N Jamal

University of Toronto, Toronto, Ontario, Canada

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Publications (42)220.3 Total impact

  • Biology of Blood and Marrow Transplantation - BIOL BLOOD MARROW TRANSPLANT. 01/2007; 13(2):42-42.
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    ABSTRACT: The erythropoietic effect of recombinant human erythropoietin, epoetin alpha (rHuEPO), in promoting the growth of erythroid burst-forming units (BFU-E) was compared with darbepoetin alpha (DARB), a rHuEPO analogue obtained by site-directed mutagenesis. Human bone marrow cells derived from healthy donors were cultured with different concentrations of rHuEPO or DARB for 12 - 21 days and BFU-E were counted using an inverted microscope. The EC50 of rHuEPO was about 10-fold lower than DARB and the size of the colonies was significantly larger in rHuEPO-containing cultures using comparable concentrations. The maximum number of colonies obtained in some rHuEPO-containing cultures was also higher than for DARB. The number of colonies in DARB-containing cultures was increased, in part, by the addition of low concentrations of rHuEPO, but not by DARB, even at high concentrations. We conclude that DARB is not as effective as rHuEPO in supporting the in vitro growth of human BFU-E.
    The Journal of international medical research 01/2006; 34(1):42-51. · 0.96 Impact Factor
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    ABSTRACT: Pre transplant screening work-up of donors for allogeneic blood and marrow transplantation is essential in an effort to minimize risks to the recipient and protect the donor. At Princess Margaret Hospital, every potential donor is screened with a bone marrow aspirate. The case histories of three asymptomatic potential donors who presented within 1 year with normal complete blood counts, history and physical examination are presented. A 65-year-old male patient was diagnosed with smouldering multiple myeloma, a 72-year-old male patient with chronic lymphocytic leukemia and a 42-year-old male patient with myelodysplastic syndrome. Bone marrow examination led to the diagnosis in each one of these cases. Of note is that each of the potential donors was discovered to have the same disease as the transplant recipient. In vitro clonogenic hemopoietic progenitor assays were compared to those of 20 normal volunteers. Inferior growth of hemopoietic progenitor colonies in all three was noted. In conclusion, particularly in older donors and donors with potential for familial malignancies, more screening investigations including bone marrow aspiration may be reasonable to investigate for occult hematological malignancies prior to stem cell donation. Clonogenic assays can contribute to detect hemopoietic abnormalities pre transplant.
    Bone Marrow Transplantation 05/2004; 33(8):855-8. · 3.54 Impact Factor
  • Journal of Thrombosis and Haemostasis 09/2003; 1(8):1848-50. · 6.08 Impact Factor
  • Biology of Blood and Marrow Transplantation - BIOL BLOOD MARROW TRANSPLANT. 01/2003; 9(2):132-133.
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    ABSTRACT: Benchmark analysis of patients with chronic myeloid leukemia (CML) alive for more than 10 years after allogeneic bone marrow transplantation (BMT) including data on disease status, bone marrow reserve, long-term complications, and quality of life (QOL). Eighty-nine patients (46 in first chronic phase, 43 in advanced phase) received an allogeneic BMT for CML during the study period. Medical outcomes and QOL of patients were analyzed retrospectively. Twenty-eight (31.5%) of 89 patients were alive at 10 years and included in this analysis. Thirteen (46.4%) of 28 long-term survivors never relapsed. Fifteen patients relapsed between 0.5 and 16 years after transplantation. Ten patients showed a hematologic relapse and received salvage treatment. Five patients showed transient low levels of BCR-ABL-positive cells by Southern blot with no subsequent hematologic relapse. One of the 28 patients died in blast crisis at 12 years. The most frequent long-term complications were chronic graft-versus-host disease, osteoporosis, and cataracts. Frequency of clonogenic progenitors remained persistently decreased. QOL assessment yielded lower scores in physical performance as compared with an age-matched normative population, whereas social functioning was equivalent. A high degree of satisfaction was noted with interpersonal relationships. Patients with CML surviving their BMT long term do well in terms of medical outcomes. A constant rate of relapse was noted, with a high salvage rate of affected patients, suggesting the need for lifelong monitoring. QOL is perceived as good, particularly as related to social functioning; however, it is inferior to a normative population with regard to physical performance.
    Journal of Clinical Oncology 06/2002; 20(9):2334-43. · 18.04 Impact Factor
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    ABSTRACT: Patients with CML post allogeneic BMT or during treatment with Interferon were monitored in bone marrow and peripheral blood for BCR-ABL transcripts by RT-PCR and in the majority of cases also by Southern blotting. Bone marrow and peripheral blood samples were obtained simultaneously and tested by RT-PCR with the objective to determine the usefulness to follow CML patients by testing peripheral blood rather than bone marrow samples. For the purpose of this study we have considered the test results obtained from bone marrow samples as the standard. A total of 111 CML patients were examined who underwent either an allogeneic BMT (n=91) or were treated with Interferon (n=20) amounting to a total of 163 assessments for BCR-ABL. Concordance of results was observed in 153 samples (93.9%). 10 samples showed discordance. Seven of these were subjected to repeat testing by RT-PCR. The previously obtained discordant results were confirmed. The sensitivity of peripheral blood assays was calculated to be 96.2% with a specificity of 89.5%. RT-PCR results restricted to Southern blot negative patients showed concordance of bone marrow and peripheral blood in 91.1% of tested samples with a sensitivity of 92.7% and a specificity of 88.6%. The subset of patients in which Southern blot testing was not available showed concordance at a similar level. Complete concordance was seen in all patients that were found to be positive by Southern blotting. We conclude from this study that peripheral blood testing for BCR-ABL transcripts by RT-PCR is a test with high sensitivity and specificity and may potentially replace bone marrow testing. This approach will probably result in a high level of acceptance by patients and may permit more frequent monitoring.
    Leukemia and Lymphoma 09/1999; 34(5-6):493-500. · 2.30 Impact Factor
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    ABSTRACT: Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 microg/kg/day) (group 1) and 20 mobilized with 10 microg/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 x 10(6) CD34+/kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34,643 vs $37,354) but the mean overall cost for both groups was similar at 100 days ($46,334 vs $46,083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT.
    Bone Marrow Transplantation 01/1999; 22(12):1199-205. · 3.54 Impact Factor
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    ABSTRACT: A major limitation of unrelated bone marrow transplantation is the duration of time that is safe between harvest and re-infusion of the marrow. We have been able to demonstrate safe re-infusion of bone marrow kept at room temperature during transport, after almost 36 h. In vitro colony-forming assays suggest that stability may be as long as 5 days.
    Bone Marrow Transplantation 12/1997; 20(9):785-6. · 3.54 Impact Factor
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    ABSTRACT: Progress in understanding the abnormal regulation of hematopoiesis in chronic myelogenous leukemia (CML) would be facilitated if neoplastic cells, at all stages of the disease, could be studied in an animal model. In this report, we show that irradiated severe combined immunodeficient (SCID) mice can be transplanted with both normal (Philadelphia chromosome [Ph]-negative) and neoplastic (Ph+) cells from CML patients with either chronic or blast phase disease. Mice transplanted with peripheral blood (PB) or bone marrow (BM) cells from 9 of 12 chronic phase CML patients were well engrafted with human cells including multilineage colony-forming progenitors and CD34+ cells for at least 90 days posttransplantation. Repeated posttransplant injections of cytokines did not enhance the number of engrafted human cells. Interestingly, approximately 70% of the human progenitors found in the engrafted SCID BM were Ph-, suggesting that the growth of primitive normal cells is favored in this in vivo transplant model. A similar number of normal cells were found in mice transplanted with either PB or BM cells, suggesting that elevated numbers of primitive normal cells are present in CML PB. When cells from patients with CML in either myeloid or lymphoid blast crisis were transplanted into SCID mice, the BM of these mice was more rapidly repopulated and to a higher level than that observed with transplants of chronic phase cells. Moreover, all human colony-forming progenitors present in the BM of mice transplanted with blast crisis cells were Ph+, and the majority of cells showed the same morphological features of the blast crisis cells originally transplanted. These experiments provide a starting point for the creation of an animal model of CML and establish the feasibility of using this model for the future characterization of transplantable CML stem cells during disease progression.
    Blood 03/1996; 87(4):1539-48. · 9.06 Impact Factor
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    ABSTRACT: This paper describes a culture system which supports the formation of B cell and some T cell colonies under serum-free conditions in peripheral blood samples of normal individuals and patients with chronic lymphocytic leukemia (CLL) of B cell type. In this system, serum is replaced by bovine serum albumin, transferrin, cholesterol, insulin and catalase or horseradish peroxidase. In addition, it is necessary to add staphylococcus protein A, mitomycin-treated T cells as feeders and phytohemagglutinin leukocyte-conditioned medium as a source of growth factors. The plating efficiency is greatly enhanced when normal cells are incubated with galactose oxidase prior to plating and when CLL cells are exposed sequentially to neuraminidase and galactose oxidase.
    Stem Cells 12/1995; 5(6):480 - 491. · 7.70 Impact Factor
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    ABSTRACT: Interleukin 6 (IL6) plasma levels were measured in 63 patients with multiple myeloma and 8 individuals with benign monoclonal gammopathy. 15 of these 71 samples showed by an enzyme linked immunosorbent assay (ELISA) detectable levels that ranged from 5 to 107 pg of IL6/ml. The IL6 levels of patients with multiple myeloma did not differ significantly from those of normal individuals (N = 25, range 5-27 pg IL6/ml) (Student's t-test, p = 0.295). The samples were negative for IL4; 3 were found positive for IL1 beta. A correlation between IL6, IL4 and IL1 beta levels and disease status was not observed for this group of patients.
    Leukemia and Lymphoma 08/1994; 14(3-4):335-40. · 2.30 Impact Factor
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    ABSTRACT: We report the case of a patient with acute myeloid leukemia in second remission who received an allogeneic bone marrow transplant from an immunosuppressed HLA-identical sibling donor. The donor was receiving prednisone, azathioprine and cyclosporine for a cadaveric renal allograft. Bone marrow growth in culture from the donor was normal. Engraftment was within normal limits. Moderate acute graft-versus-host disease (GVHD) developed. We suggest that transplants from immunosuppressed donors are feasible and that this does not preclude the development of GVHD.
    Bone Marrow Transplantation 07/1994; 13(6):831-3. · 3.54 Impact Factor
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    ABSTRACT: A 20-year-old woman presented with polycythemia vera and was treated with phlebotomy alone for eleven years, following which all clinical manifestations of the disease disappeared. The clinical remission with normal physical findings and normal peripheral blood counts has persisted for a further 11 years. Erythroid colony culture results have paralleled the clinical state. Initial bone marrow cultures revealed spontaneous growth of erythroid burst-forming units (BFU-E). Subsequent cultures of peripheral blood cells throughout most of the period of spontaneous clinical remission have revealed little or no spontaneous growth of BFU-E. This suggests a suppression of the abnormal stem cell clone during the period of remission.
    American Journal of Hematology 06/1994; 46(1):54-6. · 4.00 Impact Factor
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    ABSTRACT: This paper reports on the preclinical evaluation of merocyanine 540 (MC540) as an agent for the inactivation of tumour cells in BM grafts from non-Hodgkin's lymphoma (NHL) patients. The three cell lines used for this study, OCI-LY13.1, OCI-LY13.2 and OCI-LY9, originate from two patients with high-grade NHL. The OCI-LY13.1 and OCI-LY13.2 lines are derived from the same patient. The OCI-LY13.1 line was established at the time of diagnosis while the OCI-LY13.2 line was established after the tumour had become refractory to therapy. When used under conditions that are known to preserve about 50% of normal human pluripotent hematopoietic progenitor cells (CFU-GEMM), MC540-sensitized photoirradiation reduced in vitro clonogenic OCI-LY9 cells by 4 orders of magnitude and OCI-LY13.1 and OCI-LY13.2 cells by > or = 5. Survival curves for OCI-LY13.1 and OCI-LY13.2 cells were similar and followed first order kinetics, while those for OCI-LY9 cells were distinctly biphasic. Suspension cultures established with photoinactivated lymphoma cells confirmed that MC540-sensitized photoirradiation was cytotoxic and capable of eliminating > or = 4 log of tumour cells. These results encourage the further exploration of MC540-sensitized photoirradiation as a means to purge autologous marrow grafts from NHL patients.
    Bone Marrow Transplantation 10/1993; 12(3):191-6. · 3.54 Impact Factor
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    ABSTRACT: The cytotoxicity of a recombinant interleukin 6 (IL-6)-diphtheria toxin (DT) fusion protein towards human myeloma cell lines was investigated. DAB389-IL-6 inhibited protein synthesis and methylcellulose colony formation by U266 myeloma cells. In the clonogenic assay, the fusion protein approached the level of cytotoxicity achieved by native DT. The specificity of killing by DAB389-IL-6 was demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL-6. The effect of DAB389-IL-6 on colony formation by six OCI-My cell lines was assessed. Similar to U266 cells, colony growth by the OCI-My 5 and -My 2 cell lines was inhibited in a simple dose dependent manner. However, a biphasic effect was observed for the IL-6 dependent OCI-My 4 cells; DAB389-IL-6 stimulated colony formation at low (< or = 10(-11) M) concentrations, yet was inhibitory at higher doses. Three other cell lines whose growth was not altered by IL-6 were relatively unaffected by DAB389-IL-6, despite their sensitivity to native DT. Flow cytometric analysis for IL-6 receptor expression using phycoerythrin-conjugated IL-6 demonstrated specific binding sites on both DAB389-IL-6 sensitive and certain insensitive cell lines, suggesting that other factors in addition to the expression of IL-6 receptors are involved in killing by the fusion toxin. Despite evidence for a role of IL-6 in myeloid cell development, normal bone marrow was insensitive to the IL-6 fusion toxin. In cultures containing both normal bone marrow and U266 cells DAB389-IL-6 effectively inhibited the growth of U266 myeloma colonies but had little effect on normal bone marrow erythroid, granulocyte and mixed erythroid/granulocyte colony growth. From these experiments we conclude that DAB389-IL-6 is specifically cytotoxic towards a subset of IL-6-responsive human myeloma cell lines and may be useful, in some cases, in the selective elimination of tumour cells from mixed populations of normal and malignant cells.
    British Journal of Haematology 10/1993; 85(1):25-36. · 4.94 Impact Factor
  • H A Messner, N Jamal
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    ABSTRACT: A number of cell culture techniques are now available to evaluate clonogenic hematopoietic progenitors as well as cell populations that represent an interactive network of cells with regulatory capabilities. Although clonogenic cells in allografts do not appear to be correlated with the time to recovery, they seem to predict their time to engraftment in autografts. However, these cell populations are likely to be only surrogate measurements because a reduction by various purging techniques does not seem to alter the ability of autografts to reestablishing hematopoiesis. Currently, it is not known whether or not these differences may relate to differences in the preparative regimens, graft-versus-host disease prophylaxis, or other differences in the management, such as administration of high concentrations of various antiviral agents. It is also now possible to measure growth factor production following the transplant procedure and to correlate the availability of endogenous factors and recovery after a transplant. Under normal conditions, the activity levels appear to return to normal values within 20-30 days, whereas in patients with late engraftment one may observe prolonged elevation of growth factors. If confirmed, this would suggest that in bone marrow transplants a delayed return is more related to reduced progenitor cells rather than a deficiency of growth factors.
    Journal of Hematotherapy 02/1993; 2(1):19-25.
  • H A Messner, Y Hirota, N Jamal
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    ABSTRACT: The suboptimal return of hematopoietic precursors after bone marrow transplantation is suggestive of a limited bone marrow reserve in recipients of allografts. The problem does not appear to lie in the ability to produce some of the well-known hematopoietic growth factors such as G-CSF or activities considered to stimulate megakaryocytopoiesis. The persistence of factor production in patients with slow returning counts is suggestive of either a defect in the repopulating cells or in the function of the microenvironment that is not reflected in the production of factors that can be measured in the plasma. A defect in the graft may be overcome by altering the composition of engrafting cells. As seen in autologous transplants the addition of peripheral blood stem cells may be effective in reducing the period to engraftment. Putative defects in the microenvironment have to be addressed by further studies. Exogenously added stroma related factors such as kit ligand or IL-11 may be effective in correcting the deficiency.
    Journal of Hematotherapy 02/1993; 2(3):343-5.
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    ABSTRACT: Peripheral blood cells of a patient with diffuse large cell non-Hodgkin's lymphoma presenting with hypereosinophilia were used to establish an EBV negative lymphoma cell line termed OCI-Ly17. Cells of the line stained positive for CD2 and CD5 determinants and demonstrated rearrangement of the T-cell receptor beta chain. The immunoglobulin heavy chain gene was found to be in germ line configuration. Northern blot studies using probes for IL-1 alpha, IL-3, IL-4, IL-5, IL-6, and GM-CSF showed message for IL-5 and IL-6. Supernatants of the cell line were evaluated on normal non-adherent, E-rosette depleted bone marrow cells to determine the presence of growth promoting activities for clonogenic eosinophilic progenitors. Eosinophilic colonies were observed. Their frequency depended upon the amount of supernatant added to the cultures. The growth promoting activity in the supernatant was reduced in a dose dependent manner by preincubation with increasing concentrations of anti-IL-5 antibodies. The supernatants of the cell line were also tested on the IL-6 sensitive human myeloma line OCI-My4 and myeloma colonies grew in response. This stimulatory activity within the supernatant was neutralized by addition of increasing concentrations of anti-IL-6 antibodies. Although producing IL-5 and IL-6 constitutively, the lymphoma line did not increase proliferation in response to either interleukin, nor did it show a reduced proliferative rate when antibodies to IL-5 or IL-6 were added to the cultures.
    Leukemia and Lymphoma 10/1992; 8(1-2):97-107. · 2.30 Impact Factor
  • Y Hirota, N Jamal, H A Messner
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    ABSTRACT: Blast cell colonies can be grown reproducibly in methylcellulose from normal human mononuclear bone marrow cells (MNC) in the presence of 30% human plasma, 1 U human recombinant erythropoietin and 10% of medium conditioned by phytohemagglutinin stimulated leukocytes as a source of growth factors. The colonies can be recognized by inverted microscopy by their display of highly refractile cytoplasmic structures that resemble small vacuoles. A proportion of cells within these colonies remains CD34-positive (CD34+). The blast-like morphology of these cells was sustained for at least 14 to 21 days. The frequency of blast cell colony forming units (CFU-BL) can be increased by a series of separation procedures to produce E-rosette depleted, nonadherent cells (E-NAC), CD34+ cells and CD33-CD34+ cells. The mean number of CFU-BL per 10(5) cells was 1.9 +/- 1.6 in MNC, 5.7 +/- 2.7 in E-NAC, 108 +/- 51 in CD34+ cells and 112 +/- 109 in CD33-CD34+ cells. The enrichment procedures were not specific for CFU-BL but also resulted in a similar increase of multilineage and single lineage progenitors. The relative proportions of CFU-BL and other progenitors remained unchanged among these subpopulations. The size of individual blast cell colonies on day 16 varied from 20 to 1,600 cells. After 14 to 21 days, cells within blast cell colonies acquired mature morphological features. The majority of blast cell colonies developed into multilineage colonies (62%); some (38%) were restricted to a single hemopoietic lineage. Larger blast cell colonies had a higher probability of developing into multilineage colonies than smaller blast cell colonies.
    International journal of cell cloning 08/1992; 10(4):241-8.