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Chronic B lymphocytosis with binucleated lymphocytes (LWBL) is a recently described entity. The lymphocytosis is stable over years and atypical binucleated lymphocytes are detected on peripheral blood smears. Further investigation has shown a predominance in females, a polyclonal increase in serum IgM and HLA-DR7 expression in most cases. In almost all cases cytogenetic studies with classical culture conditions have not shown any abnormality. We describe 7 patients with LWBL associated with an abnormal karyotype. An additional i(3q) was found in 6 cases. Premature chromosome condensation (PCC) was detected in all 7 cases. As both abnormalities are rarely present in other benign or malignant proliferations, we suggest a strong correlation between LWBL and i(3q) and/or PCC.

LWBL is characterized by persistent and stable lymphocytosis, seen in but not exclusively female patients, with binucleated lymphocytes evident on peripheral blood smears. There is a polyclonal increase of serum IgM and in all cases immunophenotyping revealed a polyclonal expansion of B-lymphocytes. Whether this syndrome represents a premalignant disease process or a true polyclonal lymphocytosis remains unsettled. The occasional reports of clonal Ig rearrangements in this disorder suggest that in a minority of cases the polyclonal expansion may be followed by the emergence of one predominant clone. The demonstration of a clinically, benign, clonal lymphoid population is well recognised in several T cell disorders such as in the syndrome of large granular lymphocytes expansion. The benign clinical course and the lack of biological evolution in the majority of cases suggest that the importance of recognition of this disorder lies in avoiding aggressive therapy in these cases. A careful follow-up of these patients is mandatory and prospective immunological and genetic studies performed at different stages of the disease may well clarify this issue, particularly since most patients were HLA-DR7 positive.

Human T lymphotropic virus type II (HTLV-II), originally isolated in 1982 from a patient with a "T hairy cell leukemia", has not yet been proven to be the causative agent of any specific hematological disease. In order to screen for such an event, and because HTLV-II has a preferential tropism for OKT8 (CD8) T cells (both in vivo and in vitro), we searched for the presence of HTLV-II in lymphoproliferative diseases (LP) of CD8+ T cells. We report a serological and/or molecular study of 169 patients with a T CD8 LP, including 76 patients with malignant or reactive T CD8 LP (34 lymphomas, 27 large granular leukemias, three prolymphocytic leukemias, one hairy cell leukemia, 11 reactive T CD8 LP) and 93 HIV-1+ patients with a T CD8 peripheral lymphocytosis ( > 1500/mm3) from a prospective HIV cohort involving 1264 individuals. In the first series, the 40 sera available were all HTLV-I/II negative, except a 67-year-old French Guyanan man, with a cutaneous large T CD8 cell lymphoma, HTLV-I+. Furthermore, the molecular analysis of the 69 available DNA samples by PCR failed to detect any proviral HTLV-I/II sequences, except for the HTLV-I+ patient. The serological study of the 93 HIV-1+ individuals with CD8 lymphocytosis, showed that three patients were HTLV-I+, but none was HTLV-II+. Thus, in contrast to HTLV-I, whose etiological role in adult T cell leukemia is now well established, there is neither epidemiological nor molecular evidence that prototypic HTLV-II may be etiologically associated specifically with any of the CD8+ T cell LP investigated in this report.

A prospective, randomized trial was initiated in adult acute lymphoblastic leukemia (ALL) to compare (1) disease-free survival (DFS) after allogeneic or autologous bone marrow transplantation (BMT) and (2) the relapse rate of patients treated with or without interleukin-2 (IL-2) after autologous BMT. A total of 135 previously untreated patients, aged under 55 years, received the Berlin-Frankfurt-Muster (BFM) induction regimen: 126 patients (93%), of which 120 were HLA-typed, achieved complete remission (CR). According to this genetic randomization, patients with (n = 43) or without an HLA-identical sibling (n = 77) were to receive allogeneic or autologous BMT, respectively. The 3-year post-CR probability of DFS was significantly higher in the HLA-identical sibling group than in the non-HLA-identical sibling group (68% v 26%; P < .001). Eligible patients were randomized to receive (n = 30) or not to receive (n = 30) IL-2 after autologous BMT: the 3-year post-BMT probability of continuous CR was similar in both groups (29% v 27%, respectively). We conclude that, in ALL, early allogeneic BMT after the BFM induction regimen is an effective consolidation treatment and that IL-2 does not decrease the high relapse rate observed after autologous BMT.

Since 1986, we have treated young patients with aggressive multiple myeloma (MM) by high-dose chemotherapy (HDC) and total body irradiation (TBI) followed with autologous blood stem cell transplantation (ABSCT). To evaluate this strategy: 1) We conducted a phase II trial that included 63 patients. Within a median follow-up of five years after transplantation, overall survival was 60% and median event-free survival was four years, and 2) In the early 1990s, we initiated a prospective trial where, after collection of chemotherapy-mobilized ABSC, patients under 55 years of age with newly diagnosed MM were randomly assigned either to HDC and TBI supported with ABSCT (high-dose therapy [HDT] arm) or to a conventional vincristine, melphalan, cyclophosphamide and prednisone (VMCP) regimen (VMCP arm). In the latter, HDT with ABSCT was performed as a rescue therapy, in case of primary resistance to VMCP or at relapse in responders. As of June 1994, 167 patients have been enrolled since a median time of 26 months. Fourteen (8%) could not be randomized. Among the randomized patients (n = 153), 30 deaths were observed, 13 in the HDT group and 17 in the VMCP group (p = 0.28, two-sided log rank test). Overall survival rates at two years were estimated at 78% for all 167 patients, at 82% in the HDT group and at 67% in the VMCP group. ABSC, provided they are collected early in the disease course, allow a great majority of myeloma patients to receive HDT.(ABSTRACT TRUNCATED AT 250 WORDS)

Karyotypic detection of chromosomal 16 abnormalities classically associated with AML M4Eo can be difficult. Characterization of the two genes involved in the inv(16)(p13q22), CBF beta and MYH11, has allowed the detection of fusion transcripts by reverse-transcriptase polymerase chain reaction (RT-PCR). We have analyzed CBF beta-MYH11 fusion transcripts by RT-PCR in myelomonocytic leukemias, with or without eosinophilia, to determine whether their presence correlates with morphology. Fifty-three cases (11 AML M4Eo; 1 AML M4 with atypical abnormal eosinophils (AML M4 "Eo"); 29 AML M4; 8 AML M5; 3 CMML; and 1 AML M2 with eosinophilia) were analyzed. All 11 typical AML M4Eo were CBF beta-MYH11 positive. The single case of AML M4 with distinctive eosinophil abnormalities was negative by karyotype, RT-PCR and fluorescent in situ hybridization (FISH). Three of 29 (10%) AML M4 without abnormal eosinophils were CBF beta-MYH11 positive, 1 of which did not show any apparent chromosome 16 abnormalities by classical metaphase analysis (2 not tested). Both cases tested also showed MYH11 genomic rearrangement. None of the other leukemias were RT-PCR positive. Follow-up of three patient showed residual positivity in apparent complete remission. These data show that CBF beta-MYH11 fusion transcripts occur not only in the vast majority of typical AML M4Eo, but also in approximately 10% of AML M4 without eosinophilic abnormalities, a much higher incidence than the sporadic reports of chromosome 16 abnormalities in AML M4 would suggest. Taken together with the detection of CBF beta-MYH11 transcripts in the absence of apparent chromosome 16 abnormalities by classical banding techniques, these data show that additional screening by either RT-PCR or FISH should be performed in all AML M4, regardless of morphologic features, to allow accurate evaluation of the prognostic importance of this fusion transcript.

The t(1;19)(q23;p13) translocation occurs commonly in B-lineage ALL. Previous reports have demonstrated a predominance of cases with expression of cytoplasmic Ig mu (C mu+), and FAB L1/L2 phenotype, a poor prognosis and expression of a fusion transcript involving the E2A and PBX1 genes in C mu+ but not in C mu- cases. Of 38 patients with karyotypically proven t(1;19) (q23;p13) leukaemias, we extensively analysed 18 patients with acute leukaemia including 16 B-lineage ALLs, one T-ALL and one AML M4. The AML was associated with a classic E2A-PBX1 fusion transcript and may represent the human counterpart of the AMLs induced by E2A-PBX1 retroviral infection of murine marrow progenitors. The T-ALL was E2A-PBX1 negative and neither the E2A nor the LYL-1 genes, both situated at chromosome 19 p13, were rearranged. Of the 16 B-lineage ALLs, four had cytological features resembling an 'L3-like' phenotype classically associated with Burkitt's lymphoma, two at diagnosis and relapse and two exclusively at relapse. E2A-PBX1 fusion transcripts were detected by RT-PCR in all 13 C mu+ patients and in 2/3 C mu- cases. The 'L3-like' phenotype did not correlate with a particular stage of maturation arrest (one sIg+, one C mu+, one C mu-) or type of E2A-PBX1 transcript, but was associated in all cases with a trisomy 8. Translocation, rearrangement, amplification or over-expression of the c-myc gene was not observed in these cases, demonstrating that the apparent association with trisomy 8 is not due to deregulation of this gene. We therefore show that the E2A-PBX1 transcript, although occurring predominantly in C mu+ pre-B ALL, also occurs in C mu- early pre-B ALL, sIg+ B-ALL and even in AML. These results suggest that the stage of maturation arrest, and indirectly the prognosis, are not solely due to the type of fusion transcript associated with the t(1;19).

Introduction: T cell prolymphocytic leukemia (T PLL) is a rare variant of mature lympho-proliferative disorder. The main physical sign is a gross splenic enlargement contrasting with no enlargement of lymph nodes. Skin involvement is found in 30 p. 100 cases. Twenty-one cases of cutaneous lesions of PLL have been reported, mainly with T PLL, only 2 cases of B PLL: Clinical lesions are polymorphous; histology shows a dermal prolymphocytic infiltrate. The main cytogenetic abnormalities are: translocation (14; 14) (q11; q32), inversion of chromosome 14 (q11; q32), isochromosome 8q., Case Report: We report a case of an 87-year-old patient presenting a T cell prolymphocytic leukemia CD4+ with specific papular lesions of the back. Electron microscopy showed typical prolymphocytes and cytogenetic studies showed a tendency to polyploidy, with the lost of chromosome 14, translocation 8-22 and inversion of chromosome 13. After 12 months of treatment with a combination of chloraminophen and prednisone the patient was in partial remission and the cutaneous lesions disappeared., Discussion: This case is rare and the patient has an unusual long survival (mean survival is 7 months). Contrary to the other hematologic disorders, cutaneous involvement does not change the prognosis of T PLL:

Double hemibody irradiation (DHBI) is an alternative treatment of stage III multiple myeloma (MM) in patients aged over 55 years. Toxic side-effects such as myelosuppression are a severe limiting factor to its use. We performed DHBI associated with human recombinant granulocyte-macrophage colony stimulating factor (hrGM-CSF) as support therapy in 10 patients with stage III MM to improve the tolerance to this treatment. Ten patients received subcutaneously 5 micrograms/kg/d of hrGM-CSF during 2 weeks after each course of hemibody irradiation. All these patients had stage III MM: eight previously received chemotherapy, six of them were regarded as patients with refractory MM and two with relapse. Two patients received DHBI as first-line treatment. hrGM-CSF increased safety and tolerance of DHBI. GM-CSF support reduced the mean time between upper body irradiation (UBI) and lower body irradiation (LBI): 41 v 108 d in a cohort of 32 patients previously treated without growth factor support. Overall there was no lethal infection with hrGM-CSF or granulocytopenia (5.0 x 10(9)/l v 0.4 x 10(9)/l at day 15 in patients without growth factor). hrGM-CSF also reduced stomatitis grading and thrombocytopenia (90 x 10(9)/l v 45 x 10(9)/l at day 15). Furthermore, hrGM-CSF increased blood colony forming unit-granulocyte macrophage (CFU-GM) and was well tolerated in all but one patient. hrGM-CSF reduces toxic side-effects of DHBI, thus providing an effective treatment in patients with advanced and resistant MM.

Purpose: To confirm and extend encouraging preliminary results of timed sequential chemotherapy (TSC) in patients with previously treated acute myelogenous leukemia (AML)., Patients and Methods: We report the results of the regimen of mitoxantrone on days 1 to 3, etoposide on days 8 to 10, and cytarabine on days 1 to 3 and 8 to 10 (EMA) in 133 patients, with a median follow-up of 40 months., Results: Sixty percent of patients, with a 95% confidence interval (CI) ranging from 51% to 68%, achieved complete remission (CR), including 44% (CI, 32% to 57%) of refractory patients and 76% (CI, 64% to 86%) of late first-relapse patients (P = .0002). Twenty-nine percent of patients did not respond to therapy, and 11% died from toxicity. Median duration of neutropenia and thrombocytopenia was 31 days and 29 days, respectively. Severe nonhematologic toxicity included sepsis in 54% of patients and mucositis in 23%. Postinduction therapy included a second course of EMA in 27 patients, maintenance in 10, autologous bone marrow transplantation (BMT) in 12, and allogeneic BMT in 13. Median survival of patients who did not have transplantation performed is 7 months, with 11% (CI, 4% to 18%) survival at 5 years. Median disease-free survival (DFS) is 8 months with 20% (CI, 8% to 32%) DFS at 5 years. Twenty-eight percent (CI, 15% to 44%) of nontransplanted patients who achieved CR had an inversion of CR duration. Previous refractoriness was the main factor associated with poor prognosis for CR achievement, DFS, and survival., Conclusion: These results confirm initial reports on TSC and show that approximately 20% of patients with first relapse after therapy can enjoy prolonged DFS using chemotherapy only.

We describe a new and original therapy with total body irradiation in two separate 4 gy single courses (double hemibody irradiation) combined with GM-CSF support, 5ug/day on days 1-15 after each hemibody irradiation, for refractory patients with B-chronic lymphocytic leukemia (CLL). A complete response was observed in a patient with a B-CLL resistant to CAP and FAMP therapy. Overall tolerance was good. The major points of interest in this technique are the combination of the antitumor effect of irradiation, limited bone marrow toxicity and a potential specific anti-leukemia effect of GM-CSF.

Persistent lymphocytosis is usually associated with a malignant lymphoproliferative disease (MLPD). We report six female patients presenting a chronic, moderate lymphocytosis of 2-16 years duration with atypical binucleated lymphocytes on peripheral blood smears. Further investigation showed a polyclonal increase in serum IgM and HLA-DR7 phenotype in all patients. The B cells were polyclonal because Southern hybridization of DNA and polymerase chain reaction failed to demonstrate a clonal rearrangement of immunoglobulin heavy chain genes. Peripheral blood examination showed binucleated lymphocytes in a family member of two of the cases; taken together with the association with HLA-DR7 these data suggest a genetic predisposition. The identification of this benign syndrome is important in order to prevent its misdiagnosis as a MLPD.

The adrenal gland is affected in about 25% of patients with diffuse lymphoma. Conversely, primary lymphoma is a rare cause of non-secreting adrenal tumour. We observed a recent case with exclusive right adrenal localization. An 84-year-old woman was hospitalized for asthenia, anorexia and a 3-kg weight loss. The past history included coronary heart disease. Physical examination was normal and the hemogram revealed pancytopenia. No lymphomatous infiltration was seen on the myelogram or the bone marrow biopsy. Echography of the abdomen showed a well-limited 10 cm mass above the right adrenal gland, distinct from the liver; the left gland had a normal aspect. Hormone assays were within normal limits. The right adrenal gland was removed surgically and histology revealed diffuse proliferation of medium to large sized lymphoid cells invading the entire gland. Immunohistochemistry suggested lymphoid B origin. No curative treatment was begun, but 2 months after surgery local invasion required polychemotherapy. The patient died of septic shock 5 days later. Serum cortisol measured during the septic shock eliminated adrenal gland failure. Malignant primitive non-Hodgkinien lymphomas are extremely rare and usually discovered incidentally. The tumour is always large and sometimes accompanied by adrenal insufficiency when the lesion is bilateral. In spite of suggestive imagery the diagnosis is based on the pathology examination. The lesion is usually a high-grade malignant phenotype B lymphoma. Treatment relies on chemotherapy but is disappointing.

We retrospectively analysed the results of interferon alpha-2 (IFN) treatment in 93 patients with hairy-cell leukaemia, of which 31 had previously undergone splenectomy. Induction treatment (3 x 10(6) U three times weekly for 12 months) was completed in 84 cases (90%). Peripheral hematological response was observed in 76 patients. Two patients had persistent splenomegaly, and response was observed in both cases after splenectomy. Five additional patients were responsive after 18-24 months of induction treatment and 1 was unresponsive. Of 28 patients on maintenance treatment (1 x 10(6) U 3 x per week), no patient relapsed after a median follow-up of 30 months. The toxicity level was acceptable and IFN resistance was not observed. On the other hand, of 56 patients without maintenance treatment, 37 relapsed at a median of 19 months. Thirty of 32 evaluable patients remained responsive to a second course of IFN. Of 19 patients without relapse, 11 had undergone splenectomy compared to 0/37 patients who relapsed (p < 0.001). In conclusion, the study shows the following, (1) IFN, provides excellent palliation without major toxic side effects; (2) long term maintenance was well tolerated and prevented peripheral haematological relapse; (3) lack of maintenance treatment was associated with peripheral haematological relapse requiring a second treatment; and (4) certain previously splenectomized patients may not require maintenance treatment. These long term results must be compared with the effectiveness and toxicity of new drugs, such as pentostatin and 2-chloro-deoxy-adenosine.

Among patients included in the multicentric trial ALL87, 95 patients were randomly allocated to purged ABMT arm for post-remission therapy. Immunological phenotyping performed in patients at diagnosis allowed to assigned 51 patients (54%) to the B lineage and 34 patients (36%) to the T lineage. Only 64 patients (67%) actually received ABMT mainly because of early relapses. Fifty-two patients were depleted according to the protocol: 25 B-ALL were depleted with CD10+CD19 mAbs, 19 T-ALL with CD2+CD5+CD7 mAbs and 8 patients received an Asta-Z purged BMT. Among the 12 remaining patients, 4 received Asta-Z purged BMT and 8 an unpurged one. Using an intention to treat analysis, overall survival and event free survival were similar to results observed in chemotherapy group. This study emphasizes the importance of a precise phenotyping at ALL diagnosis which allows specific immunologic bone marrow purging for ABMT.

Septicemia due to Clostridium perfringens during the course of acute leukemia is rare and often lethal particularly in childhood. Antibiotherapy is necessary but polymorphonuclear activity recovery is helpful. This can be done through transfusion or administration of colony stimulating factors. Here is a new case of such a septicemia in a 12 year-old female treated for acute lymphoblastic leukemia. Of particular interest is the favourable outcome despite a high risk situation.

Diarrhea in marrow transplant recipients is a frequent complication attributable to non-infectious events such as acute GVHD or infectious events such as viral gastroenteritis. Rotavirus and enteric adenovirus are the most frequent viral pathogens. To determine the frequency of these infections, we prospectively examined the stool specimens of 94 patients who underwent autologous BMT (34 cases) or allogeneic BMT (60 cases). Stool specimens were examined from patients twice weekly. Nineteen of the 94 patients were infected with viral pathogens. This study showed: (1) an incidence of viral gastroenteritis identical in autologous and allogeneic BMT (20%), (2) a persistent risk despite treatment in laminar air flow rooms, (3) a significant association with severe acute GVHD, and (4) a significant risk of multiple viral infections in autologous BMT recipients. Rotavirus and adenovirus are a cause of enteritis involvement in patients undergoing BMT and they may be underdiagnosed and confused with GVHD. Screening of stool specimens after BMT should be directed to prevention and treatment of these viral infections to decrease the morbidity and mortality associated with BMT.

Apparition of new tools in the therapy of multiple (MM) strengthens the need for valuable prognostic categorization of each patient in order to propose the most adequate treatment. Prognostic factors in MM can be divided in four groups. The first, including beta 2 microglobulin (beta 2m), hemopoiesis impairment, osteolytic lesions, calcemia and albuminemia, reflects the tumor mass. The second: type of monoclonal component, labeling index (LI), C-reactive protein (CRP), cytologic, histologic and immunophenotypic aspects of plasmocytes, renal biology, ADN and ARN, contents of malignant cells, LDH levels, activation of ras oncogene represents the intrinsic malignancy of the clone. The third illustrates the type of response to chemotherapy. Finally, the last group characterizes the host and his reactivity against the disease. Thus, the referential prognostic classification of Durie and Salmon representing only the tumor burden, seems to be now insufficient. New classifications including CRP, beta 2m and LI as more discriminant parameters are currently proposed.

Severe acute GVHD remains the main complication in unrelated donor BMT (UD-BMT). The previous encouraging reports on the use of anti-IL-2 receptor monoclonal Ab (33B31) for GVHD prophylaxis in genoidentical BMT led us to add this Ab to the standard GVHD prophylaxis regimen (MTX plus CsA). Sixty-four consecutive patients received 33B31, 20 mg on days 1 and 2, then 10 mg per day from day 3 to day 28 in association with CsA and MTX. They were compared with a historical control group of 89 patients who received conventional GVHD prophylaxis. The 33B31 was well tolerated. We did not find any statistical difference in terms of incidence and time of onset of severe GVHD, occurrence of chronic GVHD, engraftment, relapse or survival among the two groups. Immunization occurred but did not influence serum levels of 33B31. No correlation was found between the severity of GVHD and serum Ab levels. We conclude that other approaches for reducing acute GVHD should be developed to improve UD-BMT results.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), given intravenously 5 micrograms/kg per day, was administered on days 4-8 of timed-sequential chemotherapy (TSC) with mitoxantrone, 12 mg/m2 per day on days 1-3, etoposide, 200 mg/m2 per day on days 8-10 and cytarabine, 500 mg/m2 per day on days 1-3 and 8-10, in 22 patients aged < 60 years with refractory acute myelogenous leukemia in an attempt to increase recruitment of leukemic cells in S phase before the second sequence of TSC. Thirty-eight patients treated with TSC without GM-CSF in a previous trial served as historical controls. In GM-CSF-treated patients, median duration of neutropenia < 0.5 x 10(9)/1 was 33 days and of platelet transfusion requirement 30 days, without any increase by comparison with controls. WHO grade 3 or more extra-hematologic toxicity included sepsis in 60% of patients, vomiting in 30%, diarrhea in 15%, hyper-bilirubinemia in 15%, and mucositis in 10%, without any difference with controls. Among 20 evaluable patients six individuals (30%), with a 95% confidence interval (CI) ranging from 12-54% achieved complete remission, 11 (55%, CI 31-77%) did not respond to therapy and three (15%, CI 3-38%) died from infection. There was no demonstrable in vivo proliferation of leukemic cells during the 5 days of administration of GM-CSF. The average percentage of bone marrow cells in S phase in five patients was 4.0 +/- 2.8 on day 4 and 7.0 +/- 7.2 on day 8 (p = NS). In this cohort of patients refractory to cytarabine, addition of GM-CSF did not increase efficacy of TSC by comparison with historical controls.

Acral erythema (AE) is a painful, erythematous bullous eruption of the palms and soles which is chemotherapy-induced. To the numerous chemotherapies which induce AE we must add, perhaps, a new drug, Vépéside. AE is followed by graft-versus-host-disease in all patients receiving bone marrow transplantation. AE and early GVH disease being very similar, we discuss the differential diagnosis which can be very difficult.

A female patient simultaneously developed hematologic evidence of hairy cell leukemia and marked but short-lived inflammatory involvement of a number of joints. Both these groups of symptoms resolved simultaneously and rapidly under alpha-2 interferon therapy. This course suggests that the arthritis was a rheumatologic manifestation of the hematologic disease. The concomitant occurrence in this patient of arthritis, splenomegaly and leukopenia was suggestive of Felty syndrome: these two conditions need to be differentiated.

The occurrence of cytomegalovirus (CMV) viremia after transplantation is predictive of visceral lesions. Three-hundred and sixty blood samples were collected from 21 transplant recipients and examined. Direct CMV antigen detection was positive in 41 samples (11.4 percent), rapid viral isolation in 24 samples (6.7 percent) and conventional cell culture in 9 cases (2.5 percent). Direct detection of CMV antigen in blood leucocytes is as specific as, and more sensitive and rapid than isolation in culture. In 50 percent of secondary infections the antigenaemia assay and serology were equally sensitive, and antigenemia appeared earlier in 2 primary infections.

The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage I must not be treated. The Melphalan Prednisone regimen is the reference for induction therapy because polychemotherapies are generally not superior. At this phase, the addition of Interferon alpha seems to be interesting. This drug has an important role during the steady-state phase. VAD represents the most efficient chemotherapy. Body hemi-irradiation is also useful. The analgesic effect and the decrease in the tumoral mass are the striking effects of this treatment. In young patients, high dose chemotherapy with bone marrow transplantation is proposed. Verapamil and anti-IL6 antibodies are currently being evaluated. Symptomatic treatment is essential in this non curable disease.

While investigating the cause of mild polycythemia in a young man, a testicular seminoma was discovered with unusual and tumor-dependent features: an absolute polycythemia with high plasma erythropoietin (EPO) levels, an overproduction of estradiol and testosterone, and a dramatic Leydig cell hyperplasia surrounding the tumor tissue. The authors attempted to gain insight into the relationship between this testicular tumor and the hormonal overproduction, i.e., of EPO, estradiol, and testosterone. Their results favored the conclusion that the high EPO levels and the polycythemia were an indirect effect secondary to the steroid overproduction rather than a direct EPO-producing activity. Moreover, the steroid overproduction by the testis could be caused by a paracrine mechanism through human chorionic gonadotropin activity on the Leydig cells.

Two cases of acute megakaryoblastic leukemia in a 4 month-old and a 13 year-old girl are described. In the first case who presented with a large hepatomegaly and portal fibrosis, the diagnosis was made from the surface phenotyping of megakaryoblasts; a trisomy 13, 14 and 19 and an extra chromosome X were present in the bone marrow. An electron microscopy study of megakaryoblasts was necessary to identify the second case. Both children died shortly after treatment (cytosine-arabinoside at low dosage in the first case and polychemotherapy in the second). The 51 other cases reported in the literature are reviewed.

A case of Sweet syndrome in a patient with an acute myelomonocytic leukemia is reported. It is an unusual case simulating a facial erysipela. This case illustrates the difficulty in differentiating infection from Sweet syndrome in an immunocompromised patient. The negative cultures, ineffective antibiotics, and histopathologic examination results allowed the onset of corticosteroid therapy. The phagocytic function of the neutrophils studied by chemoluminescence was normal in the patient. The physiopathology of Sweet syndrome is discussed, in particular the role of cytokines in the accumulation of granulocytes.

Thirty-nine patients with relapsed acute lymphoblastic leukemia (ALL) and four with primarily refractory ALL were treated with a regimen that included cytarabine 1 gm/m2 (2-hour infusion) twice daily days 1 to 5, mitoxantrone 12mg/m2 daily days 1 to 5, prednisone 0.5 mg/kg daily days 1 to 5, and etoposide 200 mg/m2/day daily days 6 to 8. Of the 43 patients, 30 achieved a complete remission (CR), 28 out of the 39 relapsed patients and two among the four with refractory disease. Five patients died in aplasia. Eight patients were nonresponders. Nonhematologic side effects consisted predominantly of nausea, vomiting, and mucositis. One patient had transient cerebellar dysfunction. Recovery of blood counts occurred at a median of 24 days. The median time to CR was 38 days. As this regimen is highly effective in relapsed or refractory ALL, its use during earlier stage of the disease is warranted.

The prognosis of adults with Burkitt's lymphoma is very poor and depends on initial CNS and/or bone marrow involvement. We report results in nine adult patients with CNS (n = 9) and/or bone marrow involvement (n = 7) treated in first complete remission (CR) with allogeneic bone marrow transplantation (BMT). CNS treatment before the conditioning regimen consisted of cranial irradiation at 15 Gy (n = 8) and intrathecal chemotherapy (n = 9). The conditioning regimen included cyclophosphamide and total body irradiation (TBI) in a single dose. No postgraft CNS prophylaxis was administered. At the present time, seven patients are alive and disease-free at 18, 23, 44, 47, 54, 54, and 59 months. Two patients died at 14 and 7 months from transfusion-related acquired immune deficiency syndrome and bacterial septicemia and were disease-free at the time of their death. These preliminary results should encourage the use of BMT. A prospective randomized trial is warranted to further specify and investigate the advantages of allogeneic BMT versus conventional chemotherapy.

Selective cardiac involvement by a malignant non-Hodgkin's lymphoma (primary lymphoma of the heart) is extremely rare. Cardiac lesions occurring in the course of a malignant non-Hodgkin's lymphoma (secondary lymphoma of the heart) are found at autopsy in about 10 per cent of the cases. Secondary lymphoma of the heart may involve all cardiac structures, but lesions of the right heart, and particularly the right atrium, are predominant. Clinical manifestations are usually non-specific and appear at a late stage, reflecting diffuse involvement. When the malignant non-Hodgkin's lymphoma is known, systematic two-dimensional echocardiography should easily detect the lymphomatous cardiac infiltration, irrespective of the presence or absence of symptoms. When the malignant non-Hodgkin's lymphoma is unknown, only histology can show that the heart tumour is a lymphoma, evaluate its extension and confirm that it is limited to the cardiac walls, provided the disease is treated at an early stage, prolonged complete remissions are observed after chemotherapy and/or radiotherapy.