Biomedical subjects

B Ramot

Publications and source records attributed to B Ramot.

At least 19 recordsLinked to original sources

PubMed2000

Expression of wild-type p53 and Bcl-2 family genes oscillates with recurrent remission and relapse in an unusual case of low-grade lymphoma.

Downregulation of apoptosis has been proposed as a mechanism of clonal expansion in low-grade B cell neoplasms. We have previously described an unusual case of CD5+ B cell lymphoma characterized by cycles of leukemic phase alternating with spontaneous remission. In the present study, we examined the involvement of apoptosis-related proteins in the progression of this cyclic lymphoma ex vivo. During the leukemic phases, the clonal cells were activated blasts expressing elevated levels of wild-type (wt) p53, Bcl-2, Bcl-x(L), and Bax, while Bak expression increased during the decline of lymphocytosis. Bax heterodimerized with Bcl-2 but not with Bcl-x(L). The anti-apoptotic Bcl-2/Bax heterodimers peaked during early leukemic phases and declined during regression. The elevation in Bcl-2, Bcl-x(L) and Bax expression during early leukemic phases seems to result from cell activation since a similar increase was induced by activating the remission phase leukemic cells in culture. The data suggest that wt p53, Bcl-x(L), and Bcl-2/Bax heterodimers support the accumulation of activated leukemic cells during the leukemic phases, while Bax and Bak may be involved in their decline during regression.

Acute Disease↗

PubMed2000

Neoplastic cell activation and proliferative response to CD40-ligand characterize recurrent leukemic bouts in an unusual case of low grade lymphoma.

Spontaneous fluctuations in activity of low-grade B cell lymphomas are common but not understood. An explanation may be offered by studying an atypical SLL/CLL case characterized by recurrent cycles of leukemic phase alternating with spontaneous remission (1). During remissions, residual IgMkappa+ leukemic cells exhibited resting phenotype, low proliferative response to CD4O-ligand and delayed apoptosis. In contrast, the acute phase counterparts were phenotypically activated, underwent rapid apoptosis in culture and proliferated extensively in response to membrane-anchored CD40-ligand. Transient bursts of serum TNFalpha and IL-10 preceded the acute phases, which were characterized by the co-existence of CD40-ligand+ T lymphocytes and lymphoma cells in the bone marrow. Based on ex-vivo and in-vitro data, we suggest that changes in the lymphoma milieu affect the neoplastic cell activation status, rate of proliferation in response to activated T cells and rate of apoptosis. These responses may underlie both the induction and spontaneous regression of the acute phases in this unique lymphoma. Our findings raise the possibility that part of this mechanism may have evolved during transformation of indolent common CLL to its more aggressive form.

Apoptosis↗

PubMed1999

Familial aggregation of nonhematological malignancies in relatives of patients with hematological neoplasms.

Familial aggregation of nonhematological malignant disorders (NHMD) was compared in 189 families of patients with hematological neoplasms (HN) with a control group of 36 families of patients with benign hematological disorders and a second group of 33 families of patients with diabetes mellitus. A self-administered questionnaire was used requesting from each family a full list of first- and second-degree relatives, their vital status, current age or age at death, and a list of their chronic diseases, including all malignant disorders. There was no evidence of a significantly increased tendency for developing NHMD among relatives of patients with HN as compared to controls (adjusted odds ratio of 0.88; 95% confidence interval 0.61-1.27). Moreover, in the HN group, no significant difference in the frequency of NHMD was found between the families with and without familial aggregation of HN. Based on the present analysis and our previous observations on familial aggregation of HN, we conclude that the increased aggregation of malignant disorders among relatives of patients with HN is unique to the hematopoietic system and might result from a genetic predisposition to HN in these families.

Adolescent↗

PubMed1995

[Long-term follow-up in polycythemia vera].

67 patients with polycythemia vera, diagnosed and treated between 1963-1990, were analyzed retrospectively. The mean follow-up was 7.4 +/- 5.1 years and median actuarial overall survival 23.6 years. 50% were treated with a single chemotherapeutic agent, and 46% with combinations of agents. In only 4% was phlebotomy the sole treatment. There were hematological complications in 18%, thromboses in 18%, and bleeding in 21%.

Combined Modality Therapy↗

PubMed1995

Postremission therapy with two different dose regimens of cytarabine in adults with acute myelogenous leukemia.

Sixty-seven out of 105 (64%) adults with de novo acute myelogenous leukemia (AML), achieving complete remission after induction chemotherapy, entered two successive postremission treatment protocols. Between 1987 and 1989, 35 patients received an intermediate dose of cytarabine (IDAC) along with other drugs. Between 1990 and 1993, 32 patients received high dose cytarabine (HIDAC) with similar other drugs. Patients treated with IDAC had a median survival of 13.8 months (95% CI 11.2-23.1 months) and a 2 year survival of 34.3 +/- 8.0%. Patients receiving HIDAC had a median survival of 35.5 months (95% CI, lower limit 29.8 months) and a 2 year survival of 71.6 +/- 9.4% (P < 0.002). The 2 year actuarial leukemia-free survival (LFS) was 17.8 +/- 6.6% in the IDAC group and 67.3 +/- 10.0% months in the HIDAC group (P = 0.004). The HIDAC group had a significant 2 year survival advantage over the IDAC group only in patients younger than 45 years. The 2 year survival in the first group was 83.3 +/- 10.8% versus 23.5 +/- 10.3% in the IDAC group (P = 0.0001). In patients older than 45 years, no significant differences in 2 year survival was noticed (52.9 +/- 15.78 versus 44.4 +/- 11.7, P = 0.8). Censoring the 21 patients who underwent bone marrow transplantation (BMT) at BMT did not change significantly the survival analysis of the patients in each group. This study is consistent with previous reports favoring HIDAC intensification in the postremission treatment of young patients with AML.

Actuarial Analysis↗

PubMed1995

Preferred usage of specific immunoglobulin gene segments in chronic lymphocytic leukaemia cells of three HLA-identical sisters.

We report three family members, including a set of identical twins, who developed CD5 positive B-CLL. The patients are female Ashkenazi Jews sharing an identical HLA phenotype. Two of the HLA loci (B35 and Cw4) were common with those already described as being shared by Ashkenazi Jews with an increased incidence of CLL. The rearranged immunoglobulin genes of the malignant cells of all three patients were found to express genetically related VH regions belonging to the VH3 subgroup, and chromosomal studies suggest a process of clonal evolution in one of the twins.

Aged↗

PubMed1995

A controlled trial of tranexamic acid therapy for the reduction of bleeding during treatment of acute myeloid leukemia.

In order to determine the efficacy of the antifibrinolytic agent tranexamic acid (TA) in reducing bleeding and platelet transfusions during the treatment of acute myeloid leukemia (AML), we conducted a randomized placebo-controlled double-blind study. Patients with AML undergoing induction or postremission consolidation chemotherapy were randomized into TA or placebo groups. Patients were not given platelet transfusions prophylactically but only when bleeding occurred. The severity of any bleeding event was scored. Thirty eight patients were randomized during induction. There were no significant differences between the two groups in the number of bleeding events and their severity or in the number of platelet transfusions given. Eighteen patients were studied during consolidation. In contrast, to the induction period, during consolidation there was a significantly less severe bleeding tendency in the TA group resulting in a lower platelet transfusion requirement [3.7 +/- 4.1 vs. 9.3 +/- 3.3 platelet units (p < .05)]. TA was well tolerated and no side effects were seen and no specific thromboembolic events were noticed. We conclude that giving TA during the thrombocytopenic period of AML patients undergoing consolidation chemotherapy is beneficial and safely reduces platelet transfusions.

Acute Disease↗

PubMed1994

The cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, and procarbazine (COPBLAM-I) regimen for intermediate-grade non-Hodgkin's lymphoma. Long term follow-up in 51 patients.

BACKGROUND: Cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, and procarbazine (COPBLAM-I) is a second generation combination chemotherapy for intermediate-grade non-Hodgkin's lymphoma (NHL). Since the first report by Laurence et al. in 1982, only a few series were reported on the long term results of this regimen. METHODS: In this prospective study, the clinical courses of 51 patients with intermediate-grade NHL (F, G, or H according to the International Working Formulation grading criteria) with a median age of 65 years (range, 55-81), who were diagnosed between 1983 and 1992, are reported. Eligibility criteria included at least one full cycle of the regimen and no previous chemotherapy. RESULTS: A mean of seven cycles (range, two to nine) with two escalations (range, zero to six) was administered. In a median follow-up of 2.4 years (range, 0.5-10), 33 patients (65%) experienced complete remission. The projected 3-year overall survival (OS) and progression free survival rates (PFS) were 58% and 77%, respectively, and the projected 5-year OS and PFS were 52% and 72%, respectively. In only 2 patients (4%) were treatment-related deaths observed, whereas nonfatal complications were more common. Patients in the low risk group, according to the international NHL prognostic index, had the best outcome. The mean percentage of projected dose intensity (DI) was 95% (range, 77-109), whereas no difference in DI was found between patients younger or older than 65 years. CONCLUSIONS: In a single center, COPBLAM-I combination chemotherapy was safe and effective for patients older than 55 years with intermediate-grade NHL.

Aged↗

PubMed1994

CD10+ cell population in the bone marrow of patients with advanced neuroblastoma.

Immunocytologic analyses of bone marrow can provide clinically useful prognostic information in neuroblastoma. While analyzing the bone marrow with a panel of monoclonal antibodies, which detect neuroblasts and other defining B-, T-, and myloid lineage, we identified two infants with stage IV-S neuroblastoma whose bone marrow contained a large population of common acute lymphoblastic leukemia (ALL)-like cells. This population expressed HLA-DR, CD19(B1), CD10(CALLA), and occasionally CD20(B1). Since 1988, 17 additional patients with advanced neuroblastoma (IV-S, III, and IV) were studied by us. In 10 of the 19 patients, the bone marrow revealed an expanded CD10 population (20-70%). It appears that this group of patients has a better prognosis. Out of 9 patients who did not have an expanded CD10 population, 8 died within 9 months from diagnosis, whereas out of 10 patients with an expanded CD10 population only one died and the others are alive, 6-30 months from diagnosis (P < 0.001). An expanded CD10 population in the bone marrow of disseminated neuroblastoma patients may therefore serve as a prognostic factor. Apart from the prognostic value of this particular population in the single patient, its presence may shed light on the interrelationship between the immune system and the neuroendocrine compartment.

Adolescent↗

PubMed1994

Familial aggregation of haematological neoplasms: a controlled study.

Advances in molecular biology techniques suggest that many haematological neoplasms originate from a transformation process at the level of the haemopoietic pluripotential stem cell. While familial aggregation has been reported for many haematological neoplasms, most studies were uncontrolled and examined the presence of the same haematological neoplasm as the index case. We assessed the familial aggregation of all haematological neoplasms in 4061 family members of 189 patients with various haematological neoplasms and two control groups: 955 relatives of 36 patients with non-malignant haematological disorders and 508 relatives of 33 patients with type II diabetes mellitus. Data collection included self-administered questionnaires. The odds ratio for haematological neoplasms among relatives of the index cases adjusted for age, sex, ethnicity, number of relatives in the family, and degree of familial linkage in the study group versus the two control groups was 3.62 (95% confidence interval, 1.44-9.07; P < 0.01). The vast majority of the haematological neoplasms among family members did not belong to the same histopathological category as the index cases. The data support the hypothesis of a genetic predisposition to haematological neoplasms. The fact that the aggregation is not disease specific is consistent with a defect in the pluripotent haemopoietic stem cell.

Adolescent↗

PubMed1994

Congenital haemolytic anaemia associated with adenylate kinase deficiency.

Chronic haemolytic anaemia associated with adenylate kinase (AK) deficiency is very rare and only seven cases in five families have been described. We present six children of one family who are deficient of this enzyme and in three of them a combined G6PD deficiency was found. AK deficiency was transmitted by an autosomal recessive gene and heterozygous state was not accompanied by disease, whereas homozygously affected individuals present a congenital chronic non-spherocytic haemolytic anaemia with haemoglobin levels of 8-9 g/dl. Patients also deficient in G6PD suffer from a more severe haemolytic anaemia with haemoglobin levels around 6 g/dl. The AK-deficient children are also mentally retarded. Splenectomy performed in five of the six patients resulted in complete remission of the haemolytic process.

Adenylate Kinase↗

PubMed1994

Familial leukemia: description of two kindreds and a review of the genetic aspects of the disease.

We describe two kindreds of Arab ancestry characterized by multiple cases of acute lymphoblastic leukemia. Consanguinity and intermarriages were prevalent in the two families. Age, mode of presentation, characteristics of the leukemic cells, response to treatment and prognosis were remarkably similar among the patients. A short review of the literature on familial leukemia is given.

Child↗

PubMed1994

Persistent abnormalities in red cell parameters following treatment of lymphoma.

Patients who have recovered from malignant lymphoma are at an increased risk of secondary acute leukemia (AL), and overt AL is frequently preceded by a myelodysplastic syndrome. Although the statistical risk is significant, only a minority of the patients will be so affected. We have reviewed peripheral blood counts of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) treated in the Departments of Hematology at the Edith Wolfson and Chaim Sheba Medical Centers, Israel. Included were only those who went into a complete remission and remained lymphoma free for extended periods. There were 85 patients with HD and 36 with NHL. In both groups peripheral blood counts at diagnosis were within the normal range. A prolonged follow-up (> 4 y), during which no further treatment was given, revealed a sustained increment over time of MCV (delta MCV) both in HD and NHL. A persistent monocytosis in HD patients was also evident. delta MCV was larger in HD. The difference at the end of the follow-up period was as follows: 10.1 fl + 11.8 in HD vs 5.0 fl + 6.2 in NHL, (P < 0.001). In addition, a significant loss of the normal correlation between the MCV and levels of hemoglobin was seen at the last follow-up. The change in MCV was present in all treatment groups, its magnitude increasing from radiotherapy to chemotherapy to combined radio chemotherapy. This trend is in analogy to the risk of secondary AL which is lower in NHL vs HD. Furthermore, it is lowest post radiotherapy and highest when both treatment modalities are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Biased representation of immunoglobulin heavy chain variable region subgroups in chronic lymphocytic leukemia.

The distribution of three immunoglobulin heavy chain variable region gene subgroups (VH1, 3 and 5) was investigated, using the polymerase chain reaction technique, in 53 patients with chronic lymphocytic leukemia. Thirty-seven patients displayed rearrangements of one of the above three gene segments. Over-representation of the VH5 subgroup was observed relative to its small size.

Antigens, CD↗

PubMed1993

Massive hematuria due to extramedullary plasmacytoma invading the bladder.

Bladder involvement by extramedullary plasmacytoma is a rare condition. A 46-year-old woman with known IgA-lambda multiple myeloma who developed this condition is described. The patient suffered from massive hematuria, which led to hypovolemic shock. Prompt supportive treatment by blood transfusions, fulguration of the bleeding mucosa and continuous bladder irrigation stopped the bleeding. Subsequent bladder irradiation lead only to partial response of the tumor.

Female↗

PubMed1993

Favorable response of pediatric AIDS-related Burkitt's lymphoma treated by aggressive chemotherapy.

We describe 4 male children infected by the human immunodeficiency virus (HIV) who developed Burkitt's lymphoma during their disease. The clinical picture was characterized by an insidious appearance of symptoms. All the children suffered for several months from abdominal discomfort and a gradual elevation of their blood lactic dehydrogenase (LDH) level prior to diagnosis. Bone marrow involvement was found in 2 of the patients and jaw involvement in the other 2. After confirming the diagnosis of Burkitt's lymphoma, they were treated according to conventional protocols, with no need to reduce the dose intensity. They all went into complete remission and did not suffer from major opportunistic infections during chemotherapy. None of them relapsed. Two patients died from opportunistic infections 1 and 3 years after diagnosis. The other 2 are alive, 7 years and 6 months after diagnosis. The various characteristics of this unique pediatric group are described and the comparison of the clinical picture in adults is made, together with a review of the relevant literature.

Adolescent↗

PubMed1993

Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.

Antibodies, Neoplasm↗

PubMed1993

Essential thrombocythemia: a relative benign long-term course.

The disease manifestations, response to therapy, and follow-up course of 35 patients with essential thrombocythemia seen in a single center were evaluated. The median age was 53 years (range 17-81). Twelve patients were asymptomatic on presentation and the diagnosis was incidental. Twenty-three patients presented with thrombocytosis-related symptoms, most commonly neurological, microcirculatory, or thromboembolic. In no patient did hemorrhage occur as a presenting symptom. The mean platelet count (+/- SD) at diagnosis was 858 +/- 223 x 10(9)/l and the mean maximal count during the follow-up period was 989 +/- 269 x 10(9)/l. The median follow-up of the entire group was 54 months (range 12-172). Ten of the 12 patients who were asymptomatic on presentation remained so during the observation period, while 10 patients who presented with thrombocytosis-related symptoms became asymptomatic following a single course of treatment with no recurrence of symptoms. Thirty of the 35 patients were treated with busulfan or hydroxyurea or both. Response to cytoreductive therapy was prompt and continuous in most patients. Essential thrombocythemia might be a disease of grave consequence but it seems that in general its course under treatment is more benign than previously thought.

Adolescent↗