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H T Greinix

Publications and source records attributed to H T Greinix.

69 records · Page 4Linked to original sources
PubMed1997

Relapse of Philadelphia chromosome positive acute lymphoblastic leukaemia after marrow transplantation: sustained molecular remission after early and dose-escalating infusion of donor leucocytes.

We present a patient who underwent sibling allogeneic BMT because of refractory Ph+ve ALL and remained BCR-ABL-positive after marrow grafting. Haemopoietic precursor cells were predominantly BCR-ABL-negative and of donor origin. In T cells an exclusively donor genotype was demonstrated. Despite donor leucocyte infusion (DLI), 20 weeks after BMT BCR-ABL fusion mRNA increased in semiquantitative polymerase chain reaction and leukaemic infiltration of the patient's bone marrow was seen. After a second course of DLI the patient achieved sustained molecular remission but he developed severe graft-versus-host disease (GvHD) and died from bacterial sepsis 9 months after DLI.

Adult↗
PubMed1996

Long-term leukemia-free survival after allogeneic marrow transplantation in patients with acute myelogenous leukemia.

Between February 1982 and April 1995, 62 patients (37 male, 25 female) with acute myelogenous leukemia (AML) with a median age of 32 years (19-51 years) received allogeneic marrow grafts from an HLA-identical sibling (n=60) or an HLA-mismatched family member (n=2). At the time of transplant, 35 patients were in first complete remission (CR), five in second CR, eight were primary refractory, eight were in untreated relapse and six in refractory relapse. The FAB subtypes were as follows: M1 (n=17), M2 (n=13), M3 (n=6), M4 (n=19), M5 (n=6), M6 (n=1). For conditioning most patients were given total body irradiation combined with cyclophosphamide (CY, n=50) or CY and busulfan (n=9). For graft-versus-host disease prophylaxis patients received cyclosporin A (CSA) and methotrexate (MTX) (n=32), MTX alone (n=12), CSA and methylprednisone (n=5), or CSA alone (n=13). As of April 1995, probability of leukemia-free survival projected at 10 years after BMT was 60% for patients transplanted in first CR compared with 10% for patients transplanted beyond first CR. Transplant-related mortality was 11% after BMT in first CR and 39% after BMT beyond first CR. Probability of relapse projected at 10 years after BMT is 32% for patients who received transplants in first CR and 81% for patients who received transplants beyond first CR. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a high curative potential for patients with AML who receive transplants in first CR and offers the chance of long-term disease-free survival for some patients with advanced disease.

Acute Disease↗
PubMed1996

Graft failure after donor leucocyte infusion in relapsed chronic myeloid leukaemia: successful treatment with cyclophosphamide and antithymocyte globulin followed by peripheral blood stem cell infusion.

We report a patient with chronic myeloid leukaemia who underwent allogeneic marrow transplantation (BMT) but had a molecular relapse 5 months and haematological relapse 15 months after BMT. Since therapy with alpha-interferon had been ineffective he received leucocyte infusions from his sibling donor. He developed acute graft-versus-host disease and became aplastic 6 weeks later. Despite donor marrow infusion and cytokine stimulation marrow aplasia persisted for 13 weeks. Then, donors' peripheral blood stem cells were given after conditioning with cyclophosphamide and antithymocyte globulin resulting in trilineage engraftment of donor haemopoiesis. Since then, the patient has been in continuous molecular remission for 11 months.

Antilymphocyte Serum↗
PubMed1996

G-CSF stimulation of donor myelopoiesis prolongs survival of relapsed BCR-ABL-positive acute lymphoblastic leukemia after allogeneic marrow transplantation.

An allogeneic sex-mismatched BMT which was performed in a male patient with BCR-ABL-positive ALL in second hematological and central nervous system relapse resulted in a CR for 12 months. After BMT, the patient was closely monitored with reverse transcription (RT)-PCR. One month before a third relapse RT-PCR became positive. During relapse G-CSF was administered. It specifically stimulated the donor-derived myelopoiesis and led to the stabilization of the disease for 8 months. Fluorescence in situ hybridization analyses of individual cell populations revealed that during the whole course of G-CSF administration granulocytes, CD4+, CD8+ and CD34+/CD10- cells were of female (donor) origin and only the CD34+/CD10+ cells which represented the leukemic blasts, were of male (host) origin.

Adult↗
PubMed1995

Microangiopathy following allogeneic marrow transplantation. Association with cyclosporine and methylprednisolone for graft-versus-host disease prophylaxis.

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center. The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms. We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n = 70) at our institution. All patients in both groups engrafted. Day 100 survival (80% vs. 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups. CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P < 0.01). Arterial hypertension (P < 0.01) and neurological symptoms (P < 0.01) were significantly more frequent in the CSA-MP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P < 0.01) and lower platelet counts (P < 0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-MP patients on day 50 after BMT (P < 0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P < 0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.

Adult↗
PubMed1995

Heavy-chain immunoglobulin gene rearrangement and cytoplasmic immunoglobulin expression in acute monocytic leukemia following primary germ cell tumor.

A case of acute monocytic leukemia with rearrangement of the immunoglobulin heavy-chain gene and strong cytoplasmic immunoglobulin expression in a young patient treated with multi-drug chemotherapy for primary seminomatous germ cell tumor 13 months earlier is reported. The short latency period from the beginning of therapy for primary germ cell tumor and the abrupt onset of leukemia with no identifiable prodrome bear similarities to podophyllotoxin-related leukemias.

Adult↗
PubMed1994

Early detection of hematopoietic engraftment after bone marrow and peripheral blood stem cell transplantation by highly fluorescent reticulocyte counts.

At present, the appearance of neutrophils in the peripheral blood is considered to be the earliest sign of hematopoietic regeneration after myeloablative chemoradiotherapy. We studied erythroid regeneration in 27 allogeneic and 21 autologous marrow recipients using an automated reticulocyte counter employing a flow cytometric technique. Thereby, reticulocytes can be divided into a high, moderate and low fluorescent fraction according to RNA content. Marrow ablation caused an immediate and rapid fall in highly fluorescent reticulocytes (HFR) to zero in all patients. HFR reappeared after a median time of 7 days after allogeneic and 11 days after autologous marrow grafting. This was 7 and 2 days earlier than the appearance of first neutrophils. In allogeneic marrow recipients given erythropoetin after marrow infusion the median time to reach HFR of 0.2 and 0.5 x 10(9)/l was significantly shorter than time to reach similar absolute neutrophil counts (ANC). In allogeneic marrow recipients treated with G-CSF time to rise of HFR and ANC was almost exactly the same. Thus, automated flow cytometric reticulocyte counting allows early detection of hematopoietic regeneration and may be of clinical value for the early diagnosis of inadequate marrow function after marrow transplantation and the monitoring of erythroid regeneration under cytokine administration.

Adolescent↗
PubMed1993

Long-term survival and cure after marrow transplantation for congenital hypoplastic anaemia (Diamond-Blackfan syndrome).

Four patients with Diamond-Blackfan syndrome (congenital hypoplastic anaemia) whose disease was resistant to corticosteroid treatment and who were red blood cell transfusion-dependent, were given marrow grafts from allogeneic human-leucocyte-antigen (HLA)-identical siblings. The patients were conditioned with regimens including cyclophosphamide and busulfan. Three of four patients had sustained and complete marrow engraftment. One patient showed early signs of haematopoietic recovery but died on day 35 of pulmonary toxicity. The three surviving patients are well with normal haematopoiesis and Karnofsky performance scores of 100%, 3.0, 7.4 and 10.6 years after transplantation. Congenital hypoplastic anaemia can be treated successfully by allogeneic marrow grafts.

Acute Disease↗
PubMed1992

Specific growth inhibition of primitive hematopoietic progenitor cells mediated through monoclonal antibody binding to major histocompatibility class II molecules.

In a previous study using a canine model, we reported that a certain anti-class II monoclonal antibody (MoAb H81.9), which recognizes an epitope formed by the alpha and beta subunits of HLA-DR, prevented long-term engraftment of autologous marrow cells if administered intravenously during the first 4 days after 9.2 Gy of total body irradiation. Another MoAb (B1F6), reactive with only the beta subunit of HLA-DR and -DP, had no adverse effect on engraftment, although both MoAbs detect antigens on hematopoietic long-term repopulating cells as determined from complement-mediated lysis experiments. In the present study, continuous exposure of unfractionated human marrow to MoAb H81.9 specifically inhibited the growth of primitive progenitor cells that require multiple hematopoietic growth factors for proliferation (high proliferative potential colony forming cells [HPP-CFC] and burst-forming units-erythroid [BFU-e]), but had no effect on more mature, single factor responsive (CFU-GM), progenitor cells. In contrast, MoAb B1F6 did not impair primitive progenitor cell growth cultured as unfractionated marrow. However, when cell dose-response experiments were performed using CD34-positive cells plated at low cell densities, the marked inhibitory effects of MoAb H81.9 on HPP-CFC and BFU-e colony formation were not seen. These findings suggest that MoAb H81.9 may not inhibit primitive hematopoietic cells directly, but rather indirectly through the action of potent mediators derived from other HLA-DR-positive marrow cells.

Antibodies, Monoclonal↗
PubMed1992

Marrow transplantation for treatment of multisystem progressive Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) embraces disorders characterized by the presence of marrow-derived abnormal Langerhans cells. A small number of patients with multisystem disease, vital organ dysfunction and rapid disease progression are considered to have a poor prognosis despite various treatments. Antiproliferative and immunosuppressive therapy, in combination with marrow transplantation, could be the appropriate treatment for these poor-prognostic patients. Four patients with progressive LCH were treated with high dose chemotherapy and fractionated total body irradiation followed by either an allogeneic (n = 2) or autologous (n = 2) marrow graft. Two of them are alive and have been disease free for almost 2 and 4 years after marrow grafting, respectively. One of the two survivors is the recipient of an allogeneic and the other of an autologous marrow graft. Two patients died, one of intrapulmonary hemorrhage 14 days after transplantation with active disease at autopsy, and the other of relapse of the original disease 355 days after marrow grafting. For patients with multisystem progressive LCH, allogeneic and autologous marrow transplantation may offer an opportunity for long-term remission and disease-free survival.

Adolescent↗
PubMed1991

Late failure of autologous marrow grafts in lethally irradiated dogs given anti-class II monoclonal antibody.

We established a model of canine marrow autografts after 9.2 Gy total body irradiation (TBI) to study the role of class II antigens in hematopoietic stem cell growth and differentiation. Twenty dogs were given 9.2 Gy TBI, marrow, and intravenous (IV) murine anti-class II monoclonal antibody (MoAb). Infusion of 0.6 mg/kg/d of MoAb H81.98.21, an IgG2a reactive with HLA-DR, on days 0 to 4 after TBI did not prevent initial engraftment, but dogs died with late graft failure. MoAb B1F6, an IgG2a reactive with HLA-DR + DP, had no adverse effect on engraftment, although both MoAbs detect antigens on stem cells. The critical time for the effect of MoAbs is the first 4 days after transplantation. Our findings argue against several pathogenetic mechanisms, including removal of MoAb-coated stem cells by the reticuloendothelial system (RES), canine complement-mediated cytotoxic effects on stem cells, antibody-dependent cellular cytotoxicity, and inactivation of MoAb-coated cells by dog anti-mouse antibody. To distinguish between MoAb-induced damage to microenvironment (ME)/accessory cells (AC) and late graft failure from a lack of pluripotent stem cells, three dogs were given TBI, a marrow autograft, and MoAb H81.98.21 on days 0 to 4; one, given thoracic duct cells on day 6, developed graft failure; the other two, given marrow depleted of AC by L-leucyl L-leucine o-methyl ester (Leu-Leu-OMe), had sustained grafts. Findings support the notion that originally transplanted pluripotent stem cells are no longer present on day 6 and that the ME is functional and able to support newly injected stem cells.

Animals↗
PubMed1991

Characterization of a novel biochemical abnormality in galactosemia: deficiency of glycolipids containing galactose or N-acetylgalactosamine and accumulation of precursors in brain and lymphocytes.

Classic galactosemia, an inborn error of human galactose metabolism, is characterized by a deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT). The current model for the pathophysiology of this disease ascribes most of its symptoms to the toxicity of intracellular galactose-1-phosphate (Gal-1-P), one of the substrates of GALT which accumulates in the untreated disease state. Recently, a reduction in the intracellular concentration of UDP-Gal (uridine diphosphogalactose), one of the products of GALT, has been described in treated galactosemic patients. We investigated whether galactosemic patients might also have reduced amounts of those macromolecules that depend on UDP-Gal for their biosynthesis. We report a reduction in glycolipids that contain either galactose or its derivative N-acetylgalactosamine and an accumulation of the precursors to these compounds in the brain of a neonate with galactosemia. We also found an imbalance in glycolipids in galactosemic lymphoblasts. This novel biochemical abnormality observed in galactosemic patients is not addressed by dietary galactose-restriction therapy and could explain some of the chronic neurologic and other complications of galactosemia.

Acetylgalactosamine↗
PubMedDate not supplied

Symmetrical necrosis of globus pallidus with severe gait disturbance in a patient with myelodysplastic syndrome given allogeneic marrow transplantation.

A 21-year-old Caucasian man received an allogeneic marrow transplant (BMT) from his HLA-identical brother because of myelodysplastic syndrome. He remained red blood cell (RBC) transfusion dependent with persistent antibodies against the donor's RBC. Six months following BMT the patient suddenly developed a severe akinetic syndrome with gait disturbance and frequent falls and bilateral symmetrical lesions in basal ganglia. Concomitantly, micrococcus species septicemia from an infected Hickman catheter developed. Despite antimicrobial therapy and withdrawal of cyclosporin A, neurologic abnormalities persisted and were unresponsive to various therapies. Ischemic damage due to a vascular event during severe infection could be the most probable reason for the lesions seen in our patient, although infectious or toxic complications cannot be ruled out.

Adult↗
PubMedDate not supplied

Prospective monitoring of minimal residual disease in acute myeloid leukemia with inversion(16) by CBFbeta/MYH11 RT-PCR: implications for a monitoring schedule and for treatment decisions.

Minimal residual disease in patients with acute myeloid leukemia (AML) with inversion(16) can be monitored by CBFbeta/MYH11 RT-PCR. While the association between molecular remission (MR) in bone marrow (BM) and peripheral blood (PB) and long-term clinical remission (CR) seems to be established, there are insufficient data on the kinetics of CBFbeta/MYH11. We have performed a prospective study in order to generate a reasonable and sufficient schedule for PCR-monitoring. 11 patients with AML and inversion (16) in complete hematological remission have been prospectively monitored by CBFbeta/MYH11 RT-PCR in their BM and PB during an observation period of 7 to 67 months (median 32 months). Patients were followed during consolidation chemotherapy with repetitive cycles of high-dose Ara-C and after autologous or allogeneic stem cell transplantation in 2nd CR or refractory AML. MR never coincided with achievement of CR but occurred between 2 and 8 months after hematological remission. All patients in continuous CR were PCR-negative after 1-8 (median 4) months. Two patients relapsed despite MR for 10 to 15 months. Molecular relapse preceded hematological relapse by 3 to 5 months. Three out of four patients who were not in MR after 8 months relapsed. Allogeneic stem cell transplantation was able to eradicate minimal residual disease in 4/4 patients. In 2 patients a temporary reconversion to PCR-positivity was reversed by reduction of immunosuppression. 1 patient did not become PCR-negative until compete withdrawal of immunosuppression. We suggest that BM and PB should be examined after the last consolidation treatment. In case of MR, PB should be examined every 1 to 2 months and BM examination should be done only in case of PCR-positivity in PB in order to confirm the molecular relapse and to identify an impending cytogenetic and/or hematological relapse. CBFbeta/MYH11 RT-PCR monitoring is able to predict relapse 3 to 5 months prior to overt hematological relapse, offers a window of opportunity for preemptive therapy of molecular relapse and confers implications for immunotherapy in the setting of allografting.

Acute Disease↗