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J Treleaven

Publications and source records attributed to J Treleaven.

At least 55 records · Page 3Linked to original sources
PubMed1999

Long-term outcome of adult acute leukemia patients who are alive and well two years after allogeneic bone marrow transplantation from an HLA-identical sibling.

We studied the long-term outcome of 136 adults with acute leukemia (age 15-48 years at transplant, median 28; 112 myeloid, 22 lymphoblastic, 2 undifferentiated) who were alive in continuous remission two years after allografting from HLA-identical sibling donors. Six relapsed 25-46 months (median 30) after BMT. Fourteen (10%) died of non-relapse causes (12 transplant-related and 2 unrelated) 24-140 months (median 73) after BMT; mainly due to complications of chronic GVHD (8 infections, 3 secondary malignancies). One hundred and seventeen (86%) patients are alive in remission 25-226 months (median 103) after BMT; 116 (85%) in continuous remission. Eight survivors have symptomatic chronic GVHD requiring therapy (Karnofsky scores 60-90%, median 80%). The majority of those without chronic GVHD have Karnofsky scores of 100%. The 10-year probabilities of survival, toxic death, and relapse (from the 2-year mark) are 81%, 13%, and 5%. Twenty-two (19%) survivors had creatinine levels of > 110 mumol/L (one more than double), and 11 (9%) had bilirubin levels of > 17 mmol/L (one more than double) at the last follow-up. The absence of chronic GVHD at the 2-year mark (RR 3.5, P = .004), and female sex (RR 2.9, P = .04) influenced overall survival favorably, and the absence of chronic GVHD at the 2-year mark (RR 8.1, P = .001) influenced toxic death favorably. We conclude that patients with acute leukemia who are alive and well without chronic GVHD two years following an allograft have a high probability of being cured, whereas patients with active chronic GVHD requiring immunosuppression continue to be at risk of non-relapse death. The incidence of long-term liver and kidney dysfunction measured by serum bilirubin and creatinine is low.

Acute Disease↗
PubMed1999

Long-term follow-up of relapsed acute leukemia treated with immunotherapy after allogeneic transplantation: the inseparability of graft-versus-host disease and graft-versus-leukemia, and the problem of extramedullary relapse.

Long-term outcome of 23 acute myeloid (AML, n=16) or lymphoblastic (ALL, n=7) leukemia patients who had received immunotherapy for treatment of persistent or recurrent disease 1.5-26 (median 4) months after allogeneic transplantation was studied to determine eventual survival. Immune manipulation comprised donor leukocyte infusion (n=18), interferon-alpha2b and/or interleukin-2 (n=15), and cyclosporine withdrawal (n=11) in various combinations. Graft-versus-host disease (GVHD) developed in 12 patients. Thirteen of 20 evaluable patients responded; 6 relapsing again. Eight patients died of toxicity, and 10 of progressive disease at 3-206 weeks (median 11). Five patients (3 AML, 2 ALL) are alive in remission with GVHD 2-46 months (median 23) after immunotherapy with Karnofsky scores of 70-100% (median 80). The overall survival of the whole group is 1-206 weeks (median 12), with an actuarial survival of 22% at 2 years. The development of GVHD was associated with superior survival in multivariate analysis (P=.007). Seven patients received immunosuppression because of the severity of GVHD (grade III/IV acute or extensive chronic): 3 died of GVHD, 3 improved but relapsed concomitantly, and 1 is alive in remission with extensive chronic GVHD. Four episodes of extramedullary relapse (granulocytic sarcomas) were seen in 3 patients with AML whose marrow remained in remission. We conclude that GVHD appears to be inseparable from graft-versus-leukemia in relapsed acute leukemia patients undergoing immunotherapy with a high proportion of patients dying due to toxicity or progressive disease, and isolated extramedullary relapse seems to be unusually common.

Acute Disease↗
PubMed1999

The impact of karyotype on remission rates in adult patients with de novo acute myeloid leukemia receiving high-dose cytarabine-based induction chemotherapy.

One hundred and twenty-eight patients aged 15 years or over (median 34) with de novo acute myeloid leukemia (AML) received 2- or 3-drug induction chemotherapy comprising 5 days of daily high-dose cytarabine (2 g/m2 q12h) and etoposide (100 mg/m2), without (n=62, 1985-90, protocol BF11) or with (n=66, 1990-97, protocol BF12) daily 5 mg/m2 anthracycline (61 idarubicin, 5 mitoxantrone). Twelve patients with t(15;17) were not included. Evaluable karyotypes were obtained in 110 (86%): 30 (27%) favorable, 60 (55%) intermediate, and 20 (18%) adverse. Three patients dying during chemotherapy were inevaluable. Eighty-four (67%) patients remitted with one cycle, and the overall complete remission (CR) rate was 72%. CR rates were comparable for patients with and without evaluable karyotypes. CR rates with BF11 (64% after one cycle; 72% overall) and BF12 (70% after one cycle; 72% overall) were comparable (P=.4 and 1.0 respectively). CR rates after one cycle (86%, 61% and 55%; P=.03) as well as overall CR rates (90%, 69% and 55%; P=.02) were significantly different for patients with favorable, intermediate and adverse karyotypes respectively. In Cox analysis, the karyotype was the only factor found to influence CR independently. We conclude that the karyotype of the leukemic clone is the most important determinant of response to high-dose cytarabine-based induction chemotherapy in AML. The addition of idarubicin to high-dose cytarabine and etoposide does not appear to improve CR rates. A different treatment strategy may be needed to improve CR rates for patients with non-favorable karyotypes.

Acute Disease↗
PubMed1999

Metastatic extramedullary plasmacytoma of the lung.

Extramedullary plasmacytomas (EMP) comprise 4% of all plasma cell neoplasms and commonly in the upper airway or digestive tract but rarely develop in the lungs. We present a case of primary pulmonary plasmacytoma in an 89 year old man, presented as a hilar mass with associated intrathoracic and extrathoracic lymph node metastases, but without evidence of myeloma. Treatment options for EMP include surgery, surgery and radiotherapy, surgery and chemotherapy or chemotherapy alone. Local recurrence rate is reported as 10-30%, with 17-48% progressing to multiple myeloma and median survival being 63-101 months. In view of the advanced age of this patient, who was initially treated unsuccessfully with intravenous cyclophosphamide and subsequently with two cycles of VAMP chemotherapy with good resolution of his disease, he is undergoing regular follow-up only.

Aged↗
PubMed1998

Identification of patients who may benefit from prophylactic immunotherapy after bone marrow transplantation for acute myeloid leukemia on the basis of lymphocyte recovery early after transplantation.

Two hundred and one patients (median age, 29 years) with acute myeloid leukemia (AML) underwent bone marrow transplantation (BMT) from HLA-identical sibling donors after conditioning with melphalan-total-body irradiation (TBI) (57%), cyclophosphamide-TBI (35%), or chemotherapy alone (8%). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine alone (68%), cyclosporine-methotrexate (26%), or T-cell depletion (6%). The probability of relapse was calculated as a function of the absolute lymphocyte count (10(9)/L) on days 27 to 30 posttransplant (<0.1 v >/=0.1, <0.2 v >/=0.2, and <0.3 v >/=0.3). In each of these 12 comparisons, the probability of relapse was higher for the group with the lower lymphocyte count. Because the difference was most significant (P = .004) for an absolute lymphocyte count of <0.2 on day 29 (3-year relapse probability, 42%) versus >/= 0.2 (16%), this variable was included in a Cox model to determine factors independently affecting relapse. Multivariate analysis showed that conditioning regimens other than melphalan-TBI, a low lymphocyte count on day 29, French-American-British (FAB) subtypes M4-7, and a nucleated cell dose of > 2.42 x 10(8)/kg was associated with a higher risk of relapse. We conclude that slow lymphocyte recovery after allogeneic BMT, to < 0.2 x 10(9)/L 29 days in this analysis, appears to be associated with a higher risk of relapse in patients with AML. This group of patients may benefit from posttransplant immune manipulations such as abbreviated GVHD prophylaxis, or donor cell or cytokine administration to enhance graft-versus-leukemia reactions to reduce relapse.

Acute Disease↗
PubMed1998

The importance of CD34+/CD33- cells in platelet engraftment after intensive therapy for cancer patients given peripheral blood stem cell rescue.

The study was designed to determine whether the number of CD34+/CD33- cells given at autologous peripheral blood stem cell (PBSC) rescue after intensive therapy for cancer was a better predictor of platelet engraftment than the total number of CD34+ cells infused. Comparison between the total number of CD34+ cells/kg infused with the number of CD34+/CD33- cells/kg infused showed that, generally, 2 x 10(6) total CD34+ cells contained 1.38 x 10(6) CD34+/CD33- cells. There was poor correlation between the number of CD34+/CD33- and CD34+/CD33+ cells in the graft (r = 0.332). Engraftment times for platelets and neutrophils were evaluated in 68 patients. There was no significant difference between the times for platelets to reach >25 x 10(9)/l or neutrophils to reach >0.5 x 10(9)/l among patients who received > or <2 x 10(6) total CD34+ cells or > or <1.38 x 10(6) CD34+/CD33- cells although the latter was consistently the better predictor. Platelet recovery to >50 x 10(9)/l and >100 x 10(9)/l was delayed significantly in patients who received <1.38 x 10(6) CD34+/CD33-/kg infused (P < 0.02 and P < 0.05, respectively). The number of CD34+/CD33- cells/kg infused was a stronger predictor of platelet recovery than the total number of CD34+ cells infused (P < 0.05 for platelets >50 or >100 x 10(9)/l). Although platelet recovery was delayed significantly in patients who had <4 x 10(4) granulocyte-macrophage colony-forming units (CFU-GM)/kg infused, the time delay between receipt of PBSCs and availability of the colony counts limits the use of this assay to patients who do not require stem cells to be given immediately. Our data suggest that the number of CD34+/CD33- cells given at PBSC rescue provide information about the quality of the graft necessary for long-term platelet engraftment. However, since the percentage of CD34+/CD33- cells shows considerable inter-patient variation, measurement of this cell population may be important in patients who experience poor stem cell mobilization or when a target dose of 2 x 10(6) total CD34+ cells/kg is not achieved.

Adolescent↗
PubMed1998

Red cell fragmentation (schistocytosis) after bone marrow transplantation.

Red cell fragmentation is often the earliest sign of thrombotic microangiopathy. Days +14, +28 and +42 blood films from 58 allograft and 32 autograft recipients were reviewed blind to determine the incidence and severity of schistocytosis (the number of fragmented red cells per 1000 red cells expressed as a percentage). Schistocytosis was graded as mild (<1%), moderate (1-1.9%) or severe (> or =2%). Schistocytes were seen in 99% of day 14 films (0.1-3.0%, median 0.4%), 97% of day 28 films (0.1-3.2%, median 0.4%), and 98% of day 42 films (0.1-4.3%, median 0.5%). Nine patients (10%) had severe fragmentation and 20 patients (22%) had moderate fragmentation at some time or the other. The difference in the extent of fragmentation between the days was not significant. Allogeneic BMT was associated with more extensive fragmentation than autologous transplantation on day 28 (P = 0.008) and day 42 (P = 0.02). Age, conditioning regimen and diagnosis had no influence. None of the patients followed-up for 6 months after transplant developed full-blown thrombotic microangiopathy. The occasional patient showing mild clinical and laboratory features of hemolysis responded well to adjustment of fluid balance and cyclosporine dose where applicable. Our data indicate that mild red cell fragmentation is a common morphologic finding after transplantation with no clinical significance in the absence of other clinical and laboratory findings suggestive of thrombotic microangiopathy, although patients with moderate or severe fragmentation should be monitored closely.

Adolescent↗
PubMed1998

Familial acute myeloid leukaemia: four male members of a single family over three consecutive generations exhibiting anticipation.

A kindred with familial acute myeloid leukaemia (AML) is described displaying the concept of anticipation which refers to increased disease severity and/or earlier age at onset with succeeding generations. The affected individual in the first generation was the father (aged 34 years at diagnosis) of two affected members of a single sibship (aged 24 and 25 years). The fourth patient is the son (aged 4 years) of one of these brothers in the second generation. The AML was of different subtypes and a karyotypic abnormality (del[6q]) was detected in one of three patients. The first-generation patient died during chemotherapy; the remaining three patients are in complete remission after chemotherapy and autologous bone marrow transplantation.

Acute Disease↗
PubMed1998

A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results.

High-dose chemotherapy (melphalan) with autologous marrow stem cell support (AMSCS) results in high response rates in multiple myeloma (MM), with up to 50% of patients achieving complete remission. However, these remissions are generally not durable. As the cytokine interferon alpha has been shown to prolong partial response following conventional chemotherapy, this trial was conducted to evaluate its role following high-dose chemotherapy. 85 patients were randomly assigned to maintenance treatment with interferon alpha, 3 x 10(6) units/m2 subcutaneously three times weekly until relapse or no further treatment following recovery from high-dose chemotherapy (melphalan 140-200 mg/m2 or busulphan 16 mg/kg) combined with AMSCS. At 5.8 years following the accrual of the last patient in this trial, 38 patients had died, 17 in the interferon arm and 21 in the control arm. The median progression-free survival (PFS) in the 42 patients randomized to interferon alpha was 46 months versus 27 months in the controls. Both overall survival and PFS, which were highly significant at median follow-up of 52 months, have now ceased to be significant, because most patients have ultimately succumbed to their disease. Interferon was tolerated by the majority of patients with very good compliance. Toxicity consisted mainly of flu-like symptoms and malaise which were usually self-limiting. The results of such a pilot study should be carefully interpreted and the benefits of interferon should be confirmed in larger multicentre studies in the setting of minimal residual disease following autologous transplantation.

Adult↗
PubMed1997

Prospective, concurrent comparison of the Cobe Spectra and Haemonetics MCS-3P cell separators for leukapheresis after high-dose filgrastim in patients with hematologic malignancies.

A prospective study was undertaken to compare the mononuclear cell, CD34+ cell, and CFU-GM yields of the Haemonetics MCS-3P and the Cobe Spectra cell separators in ten patients (nine multiple myeloma and one non-Hodgkin lymphoma) on two consecutive days after mobilization with high-dose filgrastim (12-16 micrograms/k) for 4 days. All patients were harvested once on each machine, five starting on each machine. The target duration of the procedure on the Spectra was 160 minutes, and the target blood volume processed on the MCS-3P was 60-70 ml/kg body weight. Both machines were operating on the 1995 software versions supplied by the respective manufacturers. The time taken for the procedure was significantly longer with the Haemonetics machine. The volumes of blood processed and the product collected were significantly higher with the Spectra, as were the absolute mononuclear and CD34+ cell yields, and yields per unit time. Mononuclear and CD34+ cell yields per unit volume of blood processed were comparable for both machines. The differences in CFU-GM yields were not significant, largely because of wide interpatient variations. The extent of platelet depletion as a result of the procedure was greater with the Spectra because of the higher blood volume being processed. We conclude that the Cobe Spectra is a significantly faster machine than the Haemonetics MCS-3P; and consequently, its use is associated with higher mononuclear and CD34+ cell yields.

Antigens, CD34↗
PubMed1997

Comparison of marrow vs blood-derived stem cells for autografting in previously untreated multiple myeloma.

Sixty-three new untreated patients with multiple myeloma under the age of 70 years received C-VAMP induction treatment followed by high-dose intravenous melphalan (200 mg m(-2)) and autologous stem cell transplant, either with marrow [autologous bone marrow transplants (ABMT), n = 26] or with granulocyte colony-stimulating factor (G-CSF)-mobilized stem cells from the blood [peripheral blood stem cell transplants (PBSCT), n = 37]. This was a sequential study and the two groups were not significantly different for all known prognostic variables. The complete remission (CR) rate after high-dose treatment was the same for both groups [ABMT 84% and PBSCT 70%; P = not significant (NS)]. Neutrophil recovery to 0.5 x 10(9) l(-1) occurred at a median of 22 days in the ABMT patients compared with 19 days for the PBSCT patients (P = NS). Platelet recovery to 50 x 10(9) l(-1) was significantly faster in PBSCT patients (19 days vs 33 days; P = 0.0015), and the PBSCT patients spent fewer days in hospital (median 20 vs 27 days; P = 0.00001). There was no difference in the two groups with respect to starting interferon (58 days for ABMT vs 55 days for PBSCT), and tolerance to interferon was identical. The median overall survival (OS) and progression-free survival (PFS) for the PBSCT patients has not yet been reached. The OS in the ABMT patients at 3 years was 76.9% (95% CI 60-93%) compared with 85.3% (95% CI 72-99%) in the PBSCT patients (P = NS), and the PFS at 3 years in the ABMT patients was 53.8% (95% CI 34-73%) and in the PBSCT patients was 57.6% (95% CI 34-81%) (P = NS). The probability of relapse at 3 years was 42.3% in the ABMT arm compared with 40% in the PBSCT patients (P = NS). Thus, PBSCT patients had a faster engraftment and a shorter stay in hospital than ABMT; the survival outcome and probability of relapse was the same for both groups.

Adult↗
PubMed1997

Early identification of patients at risk of death due to infections, hemorrhage, or graft failure after allogeneic bone marrow transplantation on the basis of the leukocyte counts.

Allograft recipients are often unwell with significant organ dysfunction by the time delayed or failed engraftment is diagnosed. We attempted to identify factors associated with graft failure, or death due to infection, hemorrhage or graft failure in 712 patients undergoing allogeneic BMT. Low leukocyte counts between days 12 and 22 were strongly associated with subsequent graft failure or death. In multivariate analysis, a leukocyte count of < or = 0.2 x 10(9)/l on day 16 was the most powerful predictor of graft failure or death. Transplants from HLA-mismatched and unrelated donors were also associated with increased risk of both, and T cell depletion with increased risk of graft failure. On the basis of these findings, it may be possible to define graft failure in functional terms as early as 2 weeks after BMT rather than at 3 or 4 weeks. The use of growth factors can then be limited to patients most likely to benefit from them, and it may be possible to salvage patients at risk of complications of low counts early before their clinical condition deteriorates. We suggest that patients with leukocyte counts of 0.2 x 10(9)/l or less 14-16 days after BMT should be started on G-CSF or GM-CSF even if they are clinically well, and consideration should be given to a second infusion of cells.

Adolescent↗
PubMed1997

Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy.

We studied 231 acute leukemia patients relapsing after allogeneic (n = 114) or autologous (n = 117) BMT to assess the outcome of further therapy. In general, all patients in good condition were eligible for second transplants except for post-allograft relapses from 1993-1994 onwards who received cytokine- or cell-mediated immunotherapy. The major reason for patients not progressing to second graft was death from progressive disease or toxicity of salvage chemotherapy. Seventeen of 231 patients (7%) were alive at the last follow-up. Six of 14 post-autograft relapses treated with second transplants were alive and well, compared with five of 103 not undergoing second grafts (P < 0.0001). One of 23 post-allograft recipients treated with second allografts was alive with an extramedullary relapse, compared with five of 13 receiving immunotherapy and none of 78 receiving standard-dose or palliative therapy (P < 0.0001). We conclude that only a small proportion of highly selected acute leukemia patients relapsing after a transplant reach the stage of a conventional second transplant. In our experience, second allografts after myeloablative therapy in patients relapsing after one allograft are associated with very poor results, and immunotherapy may be a better approach in such cases. Selected patients relapsing after an autograft may become long-term survivors following a second autograft or an allograft.

Acute Disease↗
PubMed1997

Sensitivity of secondary acute myeloid leukemia relapsing after allogeneic bone marrow transplantation to immunotherapy with interferon-alpha 2b.

A patient with acute myeloid leukemia secondary to therapy of choriocarcinoma underwent T cell non-depleted allogeneic bone marrow transplantation from an unrelated donor in first untreated relapse. Persistent/relapsed leukemia 4 months after transplantation did not respond to cessation of cyclosporine. Due to logistic difficulties in obtaining donor leukocytes, she was treated with interleukin-2 and interferon-alpha 2b. Although the interleukin could be administered for a short period only, the interferon was continued for 4 months. Interferon was stopped when limited chronic graft-versus-host disease developed, but was followed by extramedullary and early marrow relapse. Reinstitution of interferon resulted in the development of scleroderma-like extensive chronic GVHD and remission. Interferon was given for 5 months. GVHD improved slowly with treatment, but scleroderma-like changes still persist. The patient is alive with no evidence of disease and a Karnofsky score of 90% 41 months after relapse and 26 months after stopping cyclosporine. We conclude that cytokines alone may occasionally result in a durable response of acute leukemia relapsing after allografting, and should be considered in patients with a low tumor burden if it is difficult to obtain donor cells.

Adult↗
PubMed1997

Amphotericin B lipid complex (ABLC) for the treatment of confirmed or presumed fungal infections in immunocompromised patients with hematologic malignancies.

Sixty-four adult patients (median age 43) with hematologic malignancies who were immunocompromised after allogeneic (n = 23) or autologous (n = 9) blood/marrow transplantation, or chemotherapy (n = 32) received 68 courses of amphotericin B lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed (n = 52) or proven (n = 16) fungal infection. The major indications for ABLC were failure of previous antifungal therapy and/or renal dysfunction. Fifty-three treatment courses in 49 patients comprising 4-58 doses (median 10) were considered evaluable. Fourteen courses administered for confirmed infections resulted in nine complete and one partial responses, and four failures (71% response). Thirty-nine empiric courses resulted in 18 complete and six partial responses, and 14 failures (64% response). The overall response rate was 66%. Five of seven evaluable patients with aspergillus pneumonia responded. Response rates were comparable for chemotherapy, autograft and allograft recipients. The change in serum creatinine from the beginning to the end of therapy was -284 to +277 mumol/l (median +24). The creatinine doubled during seven evaluable courses of therapy, five of which were associated with concomitant nephrotoxic therapy. Nephrotoxicity was comparable for transplant and chemotherapy patients. Renal dysfunction necessitated discontinuation of ABLC in only four patients. These data suggest that ABLC is effective in presumed or confirmed fungal infections in immunocompromised patients after transplantation or chemotherapy.

Adolescent↗