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Biomedical subjects

J Meharchand

Publications and source records attributed to J Meharchand.

At least 19 recordsLinked to original sources
PubMed2003

Busulfan and cyclophosphamide as a preparative regimen for allogeneic blood and marrow transplantation in patients with non-Hodgkin's lymphoma.

This study reports on overall and recurrence-free survival (OS and RFS) of 37 consecutive patients with low- and intermediate-grade NHL receiving a related donor allogeneic BMT using a nonradiation-containing preparative regimen. In addition, transplant-related toxicity and factors influencing outcome are discussed. The preparative regimen consisted of busulfan and cyclophosphamide. Median patient age was 44 years (range 20-55). In all, 18 were female. Median follow-up of surviving patients from BMT was 4.2 years. A total of 25 patients had low-grade, and 12 intermediate grade NHL. Most patients (89%) were treated with at least two different chemotherapy regimens prior to BMT. In all, 22 patients (59%) were transplanted in partial remission, 15 (41%) in complete remission. OS at 12 months was 89% (95% confidence interval (CI) of 79-99%) and 79% (64-93%) at 60 months. RFS at 12 months was 86% (75-97%) and at 5 years 70% (54-86%). Four patients (11%) relapsed. Seven patients (19%) died, six because of treatment-related toxicity and one with relapse. Univariate analysis showed improved OS for younger patients and patients of female gender, suggesting that allogeneic BMT using busulfan-cyclophosphamide as a preparative regimen can achieve disease control and possibly cure patients with NHL particularly younger ones.

Adult↗
PubMed2000

Bone marrow mobilized with granulocyte colony-stimulating factor in related allogeneic transplant recipients: a study of 29 patients.

We studied whether a short course of granulocyte colony-stimulating factor (G-CSF) administered to normal donors immediately before bone marrow (BM) harvest would shorten time to neutrophil and platelet engraftment in matched related allogeneic BM recipients. Twenty-nine normal donors received 4 consecutive daily subcutaneous injections of G-CSF (median dose, 12.1 microg/kg per day; range, 9.6-15.7 microg/kg per day) immediately before BM harvest. Donors tolerated G-CSF well, with only mild myalgias and arthralgias, and BM was easy to aspirate. The BM harvest contained a median of 5.3 x 10(8) white blood cells (WBCs)/kg (range, 3.1-11.1 x 10(8) WBCs/kg) and 2.5 x 10(6) CD34+ cells per kg (range, 1.5-7.3 x 10(6) CD34+ cells per kg). Median times to neutrophil (18 days [range, 11-30 days] versus 22 days [range, 16-36 days]; P = .05) and platelet (22 days [range, 15-55 days] versus 27 days [range, 18-46 days]; P = .04) engraftment were statistically shorter than those of historical control subjects whose donors had not received G-CSF before BM harvest. However, secondary engraftment-dependent outcomes including red blood cell and platelet transfusions, febrile days, days on antibiotics, days from transplant to hospital discharge, and days in hospital during the first 60 days after transplant were not statistically different from historical control subjects. We conclude that G-CSF administered to normal donors immediately before harvest facilitates BM aspiration, increases the WBC content of the harvest, and hastens neutrophil and platelet engraftment compared with historical control subjects.

Adolescent↗
PubMed2000

Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network, Canada.

In 1986, the bone marrow transplant centers in Ontario agreed to a strategy for the treatment of patients with NHL. Suitable patients would undergo autotransplant but be referred for allotransplant if they had persistent marrow involvement or an inadequate marrow/stem cell harvest. Data of all patients were recorded in a database. We reviewed this database to compare these transplant modalities with respect to overall survival, rate of relapse and treatment-related mortality. Between January 1986 and August 1997, 429 patients underwent BMT for NHL - 385 autotransplants and 44 allotransplants. Sixty-eight percent of patients received their transplant for aggressive NHL, while the others had indolent lymphoma. Three-year actuarial survival did not differ between allogeneic and autologous BMT: 71% vs 62%, respectively (P = 0.5330 by log-rank testing). Three-year actuarial rate of relapse was lower after allotransplant than autotransplant: 6% vs 41%, respectively (P = 0.0006 by log-rank testing). Treatment-related mortality was higher after allotransplant than autotransplant: 23% vs 6%, respectively (P = 0.001 by chi2 analysis). For further comparison, autotransplant patients were randomly matched 2:1 with the allotransplant patients for age +/- 5 years, disease status at BMT, disease histology, and year of BMT. In the matched comparison, survival did not differ (relative risk of death after allotransplant: 0.711 (95% CI: 0.309-1.637)). Relapse rate was significantly lower in the allotransplant group (relative risk of relapse for allotransplant: 0.190 (95% CI: 0.043-0.834)) and treatment-related mortality was not significantly different (relative risk for allotransplant: 1.425 (95% CI: 0.527-3.851)). In conclusion, a review of a provincial strategy for treatment of NHL, shows that survival is not different after allogeneic or autologous BMT, but the rate of relapse is lower after allotransplant. These data support continuing the current provincial strategy.

Adolescent↗
PubMed2000

Effect of premedication guidelines and leukoreduction on the rate of febrile nonhaemolytic platelet transfusion reactions.

Platelet transfusion reactions were prospectively studied in haematology/oncology patients at five university teaching hospitals over three consecutive summers. The initial summer study provided baseline information on the use of premedications and the rate of platelet transfusion reactions (fever, chills, rigors and hives). Most (73%) platelet recipients were premedicated and 30% (95% CI 28-33%) of transfusions were complicated by reactions. The second study followed implementation of guidelines for premedicating platelet transfusions. Despite a marked reduction in premedication (50%), there was little change in the platelet transfusion reaction rate, 26% (95% CI 24-29%), or the type of reactions. The third study followed implementation of prestorage platelet leukoreduction while maintaining the premedication guidelines. The reaction rate decreased to 19% (95% CI 17-22%). For nonleukoreduced platelets, there was a statistically significant association between the platelet age and reaction rate (P = 0.04). For leukoreduced platelets, there was no statistically significant association between platelet age and reaction rate (P = 0.5). Plasma reduction of nonleukoreduced platelet products also reduced the reaction rate. These prospective studies document a high rate of platelet transfusion reactions in haematology/oncology patients and indicate premedication use can be reduced without increasing the reaction rate. Prestorage leukoreduction and/or plasma reduction of platelet products reduces but does not eliminate febrile nonhemolytic platelet transfusion reactions.

Blood Preservation↗
PubMed1999

Secondary acute myeloid leukemia 4 years after the diagnosis of hairy cell leukemia: case report and review of the literature.

A 49-year-old man diagnosed with hairy cell leukemia (HCL) achieved a complete remission lasting 4 years after treatment with cladrabine and subsequently developed acute myeloid leukemia. Although a wide variety of second malignancies have been noted in HCL with an incidence of 8.7%, acute myeloid leukemia (AML) has been reported only once previously in a splenectomized patient who had been treated with alpha interferon.

Acute Disease↗
PubMed1999

Management of allogeneic bone marrow transplant recipients at risk for cytomegalovirus disease using a surveillance bronchoscopy and prolonged pre-emptive ganciclovir therapy.

BACKGROUND: Patients undergoing allogeneic bone marrow transplant (BMT) are considered to be at increased risk of cytomegalovirus (CMV) disease if they and/or their donor are CMV seropositive pre-transplant. Although several pre-emptive strategies have been shown to be effective in preventing early CMV disease, the ability of pre-emptive strategies using prolonged ganciclovir therapy to reduce the incidence of late-onset CMV infection, disease and mortality has not been fully evaluated. OBJECTIVE: To assess the efficacy of 18 weeks of pre-emptive ganciclovir therapy in preventing late-onset (> 100 days post-transplant) CMV disease when administered to asymptomatic BMT patients found to have CMV in bronchoalveolar lavage (BAL) fluid obtained during a surveillance bronchoscopy approximately 35 days post-transplant. To determine whether or not survival of BMT recipients is influenced by pre-transplant donor and recipient CMV serostatus in the context of this pre-emptive ganciclovir strategy. STUDY DESIGN: Consecutive patients undergoing allogeneic BMT were assessed for their risk of developing CMV disease based on their pre-transplant CMV serostatus and that of their donor. Patients who were CMV seropositive and/or received marrow from a CMV seropositive donor underwent a surveillance bronchoscopy and BAL approximately 35 days post-transplant. Patients with positive BAL fluid for CMV received pre-emptive ganciclovir therapy for 18 weeks at decreasing dose levels. Patients considered to be at low risk for the development of CMV disease (donor and recipient CMV seronegative) were followed without intervention. RESULTS: Of 98 consecutive patients, 55 were considered to be at risk for CMV disease and underwent a surveillance bronchoscopy. Sixteen (29%) patients had a positive BAL fluid for CMV and were started on pre-emptive ganciclovir therapy. Two patients progressed and died with CMV-related pneumonia. One additional patient developed CMV-related enteritis on day 42 post-transplant and recovered with continuing ganciclovir treatment. Of the 39 patients with a negative BAL fluid for CMV, one developed a fatal CMV pneumonia 150 days post-transplant and two additional patients developed gastrointestinal CMV disease 28 and 57 days post-BMT, respectively. None of the patients in the low risk group developed CMV disease. CONCLUSIONS: The strategy utilizing a surveillance bronchoscopy for CMV and initiating prolonged (18 weeks) pre-emptive ganciclovir therapy for patients with a positive BAL fluid for CMV resulted in a low incidence of CMV-related post-transplant complications. After a minimum follow-up of 16 months, late CMV reactivations (occurring > 100 days post-transplant) were not observed in the group of individuals pre-emptively treated with ganciclovir. This observation suggests that prolonged therapy with a reduced dose of ganciclovir may be important in the prevention of CMV reactivation. The CMV serostatus of donors and recipients prior to BMT did not correlate with survival.

Adult↗
PubMed1999

The clinical utility of CMV surveillance cultures and antigenemia following bone marrow transplantation.

At our institution, the cytomegalovirus (CMV) prophylaxis protocol for allogeneic bone marrow transplant (BMT) recipients who are CMV-seropositive or receive marrow from a CMV-seropositive donor consists of a surveillance bronchoscopy approximately 35 days posttransplant. Patients with a positive surveillance bronchoscopy for CMV receive pre-emptive ganciclovir. In order to determine the utility of other screening methods for CMV, we prospectively performed weekly CMV antigenemia, and blood, urine and throat cultures from time of engraftment to day 120 post-BMT in 126 consecutive patients. Pre-emptive ganciclovir was given to 11/81 patients (13.6%) because of a positive surveillance bronchoscopy for CMV. Results of CMV blood, urine and throat cultures and the antigenemia assay done prior to or at the time of the surveillance bronchoscopy were analyzed for their ability to predict the bronchoscopy result. The antigenemia test had the highest positive and negative predictive values (72% and 96%, respectively). The ability of these tests to predict CMV disease was evaluated in the 70 patients with a negative surveillance bronchoscopy who did not receive pre-emptive ganciclovir. Of 19 cases of active CMV disease, CMV antigenemia was positive in 15 patients (79%) a mean of 34 days preceding symptoms. Blood cultures were positive in 14/19 patients (74%) a mean of 31 days before onset of disease. CMV antigenemia is useful for predicting the surveillance bronchoscopy result, and also predicts the development of CMV disease in the majority of patients missed by the surveillance bronchoscopy.

Adolescent↗
PubMed1999

Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma.

Randomized trials conducted by the Intergroupe Française du Myelome (IFM) demonstrate that the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT) improves event-free (EFS) and overall survival (OS) in younger patients with multiple myeloma (MM). Nevertheless, current HDCT regimens remain inadequate as all patients ultimately relapse following SCT. In an attempt to improve the OS of MM patients post-SCT we used an escalated HDCT regimen incorporating both intensified melphalan (160 mg/m2) and fractionated total body irradiation (12 Gy) to maximize the dose response of myeloma cells to these agents and included infusional etoposide 60 mg/kg in an attempt to eradicate clonal B cells potentially contributing to the myeloma clone. One hundred patients with MM received this intensified SCT regimen. The 100-day treatment-related mortality was 12% predominantly reflecting the development of interstitial pneumonitis (IP) in 28% of patients of whom 7/28 (25%) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60% and 35%, respectively. The median OS from the time of transplant is 41 months and the median EFS is 28 months. More than two prior chemotherapy regimens, previous radiation therapy (RT) and the presence of an abnormal karyotype involving chromosomes 11 or 13 were significantly predictive of poor outcome. Interferon maintenance was not associated with improved outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens.

Adult↗
PubMed1998

Safety of therapeutic anticoagulation in patients with multiple myeloma receiving autologous stem cell transplantation.

The use of autologous stem cell transplantation (ASCT) for the treatment of multiple myeloma is increasing. Anticoagulation may be required during ASCT for conditions such as Hickman line thrombosis. The safety of anticoagulation in patients receiving ASCT is unknown. We report a retrospective case-control study of the safety of therapeutic anticoagulation in patients with multiple myeloma receiving ASCT. We identified 10 patients who received therapeutic anticoagulation during ASCT. For each of the 10 cases identified, two matched controls were selected. As a primary endpoint, bleeding complications were assessed. Secondary endpoints included survival, length of hospital stay, transfusion requirements, grade 4 toxicity, and days to platelet engraftment. Bleeding complications were not significantly different between patients receiving anticoagulation and controls (P = 0.3). Three of 10 anticoagulated patients and two of 20 controls had a bleeding complication. Mortality during admission was similar (P = 1.0); one anticoagulated patient and one control died of sepsis. A trend towards increased median number of platelet transfusions in the heparinized patients was seen (27 vs 12 units, P = 0.055), reflecting the higher transfusion threshold chosen for the anticoagulated patients. The other secondary endpoints did not differ between patients and controls. In this case control study, bleeding was not significantly increased in the group receiving anticoagulation during ASCT. This group electively received more units of platelets than controls. Thus, therapeutic anticoagulation can be managed with minimal increased toxicity during ASCT.

Adult↗
PubMed1998

Clinical and economic analysis of allogeneic peripheral blood progenitor cell transplants: a Canadian perspective.

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↗
PubMed1998

Effect of cytomegalovirus infection on 1-year mortality rates among recipients of allogeneic bone marrow transplants.

The effect of cytomegalovirus (CMV) infection on 1-year mortality rates among allogeneic bone marrow transplant recipients who are receiving a standard protocol as prophylaxis for CMV infection is unclear. We determined the risk factors for death within 1 year among 103 bone marrow transplant recipients by performing a multivariate analysis. The results of donor and recipient CMV serologies did not predict 1-year mortality, although there was a trend towards higher mortality among CMV-seropositive recipients who received marrow from seronegative donors (P = .077). Multivariate analysis revealed that the factors independently associated with 1-year mortality were the development of CMV antigenemia (relative risk [RR] = 2.74; confidence interval [CI] = 1.28-5.86), bone marrow transplantation (BMT) from unrelated donors (RR = 3.20; CI = 1.30-7.92), and severe acute graft-versus-host disease (RR = 3.50; CI = 1.50-8.17). Although significant on univariate analysis, advanced underlying disease before BMT and the development of active CMV disease after BMT were not independent risk factors. In conclusion, the development of CMV antigenemia after BMT was associated with increased 1-year mortality, while the development of active CMV disease was not. Reactivation of CMV infection may represent a marker of poor immune reconstitution or may contribute to further immunosuppression after BMT.

Adolescent↗
PubMed1998

Testicular plasmacytoma following chemical orchiectomy: potential role of hypogonadism in myeloma proliferation.

We present a case of a 55 year old man with multiple myeloma who underwent autologous stem cell transplantation and subsequently developed testicular myeloma. Testicular enlargement was observed only after treatment of an incidental prostatic adenocarcinoma with chemical orchidectomy at a time when myeloma was controlled systemically. A subsequent bilateral surgical orchiectomy revealed plasmacytoma in both testis. Enhanced production of B-lymphocytes after castration has been reported and implicates testosterone as a possible negative regulator of B-cell production. We propose that the androgen deficient state may have contributed to the development of plasmacytoma of the testes in our patient. The regulatory role of sex steroids in B-cell development is discussed.

Adenocarcinoma↗
PubMed1997

Autologous and allogeneic transplantation for multiple myeloma at a single centre.

We report the results of a consecutive series of patients who underwent autologous (auto) (40), allogeneic (allo) (22) or syngeneic transplantation (2) for multiple myeloma (MM) at our centre. Median age at diagnosis was 45.5 (auto) and 43 (allo) years. Most patients had stage 2 (27% auto; 27% allo) or stage 3 (62% auto; 50% allo) disease and 73% demonstrated chemosensitivity prior to transplant. Median time from diagnosis to transplant was 18.6 months (auto) and 16.4 months (allo). Standard conditioning regimens were used. Median time to neutrophil engraftment was 11 days (7-18) (auto) and 18 days (13-24) (allo) and median time to platelet engraftment was 11 days (6-60) and 18 days (13-105), respectively. Ninety-day mortality was 5% (auto) and 27% (allo). Median follow-up was 15 months (6-48) (auto) and 42 months (24-52) (allo). Three-year progression-free survival (PFS) was 17 +/- 10% (auto) and 22 +/- 9% (allo) and 3-year overall survival (OS) was 74 +/- 11% (auto) and 32 +/- 10% (allo). Autologous transplantation for MM is a safe procedure with good OS although disease progression following transplant is frequent. Allogeneic transplantation has a high procedure-related mortality and PFS comparable to autologous transplantation but OS is poor. The early mortality and high OS of autologous transplantation in MM compares favourably with both the results of allogeneic transplantation and published results of standard therapy in this retrospective analysis.

Adult↗
PubMed1996

Peripheral blood progenitor cell collections in multiple myeloma: predictors and management of inadequate collections.

Thirty-seven patients with previously treated multiple myeloma (MM) underwent peripheral blood progenitor cell (PBPC) collection following high-dose cyclophosphamide and GM-CSF or sequential IL-3 and GM-CSF. Patients with an inadequate collection were considered for a second or third collection. 25 patients underwent subsequent autotransplant. The only variable predictive of CFU-GM yield was the extent of prior melphalan therapy. All repeat collections were unsuccessful and patients infused with an autograft obtained from multiple sets of collections had a high incidence of delayed engraftment. We conclude that melphalan should be avoided or PBPC collection performed early in the disease course in patients who are potential transplant candidates.

Adult↗
PubMed1996

Detection of donor cell derived acute myelogenous leukaemia in a patient transplanted for chronic myelogenous leukaemia using fluorescence in situ hybridization.

The recurrence of leukaemia following allogeneic bone marrow transplantation appears to develop rarely in donor cells. However, the standard method for assigning the origin of recurrence, metaphase analysis, can be unreliable. We have applied the technique of fluorescence in situ hybridization (FISH) directly on archival Wright stained bone marrow slides obtained from a patient who developed acute myelogenous leukaemia (AML) following allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukaemia (CML). Using a chromosome-specific DNA probe we linked a chromosomal aberration, previously detected by conventional metaphase analysis, directly to morphologically identifiable blast cells. In this way we were able to assess cell-lineage involvement of the secondary leukaemia and assign a donor origin.

Adult↗
PubMed1994

Secondary malignancies after bone marrow transplantation in adults.

PURPOSE: The records of 557 consecutive adult recipients of allogeneic-related and -unrelated and syngeneic bone marrow transplants (BMTs) were reviewed to determine the incidence of secondary cancers. PATIENTS AND METHODS: Four hundred fifty-six patients were transplanted for acute lymphocytic leukemia (ALL; n = 79), acute myelogenous leukemia (AML; n = 182), and chronic myelogenous leukemia (CML; n = 195); 42 patients were transplanted for aplastic anemia (AA) and 59 for a variety of other hematologic and nonhematologic disorders, malignant and nonmalignant. Conditioning regimens included high-dose chemotherapy with or without total-body irradiation (TBI). Statistical analyses determined the cumulative incidence of developing a secondary cancer and elucidated the associated risk factors. Complete records (1 to 24 years of follow-up) on all patients were available. RESULTS: Nine patients developed 10 secondary cancers for a cumulative actuarial risk of 12% (95% confidence interval [CI], 4.3 to 23.0) 11 years after transplant. The age-adjusted incidence of secondary cancer was 4.2 times higher than that of primary cancer in the general population. Eight of the 10 were epithelial in origin and three were cutaneous. TBI and acute graft-versus-host disease (GVHD) with a severity > or = grade II were associated with the development of any secondary cancer. On the other hand, chronic GVHD was a risk factor only for the development of secondary skin neoplasms. CONCLUSION: Adult recipients of BMT face a significant risk of developing a secondary malignancy. Their risk is similar to that of other patients with hematologic malignancies who are treated with chemoradiotherapy only. Epithelial tumors, rather than the more commonly reported Epstein-Barr virus (EBV)-associated lymphomas, were most common. The fact that we did not routinely use T-cell-depleted marrow grafts nor anti-T-cell immunoglobulin for the treatment of acute GVHD may explain this variance.

Adolescent↗
PubMed1994

Pneumatosis intestinalis with free air mimicking intestinal perforation in a bone marrow transplant patient.

A case of pneumatosis intestinalis with perforation is reported in a patient after bone marrow allograft for chronic myeloid leukemia. Risk factors included the transplant, prolonged immunosuppression and neutropenia, graft-versus-host disease, extended use of corticosteroids, infection and lower gastrointestinal endoscopic biopsy. The literature is reviewed and a management plan for patients presenting with this complication is discussed.

Adult↗