other forms of anemia.