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ABSTRACT: The present report summarizes our experience in applying a new approach in bone marrow transplantation for the treatment of β-thalassemia major. Ex-vivo pretransplant T-lymphocyte depletion with CAMPATH-1 was used for prevention of acute and chronic graft versus host disease and total lymphoid irradiation was added for the conditioning regimen for aborgation of potential rejection of T-cell depleted marrow allografts. Ten patients with homozygous β-thalassemia major were 9–48 months of age (median 18.5 months) and received HLA-identical allogeneic T-cell depleted marrow after treatment with total lymphoid irradiation, busulfan and cyclophos-phamide. Seven patients are alive and free of disease, 3–46 months post-transplantation. The actuarial probability of survival and of disease-free survival at two years was 70%. Three patients died: one of intracranial hemorrhage post-transplantation, one from busulfan interstitial pneumonitis, and one who rejected the first graft and developed fatal chronic graft versus host disease after a second transplant. Seven patients are alive and well with follow-up of 3–45 months, with no signs of acute or chronic GVHD. We conclude that T-cell depleted bone marrow transplantation is indicated for homozygous transfusion dependent young patients with β-thalassemia who are minimally transfused, particularly in areas where optimal conventional therapy is not feasible.
07/2009; 12(5-6):609-614.
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ABSTRACT: Chromatographic separation of labeled globin chains was performed on peripheral blood of 38 patients with homorygous β-thalassemia. In 11 patients globin synthesis was also studied in bone-marrow cells. The results showed β/α synthetic ratios in the common range of β+-thalassemia (from 0.11 to 0.39) in 16 out of 27 Kurdish Jews (59%) and in ten out of 11 Arabs (91%). In nine Kurdish Jews (33%) and in one Arab βd`-thalassemia was found. In a few patients from the latter group a very small peak was detected in the β region, which co-chromatographed with β-chains from non-thalassemic individuals, but apparently represents synthesis of a non-globin protein. In two affected siblings, synthesis of small amounts of β-chains was demonstrated in peripheral blood (β/α 0.018–0.025) and in one sample of bone-marrow cells (β/α 0.046). These ratios are lower than any previously reported in β+-thalassemia. Identification of the presumed β-peak in these patients was based on an approximate tenfold increase in β/α, γ/α and δ/α synthetic ratios measured in hemoglobin isolated by gel filtration. In eight pairs of siblings synthetic ratios were almost identical. β/α and β/α synthetic ratios were higher in bone-marrow cells than in peripheral blood. In bone-marrow cells γ-chain synthesis was lower, often resulting in a more marked chain inbalance (non-α versus α) than in peripheral blood particularly in patients with βd`-thalassemia.
07/2009; 1(4):333-347.
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ABSTRACT: Allogeneic cell-mediated immunotherapy with donor lymphocyte infusion (DLI) can successfully reverse chemoradiotherapy-resistant relapse in patients with chronic myeloid leukemia treated by allogeneic bone marrow transplantation (BMT). We describe the first successful attempt in 1992 to treat DLI-resistant relapse in a patient with CML in full hematologic relapse, using immunized donor lymphocytes. Donor lymphocytes were pulsed in vitro with a mixture of irradiated peripheral blood lymphocytes (PBL) obtained from both parents, in order to trigger alloactivation of donor lymphocytes against host alloantigens presented by parental cells, using as stimulating cells maternal PBL expressing the shared maternal haplotype and paternal PBL expressing the shared paternal haplotype of the patient. Full hematologic, cytogenetic and molecular remission was induced for the first time, independently of GVH, and has persisted for more than 9 years. To the best of our knowledge, this report represents the first successful immunotherapy with donor lymphocytes activated against host-type antigens. We suggest that immune donor PBL may be superior to DLI, possibly effective even when all other modalities fail, perhaps even independently of GVHD.
Bone Marrow Transplantation 11/2001; 28(8):795-8. · 3.75 Impact Factor
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ABSTRACT: Allogeneic bone marrow transplantation (BMT) or blood stem cell transplantation represents an important therapeutic tool for the treatment of otherwise incurable malignant and nonmalignant diseases. Until recently. autologous and allogeneic BMT or mobilized blood stem cell transplantation was used primarily to replace a malignant, genetically abnormal, or deficient immunohematopoietic compartment, and therefore highly toxic myeloablative regimens were considered mandatory for eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies have indicated that more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion following BMT. Thus eradication of blood cancer cells, especially in patients with chronic myelogenous leukemia and less frequently in patients with other hematologic malignancies, can frequently be achieved despite complete resistance of such tumor cells to the maximum tolerated doses of chemoradiotherapy. Our cumulative experience suggests that graft vs leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. Based on the cumulative clinical experience and experimental data in animal models of human diseases, it appears that induction of host vs graft tolerance as the first step may allow durable engraftment of immunocompetent donor lymphocytes, which may be used for induction of effective biologic warfare against host-type immunohematopoietic cells that need to be replaced, whether they are malignant, genetically abnormal, or self-reactive. Based on this rationale, we speculate that the therapeutic benefit of BMT may be increased by using safer conditioning as part of the transplantation procedure, with the goal of inducing host vs graft tolerance to enable subsequent induction of GVL, possibly graft vs tumor, or even graft vs autoimmunity effects, rather than attempting to eliminate host cells with hazardous myeloablative chemoradiotherapy. Our hypothesis suggests that effective BMT procedures might be accomplished without lethal conditioning of the host, using new, well-tolerated nonmyeloablative regimens, possibly minimizing immediate and late side effects related to myeloablative procedures. Recent clinical data suggest that effective BMT procedures may be accomplished with nonmyeloablative stem cell transplantation (NST) regimens, with no major toxicity. Thus new NST approaches may make BMT procedures safer for a spectrum of clinical indications in children and elderly individuals without lower or upper age limits, while minimizing procedure-related toxicity and mortality. Our cumulative data suggest that high-dose chemotherapy and radiation therapy may be successively replaced by more effective alloreactive donor lymphocytes, thus setting the stage for innovative therapeutic procedures with safer and more effective treatment of patients requiring BMT.
Cancer Chemotherapy and Pharmacology 09/2001; 48 Suppl 1:S79-84. · 2.83 Impact Factor
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ABSTRACT: Allogeneic bone marrow or blood stem call transplantation (BMT) represents an important therapeutic tool for the treatment of otherwise incurable malignant and non-malignant diseases. Until recently, autologous and allogeneic bone marrow and mobilized blood stem cell transplantations were used primarily to replace malignant, genetically abnormal or deficient immunohematopoietic compartments, and therefore highly toxic myeloablative regimens were considered to be mandatory for the effective eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies have indicated that much more effective eradication of the host immunohematopoietic system cells can be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion following BMT. Thus, eradication of blood cancer cells, especially in patients with chronic myeloid leukemia and, less frequently, in patients with other hematologic malignancies, can frequently be accomplished despite the complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience has suggested that graft-vs.-leukemia (GVL) effects might be a useful tool for the eradication of otherwise resistant tumor cells of host origin. Based on the cumulative clinical experience and experimental data in animal models of human diseases, it appears that the induction of host-vs.-graft tolerance as an initial step may allow the durable engraftment of donor immunocompetent lymphocytes, which may be used for the induction of effective biologic warfare against host-type immunohematopoietic cells that need to be replaced, including malignant, genetically abnormal or self-reactive cells. Based on the aforementioned rationale, we speculated that the therapeutic benefit of BMT may be improved by using safer conditioning as part of the transplant procedure, with the goal being to induce host-vs.-graft tolerance to enable subsequent induction of GVL, possibly graft-vs.-tumor or even graft-vs.-autoimmunity effects, rather than attempting to eliminate host cells with hazardous myeloablative chemoradiotherapy. This hypothesis suggested that effective BMT procedures could be accomplished without lethal conditioning of the host, using new well-tolerated non-myeloablative regimens, thus possibly minimizing immediate and late side-effects related to the myeloablative procedures until recently considered to be mandatory for the conditioning of BMT recipients. Recent clinical data presented in this review suggest that effective BMT procedures may be accomplished with well-tolerated non-myeloablative stem cell transplantation (NST) regimens, with no major toxicity. Thus, new NST approaches may offer the feasibility of safer BMT procedures for a large spectrum of clinical indications in children and elderly individuals, without lower or upper age limits, while minimizing procedure-related toxicity and mortality. Taken together, our data suggest that high-dose chemotherapy and radiation therapy may be successfully replaced by a more effective biologic tool, alloreactive donor lymphocytes, thus setting the stage for innovative therapeutic procedures for safer and more effective treatment of patients in need of BMT.
Reviews in Clinical and Experimental Hematology 07/2001; 5(2):135-46.
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ABSTRACT: Patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, intravenous immunoglobulin, and splenectomy. We describe the cases of two patients with refractory autoimmune thrombocytopenia treated with oral cyclosporin A (CsA) to evaluate the efficacy of this alternative therapy. Blood pressure and hepatic and renal function were in the normal range before initiation of treatment. Induction therapy with pulses of high-dose methylprednisolone was used for 3 consecutive days to improve the initial immune suppression. Gradual dose reduction of CsA, according the platelet count, minimized the long-term adverse effects of CsA. Oral CsA with pulses of high-dose methylprednisolone induced remission of the thrombocytopenia. Gradual weaning of CsA over months, according the platelet count, produced no observable adverse effects of the CsA. Rapid dose reduction caused thrombocytopenia, which resolved with higher dosages of CsA. Our cases show the efficacy of CsA for refractory immune thrombocytopenia. This therapeutic option with oral CsA as an additional salvage option may avoid splenectomy and the adverse effects of long-term corticosteroids. Larger clinical investigations are necessary to establish the indications and therapeutic regimen for CsA in immune thrombocytopenia.
European Journal Of Haematology 06/2001; 66(5):347-51. · 2.61 Impact Factor
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E Naparstek,
M Delukina,
R Or,
A Nagler,
J Kapelushnik,
G Varadi,
N Strauss, G Cividalli,
M Aker,
C Brautbar,
H Waldmann,
G Hale,
S Slavin
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ABSTRACT: We have analyzed the factors associated with engraftment in 216 recipients of T-cell depleted allogeneic HLA identical sibling marrow transplants using Campath 1 monoclonal antihuman lymphocyte (CD52) antibodies. The patient population consisted of 168 patients with hematologic malignancies, 26 with severe aplastic anemia (SAA), and 22 with hemoglobinopathies, half of whom received marrow treated in vitro with Campath-1M (IgM) and half received marrow with Campath-1G (IgG2b isotype). Patients with durable engraftment had fast hematopoietic recovery: SAA patients reached ANC > 0.5 x 10(6)/L on Day 14; those with leukemia attained ANC > 0.5 x 10(6)/L on Days 18, 17, and 15 for ANLL, ALL and CML respectively, while patients with thalasemia reached ANC > 0.5 x 10(6)/L on Day 21. Overall, 24 patients (17 with leukemia, 4 with SAA, and 3 with thalassemia) suffered graft failure: 10 patients (all grafted with Campath-1M) rejected their grafts, while 14 others (9 grafted with Campath-1M, and 5 with 1G isotype) never engrafted (p = 0.009). Multivariate analysis revealed that neither pretransplant protocol, nor stage of disease or type of antibody used, donor sex and ABO match had any impact on engraftment. The variables favorably associated with engraftment were older age (p = 0.030, RR = 1.016) and CFU-GM number (p = 0.013, RR = 1.001). Patients with ANLL or SAA had a better chance to engraft (p = 0.027, RR = 1.400; and p = 0.003, RR = 2.677, respectively) compared to patients with thalassemia (p = 0.001, RR = 0.551). A higher concentration of Campath-1 antibody in vitro and in vivo adversely affected engraftment. Our data show that satisfactory engraftment can be achieved in patients transplanted with Campath-1 treated marrow allografts. However, despite the measures undertaken to prevent rejection, graft failure still poses a problem. Further pretransplant immunosuppression and perhaps more selective T-cell depletion may reduce the increased graft failure in these patients.
Experimental Hematology 07/1999; 27(7):1210-8. · 2.90 Impact Factor
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ABSTRACT: Graft-versus-host disease (GVHD), graft rejection, disease recurrence and long-term toxicity remain significant obstacles to successful allogeneic bone marrow transplantation (BMT) in children with genetic diseases. In an attempt to improve results, we used a preparative regimen consisting of three alkylating agents, busulfan (BU), thiotepa (TTP) and cyclophosphamide (CY), for T cell-depleted allogeneic bone marrow transplantation instead of the conventional BU-CY protocol. The effect of this intensified regimen was investigated in 26 consecutive children with genetic diseases who underwent T cell-depleted BMT from HLA-identical siblings. Sixteen patients were males and 10 females, of median age 5 (0.2-14) years. The diseases included beta-thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott-Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/kg x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1). Engraftment was as expected, with WBC >1.0 x 10(9)/l at day +19 (10-33), ANC >0.5 x 10(9)/l at day +22 (10-56) and platelets >25 x 10(9)/l at day +32 (18-131). Transplant-related mortality was 19%. Overall survival and disease-free survival (DFS) at 60 months follow-up were both 77%. Our results with the BU-TTP-CY regimen followed by T cell-depleted BMT in genetic diseases may provide a basis for prospective comparison with the standard conditioning regimen of BU-CY in the management of children suffering from these conditions.
Bone Marrow Transplantation 05/1999; 23(9):861-5. · 3.75 Impact Factor
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S Slavin,
A Nagler,
E Naparstek,
Y Kapelushnik,
M Aker, G Cividalli,
G Varadi,
M Kirschbaum,
A Ackerstein,
S Samuel,
A Amar,
C Brautbar,
O Ben-Tal,
A Eldor,
R Or
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ABSTRACT: Myeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 x 10(9)/L whereas 2 patients never experienced ANC < 0.5 x 10(9)/L. ANC > or = 0.5 x 10(9)/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 x 10(9)/L in 4 patients requiring no platelet support at all; overall platelet counts > 20 x 10(9)/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.
Blood 03/1998; 91(3):756-63. · 9.90 Impact Factor
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ABSTRACT: The incidence and clinical course of nosocomial septicemia with Streptococcus viridans was evaluated prospectively in 242 consecutive bone marrow transplant (BMT) recipients throughout their 15-213 days' (median 47) hospitalization, including 4-58 days (median 18) of neutropenia. Initial empiric therapy for febrile neutropenia consisted of mezlocillin, gentamicin and cefazolin; glycopeptide was excluded. S. viridans septicemia occurred in 23/209 (11%) subjects with underlying malignant disease, and only during neutropenia with concomitant mucositis: in 20 subjects (four with ampicillin-resistant strains), S. viridans septicemia occurred at onset of febrile neutropenia, 1-5 days (median 4.5) post-BMT. All survived with an uncomplicated clinical course. Thus, glycopeptide seems unnecessary in the initial empiric antibiotic regimen. The other three subjects demonstrated S. viridans septicemia (two with ampicillin-resistant strains) on day 11 post-BMT; two died. The major risk identified was cytosine arabinoside administration in the conditioning regimen (P < 0.01).
Bone Marrow Transplantation 11/1995; 16(4):565-70. · 3.75 Impact Factor
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ABSTRACT: Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre-BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.
Blood 11/1995; 86(8):3241-6. · 9.90 Impact Factor
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ABSTRACT: A 6-month-old child with familial hemophagocytic lymphohistiocytosis (FHL) experienced early sequential pneumonia due to respiratory syncytial virus (RSV) and cytomegalovirus (CMV) following bone marrow transplantation (BMT). The patient was deficient in natural killer (NK) cell activity (as found frequently in patients with FHL), and this risk factor may have played a major role in the concomitant infection by the two viral pathogens. Rapid diagnostic methods for both viruses are essential and early specific treatment may serve to ameliorate RSV- and CMV-induced lung injury in these life-threatening infections.
Journal of Medical Virology 07/1995; 46(2):169-71. · 2.82 Impact Factor
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ABSTRACT: One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34) and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases.
British Journal of Haematology 04/1995; 89(3):506-15. · 4.94 Impact Factor
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ABSTRACT: Allogeneic BMT for severe aplastic anemia is associated with a significant rate of graft rejection, especially in patients who have been previously transfused. We report a child with aplastic anemia who rejected donor marrow twice despite adequate immunosuppression as part of the conditioning therapy but engrafted successfully following combined administration of three modalities of immunosuppression: antithymocyte globulin, total lymphoid irradiation and the monoclonal antibody Campath-1G. Restriction fragment length polymorphism studies > 1 year after BMT show full donor hematopoiesis with no evidence of autologous recovery.
Bone Marrow Transplantation 01/1994; 13(1):97-9. · 3.75 Impact Factor
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Transplantation Proceedings 07/1993; 25(3):2375-6. · 1.00 Impact Factor
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ABSTRACT: Multiple plasmacytomas with IgA paraproteinemia, a low grade lymphoid neoplasm of differentiated B cells rarely seen in the young, were encountered in a 10-year-old child. T cell-depleted allogeneic bone marrow transplantation (BMT) was performed because of progressive disease despite chemotherapy. Donor T cells were infused after transplantation in gradually increasing numbers to achieve a graft-versus-tumor effect. Complete eradication of all tumor masses was achieved following BMT with normalization of serum immunoglobulin levels. The patient remains in complete remission 4 years after BMT. Allogeneic BMT should be considered early in the course of low-grade lymphoid malignancy in the younger age group.
Bone Marrow Transplantation 11/1992; 10(4):381-2. · 3.75 Impact Factor
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ABSTRACT: A relatively simple method for extraction of free fatty acids from cerebrospinal fluid with aminopropyl bonded-phase columns, and the estimation of palmitic acid (C16:0) and stearic acid (C18:0) concentrations by high-performance liquid chromatographic analysis is described. The values of C16:0 and C18:0 in patients with non-neurological disorders lie within a narrow range, with a mean (+/- S.D.) of 4.02 +/- 0.33 micrograms/ml for C16:0 and 2.72 +/- 0.39 micrograms/ml for C18:0.
Journal of Chromatography 05/1991; 565(1-2):424-9. · 4.53 Impact Factor
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Transplantation Proceedings 03/1989; 21(1 Pt 3):3053-4. · 1.00 Impact Factor
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Progress in clinical and biological research 02/1989; 309:217-22.
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ABSTRACT: Two children with typical clinical and haematological features of monosomy 7 myeloproliferative syndrome are presented. Both children displayed decreased production of beta-globin chains and unbalanced high alpha/non-alpha synthetic ratios similar to those characteristic of homozygous beta-thalassaemia. These provide further evidence for the involvement of the erythroid line as part of the malignant clone, indicating neoplastic transformation of a pluripotential stem cell in this disease.
British Journal of Haematology 04/1988; 68(3):357-62. · 4.94 Impact Factor
