Search PubMed⌕ Search

Biomedical subjects

J R Wingard

Publications and source records attributed to J R Wingard.

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

Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis.

The records of 239 immunosuppressed patients receiving amphotericin B for suspected or proven aspergillosis were reviewed to determine rates of nephrotoxicity, dialysis, and fatality. The mean and median durations of treatment were 20.4 and 15.0 days, respectively. The creatinine level doubled in 53% of patients and exceeded 2.5 mg/dL in 29%; 14.5% underwent dialysis; and 60% died. A multivariate Cox proportional hazards analysis showed that patients whose creatinine level exceeded 2.5 mg/dL (hazard ratio [HR], 42.02; P<.001), allogeneic bone marrow transplantation (BMT) patients (HR, 6.34; P<. 001), and autologous BMT patients (HR, 5.06; P=.024) were at greatest risk for requiring hemodialysis. Use of hemodialysis (HR, 3. 089; P<.001), duration of amphotericin B use (HR, 1.03 per day; P=. 015), and use of nephrotoxic agents (HR, 1.96; P=.017) were associated with greater risk of death, whereas patients undergoing solid organ transplantation were at lowest risk (HR, 0.46; P=.002). These data indicate that elevated creatinine levels during amphotericin B treatment are associated with a substantial risk for hemodialysis and a higher mortality rate, but the risks vary in different patient groups.

Adolescent↗
PubMed1999

Can 40 seconds of compassion reduce patient anxiety?

PURPOSE: To use a standardized videotape stimulus to assess the effect of physician compassion on viewers' anxiety, information recall, treatment decisions, and assessment of physician characteristics. PARTICIPANTS AND METHODS: One hundred twenty-three healthy female breast cancer survivors and 87 women without cancer were recruited for this study. A randomized pretest/posttest control group design with a standardized videotape intervention was used. Participants completed the State-Trait Anxiety Inventory (STAI), an information recall test, a compassion rating, and physician attribute rating scales. RESULTS: Women who saw an "enhanced compassion" videotape rated the physician as warmer and more caring, sensitive, and compassionate than did women who watched the "standard" videotape. Women who saw the enhanced compassion videotape were significantly less anxious after watching it than the women in the other group. Nevertheless, information recall was relatively low for both groups, and enhanced compassion did not influence patient decisions. Those who saw the enhanced compassion videotape rated the doctor significantly higher on other positive attributes, such as wanting what was best for the patient and encouraging the patient's questions and involvement in decisions. CONCLUSION: The enhanced compassion segment was short, simple, and effective in decreasing viewers' anxiety. Further research is needed to translate these findings to the clinical setting, where reducing patient anxiety is a therapeutic goal.

Adult↗
PubMed1999

Thalidomide in children undergoing bone marrow transplantation: series at a single institution and review of the literature.

Thalidomide has one of the most notorious drug histories because of its teratogenicity. Its widespread use in the 1960s led to a worldwide epidemic of phocomelia in inborns; this in turn led to its complete ban in most of the world. However, it has now been licensed for selected indications including graft-versus-host-disease (GVHD) after bone marrow transplantation, wasting associated with tuberculosis and human immunodeficiency virus infection, and leprosy. Little is known, however, about its use in children in these settings. Therefore, we report our experience and review the literature on thalidomide in children for GVHD after bone marrow transplantation. We studied 6 patients, 2 with chronic GVHD, 2 with acute GVHD, and 2 with acute GVHD progressing into chronic disease. One patient with chronic GVHD had a complete response, whereas the other had a partial response. Side effects consisted primarily of sedation and constipation, which are reported previously and well known side effects. None had neuropathy. One patient had rash, eosinophilia, and early pancreatitis that began shortly after initiation of thalidomide, persisted, and resolved only after discontinuation of thalidomide. Eosinophilia and pancreatitis are both previously unreported side effects or associated findings of thalidomide treatment. Review of the literature reveals three major studies of thalidomide in GVHD; of these two included children and adults together, and one in which age range of patients was not mentioned. In addition, four series of children receiving only thalidomide are reported. These series contained 1 to 14 patients each. Results show efficacy in at least 50% of children with chronic GVHD and little or no efficacy in children with exclusively acute GVHD. Side effects are similar to those reported in adults and consisted mostly of sedation and constipation, both of which subsided over time and resolved after discontinuing the drug. We speculate on the reasons for which thalidomide is more effective in chronic, compared with acute, GVHD in children, and make recommendations for future study.

Acute Disease↗
PubMed1998

Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation.

We report the results of a phase III open-label, randomized, multicenter trial comparing tacrolimus/methotrexate to cyclosporine/methotrexate for graft-versus-host disease (GVHD) prophylaxis after HLA-identical sibling marrow transplantation in patients with hematologic malignancy. The primary objective of this study was to compare the incidence of moderate to severe (grade II-IV) acute GVHD. Secondary objectives were to compare the relapse rate, disease-free survival, overall survival, and the incidence of chronic GVHD. Patients were stratified according to age (<40 v >/=40) and for male recipients of a marrow graft from an alloimmunized female. There was a significantly greater proportion of patients with advanced disease randomized to tacrolimus arm (P = . 02). The incidence of grade II-IV acute GVHD was significantly lower in patients who received tacrolimus than patients in the cyclosporine group (31.9% and 44.4%, respectively; P = .01). The incidence of grade III-IV acute GVHD was similar, 17.1% in cyclosporine group and 13.3% in the tacrolimus group. There was no difference in the incidence of chronic GVHD between the tacrolimus and the cyclosporine group (55.9% and 49.4%, respectively; P = .8). However, there was a significantly higher proportion of patients in the cyclosporine group who had clinical extensive chronic GVHD (P = . 03). The relapse rates of the two groups were similar. The patients in the cyclosporine arm had a significantly better 2-year disease-free survival and overall survival than patients in the tacrolimus arm, 50.4% versus 40.5% (P = .01) and 57.2% versus 46.9% (P = .02), respectively. The significant difference in the overall and disease-free survival was largely the result of the patients with advanced disease, 24.8% with tacrolimus versus 41.7% with cyclosporine (P = .006) and 20.4% with tacrolimus versus 28% with cyclosporine (P = .007), respectively. There was a higher frequency of deaths from regimen-related toxicity in patients with advanced disease who received tacrolimus. There was no difference in the disease-free and overall survival in patients with nonadvanced disease. These results show the superiority of tacrolimus/methotrexate over cyclosporine/methotrexate in the prevention of grade II-IV acute GVHD with no difference in disease-free or overall survival in patients with nonadvanced disease. The survival disadvantage in advanced disease patients receiving tacrolimus warrants further investigation.

Adolescent↗
PubMed1998

Measurement of absolute concentration and viability of CD34+ cells in cord blood and cord blood products using fluorescent beads and cyanine nucleic acid dyes.

Conventional flow cytometric methods for CD34+ cell counting may be affected by the high number of nucleated red blood cells or nonviable cells in cord blood and its products. We developed a simple flow cytometric no-wash procedure that avoids these shortcomings because it provides absolute CD34+ cell counts and assesses cell viability. Samples were incubated with phycoerythrin (PE)-labeled anti-CD34 (Becton Dickinson Immunocytometry Systems [BD], San Jose, CA) and peridinin chlorophyll protein (PerCP)-labeled anti-CD45 (BD) in bead-containing TRUCOUNT tubes (BD). After red cell lysis with a fixative-free reagent, the impermeant nucleic acid dye YO-PRO-1 (Molecular Probes, Eugene, OR) was added and samples were analyzed on a single-laser FACSCalibur (BD). A comparison with the ProCOUNT progenitor cell assay (BD) in 57 samples revealed excellent correlation of results (r = 0.98, intercept -0.2 cells/microl, slope 1.01). Precision studies conveyed coefficients of variation of 6.4 and 8.9% at concentrations of 35 and 16 CD34+ cells/microl, respectively. In untreated and leukocyte-enriched cord blood 4.5+/-3.8% of CD34+ cells were stained by YO-PRO-1, representing apoptotic or necrotic cells. In post-thawing cryopreserved samples this number increased to 10.4+/-5.5%. Isotype controls showed very low blank values of viable cells (0.1+/-0.4 cells/microl, maximum 2.4) and seemed unnecessary. We found no washing-related alteration of results in 35 samples, indicating that the method may also be performed with cell washing. Replacing YO-PRO-1 with TO-PRO-3 facilitated four-color analysis of subpopulations of viable CD34+ cells on a FACSCalibur equipped with a second (diode) laser. We found the proposed method to be a rapid, efficient, and flexible procedure that improved validity of CD34+ cell counts.

Antigens, CD34↗
PubMed1998

An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation.

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT = 24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV = 8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n = 34, INT; n = 32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P = 0.49). Greater than 90% of all patients were graded as failures (> or = 5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1-2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.

Adult↗
PubMed1998

Successful salvage using mismatched umbilical cord blood transplant in an adult with recurrent acute myelogenous leukemia failing autologous peripheral blood progenitor cell transplant: a case history and review.

We report a 26-year-old female with AML, FAB classification M5 who was initially treated with induction therapy consisting of idarubicin and cytarabine followed by high-dose cytarabine and autologous peripheral blood progenitor cell (PBPC) transplant for consolidation. The patient remained in remission for 1 month post-PBPC transplant, when relapse was noted. Reinduction therapy with idarubicin, cytarabine and etoposide was unsuccessful, and the patient underwent an unrelated, two-antigen mismatched umbilical cord blood (UCB) transplant for salvage after melphalan plus total body irradiation. Complications post transplant included veno-occlusive disease, delayed engraftment, and acute grade III graft-versus-host disease (GVHD). The patient remains in remission 1 year post transplant. This study demonstrates the salvage capability of UCB transplantation for refractory leukemia and its potential use in adult patients.

Adult↗
PubMed1998

Relationship of tacrolimus (FK506) whole blood concentrations and efficacy and safety after HLA-identical sibling bone marrow transplantation.

A randomized clinical trial comparing tacrolimus with cyclosporine, both with short-course methotrexate, as prophylaxis against graft-vs.-host disease (GVHD) in allogeneic HLA-matched sibling bone marrow transplant patients was conducted. Cyclosporine was dosed to achieve a target concentration range between 150 and 450 ng/mL during the first 8 weeks after transplant. For tacrolimus, the target concentration range was 10-30 ng/mL during the first 8 weeks after transplant. A gradual tapering schedule of 20% per month during months 3-6 was then conducted for patients in both treatment arms. The efficacy of the immunosuppressive regimen was determined by the rate of acute GVHD grades II-IV The toxicity of the immunosuppressive regimen was determined by the occurrence of the creatinine exceeding 2 mg/dL, the creatinine doubling the baseline value, or the necessity for hemodialysis. Correlations between blood concentrations and efficacy and toxicity parameters were assessed. For both tacrolimus and cyclosporine, increasing blood concentrations were associated with greater renal dysfunction. For cyclosporine, there was a nonsignificant trend to an increased incidence of grades II-IV acute GVHD with lower cyclosporine blood concentrations (<300 ng/mL). In contrast, there did not appear to be a relationship between the blood concentrations of tacrolimus and the occurrence of acute GVHD. This suggests that optimization of efficacy while minimizing the risk for nephrotoxicity could be achieved by dosing tacrolimus to a targeted range between 10 and 20 ng/mL.

Adolescent↗
PubMed1998

Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia.

We conducted a prospective, randomized, double-blind study comparing amphotericin B colloidal dispersion (ABCD) with amphotericin B in the empirical treatment of fever and neutropenia. Patients with neutropenia and unresolved fever after > or = 3 days of empirical antibiotic therapy were stratified by age and concomitant use of cyclosporine or tacrolimus. Patients were then randomized to receive therapy with ABCD (4 mg/[kg.d]) or amphotericin B (0.8 mg/[kg.d]) for < or = 14 days. A total of 213 patients were enrolled, of whom 196 were evaluable for efficacy. Fifty percent of ABCD-treated patients and 43.2% of amphotericin B-treated patients had a therapeutic response (P = .31). Renal dysfunction was less likely to develop and occurred later in ABCD recipients than in amphotericin B recipients (P < .001 for both parameters). Infusion-related hypoxia and chills were more common in ABCD recipients than in amphotericin B recipients (P = .013 and P = .018, respectively). ABCD appeared comparable in efficacy with amphotericin B, and renal dysfunction associated with ABCD was significantly less than that associated with amphotericin B. However, infusion-related events were more common with ABCD treatment than with amphotericin B treatment.

Adolescent↗
PubMed1998

The effect of overnight storage of leukapheresis stem cell products on cell viability, recovery, and cost.

The cost of harvesting, processing, and freezing multiple peripheral blood stem cell (PBSC) products could easily exceed that of bone marrow harvest. To reduce costs while maintaining product viability, we examined the effect of overnight storage on PBSC products. Sixteen consecutive leukapheresis samples from 12 patients were examined prospectively. Each initial leukapheresis product was stored overnight on ice (median temperature 15 degrees C) after adding an equal amount of M199 culture medium containing heparin. After overnight storage, the product was combined with the next day PBSC harvest if required and processed/frozen per protocols. Parameters measured before and after storage include cell count and differential, viability, bacterial cultures, and colony-forming unit (CFU) assays. The results show that the median cell concentration during storage was 7.12 x 10(7)/ml and the median length of storage was 20 h. After storage, the median viability and nucleated cell recovery were 100% and 99.5%, respectively. In addition, 98% recovery of CFU-GM was achieved. No clotting or bacterial contamination was detected. All 12 patients studied engrafted promptly. In addition, 124 similarly treated patients were retrospectively analyzed. Of these, 48% required > or = 2 large-volume leukaphereses to achieve the target cell dose. As a result of overnight storage, 150 final products, instead of 224, were processed and cryopreserved. This difference is equivalent to 33% cost savings. Again, all patients were transplanted and engrafted successfully. In conclusion, overnight storage and pooling of two consecutive PBSC products are safe, reduce cost, and allow for optimum laboratory staffing.

Adolescent↗
PubMed1998

Quality of life following bone marrow transplantation.

Quality of life (QOL) studies in bone marrow transplantation (BMT) recipients are increasingly regarded as one of the ways to evaluate the outcome of BMT. Recent reports continue to detail acute and late psychosocial problems in BMT recipients. More and more longitudinal studies of QOL and comparisons of QOL outcomes after BMT or alternative nontransplant treatments are appearing in the literature. Several interventions that may promote positive effects on psychosocial adjustment are suggested: attention to patients' coping styles by the healthcare team, encouragement of aerobic exercise, attempts to lessen patients' levels of anxiety, and the presence of at least one staff member identified by the patient as an important source of support over time--all may have positive influences on QOL.

Bone Marrow Transplantation↗
PubMed1998

Acute oral pain and mucositis in bone marrow transplant and leukemia patients: data from a pilot study.

The purposes of this prospective, repeated-measures descriptive pilot study were to describe patterns of acute oral pain and mucositis in patients receiving a bone marrow transplant or high-dose chemotherapy for leukemia, and to test procedures and instruments before initiating a larger intervention study. A nonprobability, purposive selection process was used to enroll 18 patients admitted to two acute care inpatient hospital units for bone marrow transplantation or leukemia therapy at a university health sciences center in the southeastern United States. Data were collected at baseline, then daily through patient interviews, oral examination, and chart review for at least 3 weeks or until discharge. Research variables were pain intensity, intolerable pain, verbal descriptors of pain, pain relief, and use of pain relief strategies (Pain Assessment Form), mucositis (erythema and ulceration) in eight anatomic locations of the oral cavity (Oral Mucositis Index), voice/talking (Oral Assessment Guide), and mood states (11-item Brief Profile of Mood States). Mild to moderate pain occurred in nearly 70% of patients and was described as "tender," "irritating," and "sore." Patients used pain medicines, mouth care, and mental and physical activities to relieve pain, and reported partial overall relief of pain. Mucositis was mild, with the tongue and buccal and labial mucosa most commonly affected with erythema and the buccal mucosa with ulceration. Voice/talking were only mildly impaired, and mood disturbance was mild. Patterns of pain, mucositis, and mood disturbance were consistent with each other and followed the trajectory described in previous research. Results suggest that nurses should continue to assess these symptoms vigorously and assist patients in selecting multiple management strategies. Research using repeated-measures designs in this acutely ill inpatient population is challenging and needs careful attention by researchers. The results have been used to improve the ongoing larger intervention study.

Acute Disease↗
PubMed1998

Efficacy of low-dose dopamine in preventing amphotericin B nephrotoxicity in bone marrow transplant patients and leukemia patients.

This study evaluated the efficacy of low-dose dopamine for prevention of amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Seventy-one patients undergoing cytoreductive therapy who required amphotericin B were randomly assigned in an unblinded fashion to a group receiving continuous-infusion low-dose dopamine (3 microgram/kg/min) or a group receiving no dopamine. Amphotericin B was dosed at 0.5 or 1.0 mg/kg/day based on computerized tomography scan results or presence of positive blood cultures. No patient received saline boluses. The rate of nephrotoxicity, severity as graded by Southwest Oncology Group toxicity criteria, and time to each grade of nephrotoxicity were compared between the two groups. Eighty percent of the no-dopamine group and 66.7% of the dopamine group developed nephrotoxicity, defined as a 1.5-fold or greater increase in baseline serum creatinine level (P = 0.20). No statistical difference was noted at any grade of nephrotoxicity between the two groups. Thirty-four percent of patients in the no-dopamine group versus 17.6% in the dopamine group had a 2.5-fold or greater increase in serum creatinine level, which was not statistically significant (P = 0.0888). Ten patients developed grade IV nephrotoxicity and were withdrawn from the study, 7 in the no-dopamine group and 3 in the dopamine group (P = 0.19). The time to each grade of nephrotoxicity was also not significantly different for the two groups. Eleven adverse drug reactions were reported in the dopamine group in comparison to one in the no-dopamine group. Thus, dopamine offers little in the way of prevention of nephrotoxicity associated with amphotericin B therapy. Although the significance of drug reactions in the dopamine group is not clearly established due to lack of cardiac monitoring in the no-dopamine group, dopamine therapy is not without complications.

Adolescent↗
PubMed1997

Successful engraftment after primary graft failure in aplastic anemia using G-CSF mobilized peripheral stem cell transfusions.

A 19-year-old male underwent allogeneic BMT for severe aplastic anaemia (SAA) from his HLA- and blood group-identical sister. He was conditioned with cyclophosphamide (CY) and single fraction total lymphoid irradiation (TLI). GVHD prophylaxis consisted of FK506 and a short course of methotrexate. The patient failed to achieve durable trilineage hematopoietic engraftment. There was no significant myeloid response to GM-CSF or G-CSF. Evaluation of FACS-sorted peripheral T cells from the patient by fluorescence in situ hybridization (FISH) revealed mixed chimerism (44% host origin). Fifty-three days after the first BMT, he was treated with G-CSF primed, unmanipulated PBSC transfusions (5.28 x 10(8)/kg mononuclear, 4.28 x 10(6)/kg CD34+, 292.51 x 10(6)/kg CD3+ cells) from his original donor without reconditioning. FK506 was continued at the same dose. Neutrophil recovery to 0.5 x 10(9)/l and platelet engraftment to 20 x 10(9)/l was achieved 11 and 27 days following the first dose of allogeneic PBSC transfusion, respectively. On day 23 a repeat FISH on the patient's sorted peripheral T lymphocytes revealed 91% donor origin T cells. The patient is currently well with a stable engraftment 6 months following allogeneic PBSC transfusion, with no signs of acute of chronic GVHD.

Adult↗
PubMed1997

Efficacy of amphotericin B lipid complex injection (ABLC) in bone marrow transplant recipients with life-threatening systemic mycoses.

Bone marrow transplant (BMT) recipients are at increased risk of invasive fungal disease as a result of the profound neutropenia associated with transplantation. Amphotericin B lipid complex injection (ABLC, ABELCET) was developed to preserve the broad spectrum and fungicidal activity of conventional amphotericin B while avoiding its associated nephrotoxicity. ABLC was made available to physicians in an emergency-use program to treat seriously ill patients with advanced fungal infections who had failed to respond to previous systemic antifungal therapy (mostly amphotericin B), had experienced nephrotoxicity or severe acute toxicity due to amphotericin B or other drugs, or had pre-existing renal disease. Of 59 clinically evaluable BMT recipients with presumed or confirmed fungal infections, 31 (53%) responded to treatment: 23 (39%) were cured and eight (14%) improved. For 38 mycologically evaluable patients, pathogens were eradicated in 19 (50%). For 30 patients who began ABLC treatment with a serum creatinine > 221 mumol/l, significant reductions were observed at weeks 1 to 3 (P < 0.01) and 6 (P < 0.001). Trends in serum creatinine during ABLC therapy between autologous and allogeneic transplant recipients were similar. In summary, the results of this evaluation indicate that ABLC appears to be less nephrotoxic than conventional amphotericin B as well as an effective treatment for BMT recipients with presumed or confirmed fungal infections.

Adolescent↗
PubMed1997

Lack of interaction between tacrolimus (FK506) and methotrexate in bone marrow transplant recipients.

Tacrolimus (FK506) is a macrolide lactone effective in the control of graft-versus-host disease (GVHD). An interaction between high-dose methotrexate and a macrolide antibiotic (pristinamycin) leading to prolonged methotrexate exposure has been described. Because a randomized prospective trial comparing tacrolimus with cyclosporine (both in combination with methotrexate) following allogeneic BMT showed the tacrolimus plus methotrexate regimen to be more effective in prevention of GVHD, we assessed methotrexate pharmacokinetics in a subgroup of the participants of this trial to evaluate the possibility that an interaction of FK506 and methotrexate was the explanation for the clinical findings. Mean and median methotrexate levels at various time-points after the day 1 and 6 methotrexate doses were comparable in the tacrolimus and cyclosporine cohorts and were elevated in only three of 70 study patients. Area under the curve (AUC) concentrations were also similar after the day 1 and 6 methotrexate doses. Thus, no significant interaction between tacrolimus and methotrexate is apparent and the differences in efficacy between tacrolimus and cyclosporine are unlikely to be attributable to pharmacologic interactions with methotrexate.

Adolescent↗
PubMed1997

Allogeneic bone marrow transplantation with matched unrelated donors for patients with hematologic malignancies using a preparative regimen of high-dose cyclophosphamide and fractionated total body irradiation.

Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor is effective therapy for patients with bone marrow failure states and those with hematologic malignancies. However, only a minority of them will have an HLA-identical sibling donor; unrelated donors, matched or partially mismatched, have been used successfully for patients lacking a related donor. Even though results with allogeneic transplants using unrelated donors are encouraging, the incidence of complications including graft-versus-host disease (GVHD) and graft rejection or late graft failure is increased compared to identical sibling transplants. The combination of cyclophosphamide and total body irradiation (TBI) has been used as an effective preparative regimen for allogeneic transplants, however, the total dosage and dosing schedule of both the cyclophosphamide and TBI has varied significantly among studies. To decrease the rate of graft rejection and late graft failure with volunteer donors, we evaluated a preparative regimen of high-dose cyclophosphamide (200 mg/kg over 4 consecutive days, days -8, -7, -6, -5) followed by fractionated TBI (1400 cGy administered in eight fractions over 4 days, days -4, -3, -2, -1). GVHD prophylaxis included FK506 and methotrexate. From July 1993 to January 1996, 43 adult patients, median age 38 years (range 18-58 years), were treated with this preparative regimen. Seventeen patients had low-risk disease and 26 had high-risk disease. Thirty-one donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Seven additional pairs were minor mismatched at the HLA-A or HLA-B loci. Four other donor/recipient pairs were HLA-A,-B, and -DR identical by serology but allele mismatched at either DRB1 or DQB. Forty patients were evaluable for myeloid engraftment. Engraftment occurred in all 40 patients at a median of 19 days. There were no cases of graft rejection or late graft failure. Nephrotoxicity was the primary adverse event with 26 patients (60%) experiencing a doubling of their creatinine. Hepatic veno-occlusive disease occurred in seven patients, six of whom had high-risk disease. All patients who had relapsed or refractory disease prior to BMT achieved a complete remission following BMT. Six patients transplanted for high-risk disease relapsed a median of 377 days post-BMT. None of the patients with low-risk disease have relapsed following transplant; the Kaplan-Meier survival for those patients with low-risk disease is 62% and 37% for those patients transplanted with high-risk disease (P = 0.0129). The median Karnofsky performance status is 100% (range 70-100%). Therefore, a preparative regimen of high-dose cyclophosphamide and fractionated TBI is an acceptable regimen for patients receiving an allograft from unrelated donors.

Adolescent↗