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Biomedical subjects

S J Forman

Publications and source records attributed to S J Forman.

At least 127 records · Page 7Linked to original sources
PubMed1993

A prospective randomized comparison of total body irradiation-etoposide versus busulfan-cyclophosphamide as preparatory regimens for bone marrow transplantation in patients with leukemia who were not in first remission: a Southwest Oncology Group study.

Two novel preparatory regimens for conditioning of patients with leukemia for allogeneic bone marrow transplantation (BMT) from histocompatible sibling donors have been tested in a phase III trial under the auspices of the Southwest Oncology Group (SWOG 8612). These two regimens consisted either of fractionated total body irradiation and etoposide (FTBI/VP-16) or high-dose busulfan with cyclophosphamide (BU/CY). Only patients who had failed prior conventional management at least once were study eligible, ie, no patients with acute leukemia in first remission (CR) or in first chronic phase (CP) of chronic myelogenous leukemia (CML) participated. Patients were stratified according to the following risk criteria: "good-risk" patients were those who were in second CR of their acute leukemia or in accelerated phase (AP) of CML; "poor-risk" patients had further advanced stages of leukemia. During a 52-month period, 131 patients were registered of whom 122 (93%) were study eligible. Sixty-one eligible patients were randomized to the FTBI/VP-16 arm and 61 to the BU/CY regimen. Of these 122 patients, 114 (93%) proceeded to BMT according to protocol. Posttransplant immunosuppression to prevent graft-versus-host disease (GVHD) consisted of cyclosporine and prednisone (CSA/PSE). Neither overall survival nor disease-free survival (DFS) differed significantly between the two treatment groups (P = .89 and .69, respectively). Estimated DFS for "good-risk" patients who had been prepared with the FTBI/VP-16 regimen was 55% +/- 11%, as compared with patients treated with BU/CY whose DFS figure was 34% +/- 10% (P = .30). For "poor-risk" candidates, the DFS rates at 24 months were 17% +/- 6% (for FTBI/VP-16) and 24% +/- 8% (for BU/CY), respectively (P = .81). These figures do not differ significantly, especially in view of the fact that the "good-risk" patients prepared with the FTBI/VP-16 regimen were younger than those treated with BU/CY. Both regimens were well tolerated with no regimen-related deaths encountered during the 6-week period after BMT. This study also confirmed the efficacy of the CSA/PSE combination in the prevention of GVHD with 23 of 113 (20%) of BMT recipients developing moderate to severe acute GVHD. The leading cause for treatment failure was leukemic relapse (45 of the 114 BMT recipients suffered a recurrence of their leukemia), whereas 38 patients died without evidence of relapse. Thirty-one patients are alive and in continued CR after marrow transplantation; four are alive in relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Acalculous cholecystitis in bone marrow transplant patients.

BACKGROUND: Acalculous cholecystitis (ACC) is an uncommon disorder of the biliary tract, accounting for approximately 6% of acute cholecystitis cases. In this study, cholecystitis was seen in 8 of 770 bone marrow transplant recipients, with ACC occurring in five (63%). METHODS: Records of 592 allogenic and 150 autologous BMT patients were reviewed for risk factors associated with ACC. RESULTS: Only the number of blood transfusions administered and the use of total parenteral nutrition were associated with ACC development. ACC occurred in 4 of 42 (9%) allogeneic recipients who required exchange transfusion for ABO incompatibility. ACC developed in one autogolous recipient alongside venoocclusive disease of the liver. There was no association between ACC development and preparative regimen, cyclosporine usage, graft versus host disease, or cytomegalovirus infection. CONCLUSIONS: ACC occurs more frequently in patients after ABO incompatible BMT requiring exchange transfusion than in other transplant recipients.

ABO Blood-Group System↗
PubMed1993

Busulfan/etoposide--initial experience with a new preparatory regimen for autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia.

Current intensive chemotherapy for acute nonlymphoblastic leukemia (ANLL) results in a complete remission in the majority of patients. Unfortunately, the duration of remission is short and most of the patients will experience a relapse of their underlying disease. Autologous bone marrow (BM) transplantation is being explored as a treatment modality designed to improve relapse-free survival. We have conducted a phase II trial exploring the combination of busulfan (16 mg/kg) and etoposide (60 mg/kg) in an attempt to improve antitumor efficacy using this novel preparative regimen. To date, 50 patients (48 with ANLL and 2 patients with biphenotypic acute leukemia) have been treated. The first 20 patients received unmanipulated BM; 28 patients subsequently received 4-hydroperoxycyclophosphamide (4-HC) (60 micrograms/mL)-purged bone marrow, and 2 patients with biphenotypic acute leukemia received both 4-HC (60 micrograms/mL) and etoposide (5 micrograms/mL)-purged BM. Thirty-four patients were in first complete remission (CR1), 12 patients in second complete remission (CR2), and 4 patients in relapse. The median time from first complete remission to BM harvest was 3 months (range, 0.8 to 4) compared with median time of 2 months (range, 1.5 to 5.0) for patients in second complete remission. The median time from harvest to transplant was 1 month for both groups (range, 0.4 to 36). A median of 0.7 x 10(8) (range, 0.2 to 1.4) mononuclear cells were infused. Patients achieved an absolute neutrophil count of > or = 500/microL at a median of 26 days (range, 13 to 96), an untransfused platelet count > or = 20,000/microL at a median of 56 days (range, 15 to 278) and a sustained hematocrit > or = 30% at a median of 50 days (range, 19 to 116). Twenty-six patients are alive and in continued CR. Follow-up of the surviving patients ranged from 6 months to 66 months with a median follow-up of 31 months. Patients receiving purged BM have an actuarial disease-free survival of 57% with a relapse rate of 28% compared with patients receiving unpurged BM whose actuarial disease-free survival is 32% with a relapse rate of 62% (P = .06 for relapse rate). The most significant extramedullary toxicities for this regimen are hepatic and cutaneous (including mucositis). The BU/VP-16 regimen is associated with a significant proportion of patients surviving disease free, especially in the group receiving purged BM. Whether this regimen offers a substantial improvement in disease-free survival over currently used regimens will require a prospective randomized study.

Adult↗
PubMed1993

Acute murine cytomegalovirus infection induces lethal hepatitis.

Events were examined that might contribute to mortality in acute murine cytomegalovirus (MCMV) infection after intraperitoneal inoculation. Specifically, viral replication in the liver, spleen, and pancreas and the concomitant biochemical abnormalities induced by MCMV during lethal and nonlethal acute viral infection were compared. Mortality was limited to susceptible strains of mice infected by the intraperitoneal (ip) route. In addition, the virus content of the lung, liver, spleen, and pancreas was 100- to 1000-fold greater with lethal infection in the ip-infected group than in those with nonlethal infection. Serum transaminase and lipase levels were markedly elevated in susceptible mice inoculated with MCMV ip. Histopathologic and immunocytochemical changes in the liver, coupled with elevated serum transaminase levels indicating severe hepatitis, appear sufficient to explain the early mortality seen with the ip route of infection.

Acute Disease↗
PubMed1993

Extended follow-up in 212 long-term allogeneic bone marrow transplant survivors. Issues of quality of life.

A group of 235 allogeneic marrow recipients were contacted at least one year following their BMT to obtain information on their quality of life; 212 (90%) agreed to participate in this survey. A total of 162 adults and 50 pediatric survivors were interviewed during clinic visits (5%) or over the telephone (95%). Changes in productive activity and marital status at the time of interview were studied, as well as the presence of physical symptoms and perception of a general sense of well-being. Older transplant recipients were observed to have a significantly higher incidence of chronic graft-versus-host disease, common colds, and skin changes when compared with pediatric transplant recipients (P < 0.01). Older subjects were also more likely to require any type of regular medication. Younger survivors were rated with a higher Karnofsky performance status and global subjective score. There were no significant differences between patients who received TBI as part of the conditioning regimen and those who did not, with the exception of increased cataract development in pediatric patients receiving TBI (P < 0.008). We conclude that most allogeneic marrow transplant survivors, especially those individuals of younger age at the time of their transplants, are doing well in the domains tested.

Adolescent↗
PubMed1992

Measurement of quality of life in bone marrow transplantation survivors.

This study was designed to assess the reliability and validity of a Quality of Life (QOL) instrument on a sample of 179 allogeneic Bone Marrow Transplant (BMT) survivors. The QOL-BMT tool was developed specifically for this population and was based on the investigators' prior research and a conceptual model of Quality of Life. Patients who were at least 100 days post BMT completed the 30 item visual analogue questionnaire. The instrument measured physical symptoms (e.g., weight loss, frequent colds, skin changes, cataracts, sexual problems), psychological symptoms (e.g., worry about recurrence, adjustment to illness), social concerns (e.g., relationship adjustment, return to work), and spiritual well-being (e.g., sense of control, future goals). Psychometric analysis of the instrument included measures of reliability and validity. The study findings demonstrate the unique aspects of QOL dimensions in BMT survivors and the value of QOL assessment in clinical practice and research.

Adaptation, Psychological↗
PubMed1992

Immunoarchitecture of normal human bone marrow: a study of frozen and fixed tissue sections.

To provide baseline information on the immunoarchitecture of normal bone marrow, we studied cryostat-cut, frozen, and paraffin-embedded, fixed tissue sections prepared from 21 core biopsies of normal bone marrow obtained during bone marrow harvests for transplantation. A large panel of antibodies was applied that included, for frozen tissue, Leu-6 (CD1), T11 (CD2), Leu-3a (CD4), Leu-1 (CD5), Leu-2a (CD8), J5 (CD10), My7 (CD13), Leu-11 (CD16), B4 (CD19), B1 (CD20), B2 (CD21), Tac (CD25), My9 (CD33), T200 (CD45), NKH-1 (CD56), kappa and lambda chains, beta F1, Ki-67, HLA-DR, TQ1, and keratin, and for fixed tissue, leukocyte common antigen (CD45), L26 (CD20), LN1 (CDw75), LN2 (CD74), LN3, LN4, LN5, MB1 (CD45R), MB2, MT1 (CD43), MT2 (CD45R), UCHL1 (CD45R0), BM1, Ki-1 (CD30), Leu-M1 (CD15), lysozyme, KP1 (CD68), actin, S100, neuron-specific enolase, vimentin, and keratin. On fresh-frozen sections CD19 and CD2 were the most reliable and sensitive markers for B and T cells, staining 5% and 9% of marrow cells, respectively. Immunoglobulins generally showed heavy background staining, which frequently precluded an accurate assessment. The CD4 to CD8 ratio in the bone marrow was reversed from that of peripheral blood. On fixed tissues, leukocyte common antigen was found in 14% of the marrow cells, corresponding roughly to the lymphocyte population. L26, a pan-B-cell marker, stained 3% of the marrow cells. Among the other B-cell markers, LN1 and MB2 stained a large number of cells (40% to 70%), indicating reactivity with cells of the myeloid or erythroid series in addition to lymphocytes. Among the T-cell markers, UCHL1 and MT1 stained 66% and 50% of the cells, respectively, which could be explained by their cross-reactivity with myeloid cells. Nonspecific myelomonocytic markers (Leu-M1, KP1, and lysozyme) also showed reactivity in a high percentage of cells. No particular architectural distribution patterns of B or T lymphocytes were noted in either frozen or fixed bone marrow specimens. The results of this study provide normal baseline data for the immunohistologic application of hematopoietic and lymphoid markers on frozen or fixed bone marrow biopsy specimens.

Adult↗
PubMed1992

The value of bronchoalveolar lavage and bronchial washings in the diagnosis of invasive pulmonary aspergillosis.

The objective of this study was to clarify conflicting reports of the sensitivity and specificity of bronchoalveolar lavage or bronchial washings for diagnosing invasive pulmonary aspergillosis. The study was a retrospective review of 300 consecutive patients in a tertiary referral centre subjected to 343 fiberoptic bronchoscopic procedures for the evaluation of pulmonary infiltrates. Classification of paired fungal culture and cytologic examination of bronchoalveolar lavage or bronchial washing fluid according to clinical, radiographic, histological and autopsy evidence of invasive pulmonary aspergillosis. One-hundred and fifteen deaths occurred, with a 58% autopsy rate. A diagnosis of invasive pulmonary aspergillosis was made in 21 immunosuppressed patients with 16 deaths. Bronchoalveolar lavage cytology showed aspergillus in 19 specimens (invasive pulmonary aspergillosis in 16), cultures yielded aspergillus in 41 (invasive pulmonary aspergillosis in ten), with both tests positive in nine. Cytology sensitivity was 64.0%, specificity 99.1%, positive predictive value 84.2%, and negative predictive value 97.2%. Culture sensitivity was 40.0%, specificity 90.3%, positive predictive value 24.4%, and negative predictive value 95.0%. Concordant cytology and culture sensitivity was 32.0%, specificity 99.7%, positive predictive value 88.9%, and negative predictive value 94.9%. In conclusion, when characteristic hyphae are visualized in bronchoalveolar lavage specimens from immunosuppressed patients with compatible clinical data, it is advisable to treat for presumptive invasive pulmonary aspergillosis.

Adult↗
PubMed1992

Pretransplant pulmonary function predicts cytomegalovirus-associated interstitial pneumonia following bone marrow transplantation.

STUDY OBJECTIVE: To determine the value of pulmonary function tests (PFTs) in predicting the development of human cytomegalovirus (CMV)-associated interstitial pneumonia (IP) in allogeneic bone marrow transplant (BMT) recipients. DESIGN: Nonrandomized, prospective, open-trial study. SETTING: Tertiary referral medical center. PATIENTS: 66 evaluable CMV-seropositive patients with hematologic malignancies who were undergoing allogeneic BMT. INTERVENTION: FEV1, FVC, FEV1/FVC, TLC, Dcoc/VA, PaO2, and P(A-a)O2 were measured on days -13, +33, and +44 following BMT. CMV-IP was diagnosed when typical roentgenographic findings developed with confirmatory positive bronchoalveolar lavage (BAL) using standard cytologic and/or rapid culture techniques. MEASUREMENT AND MAIN RESULTS: Univariate logistic regression analysis to predict the development of CMV-IP revealed significant associations with the day -13 and +33 percent predicted FEV1, FVC, and TLC (p < 0.01) but no associations with other PFT parameters or with changes in these parameters. Stepwise logistic regression analysis demonstrated that only BAL positivity for CMV (odds ratio 14.8; p = 0.0002) and day -13 percent predicted FEV1 (odds ratio 0.92; p = 0.0004) were significant independent predictors of CMV-IP. CONCLUSION: Pretransplant lung function is a previously unrecognized strong predictor and risk factor for the subsequent development of CMV-IP in BMT recipients.

Adolescent↗
PubMed1992

High-dose etoposide (VP-16)-containing preparatory regimens in allogeneic and autologous bone marrow transplantation for hematologic malignancies.

High-dose etoposide has been added to total body irradiation, cyclophosphamide, carmustine, or busulfan in preparatory regimens for allogeneic or autologous bone marrow transplantation for patients with leukemia, Hodgkin's disease, lymphoma, or multiple myeloma. The treatment results are encouraging, indicating that etoposide may be a valuable addition to the previously established regimens. Etoposide should be incorporated into collaborative, prospective trials to define its ultimate role in bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

The meaning of quality of life for bone marrow transplant survivors. Part 2. Improving quality of life for bone marrow transplant survivors.

Surviving bone marrow transplant (BMT) represents a major victory against malignant disease but also creates challenges of survivorship for patients and the professionals who care for them. Part 2 of this report presents the findings of a qualitative study (N = 119) related to improving quality of life (QOL) for BMT survivors. Results are shared based on BMT survivors' perceptions of (a) what makes QOL better, (b) what makes QOL worse, and (c) what doctors or nurses could do to enhance QOL. The findings of the study have been useful in constructing a quantitative instrument to measure QOL in BMT and in understanding the conceptual basis of QOL for the BMT population. Nursing interventions can improve the QOL for the BMT patient across all phases of the transplant process and long-term issues related to survival.

Bone Marrow Transplantation↗
PubMed1992

The meaning of quality of life for bone marrow transplant survivors. Part 1. The impact of bone marrow transplant on quality of life.

Quality of life (QOL) is an important concept in cancer nursing and has particular significance for bone marrow transplant (BMT). BMT survivors are faced with the demands of acute transplant symptoms as well as chronic illness demands posttransplant. The purpose of this study was to explore the concept of QOL for BMT survivors and to gain understanding of nursing interventions that may improve QOL in this population. The conceptual framework for this study was derived from the model of QOL developed by Ferrell, Grant, and Padilla (1989) that depicts the QOL domains of physical well-being, psychological well-being, social concerns, and spiritual well-being. This qualitative study consisted of a one-time interview of 119 BMT survivors using six open-ended questions. The items were based on previous research of the authors and content validity was established by a panel of BMT experts. Content analysis was performed on verbatim written responses to six questions regarding BMT and QOL. Part one of this two-part report provides analysis based on the questions regarding the meaning of QOL to BMT survivors and the impact of BMT on QOL.

Adult↗
PubMed1991

Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report.

We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

Adult↗
PubMed1991

Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia during first complete remission.

Fifty-three patients with high-risk acute lymphoblastic leukemia (ALL) under age 50 with a histocompatible sibling donor received high-dose radiochemotherapy followed by allogeneic bone marrow transplantation (BMT). The high-risk factors used to identify the patients were: white blood cell count at initial presentation, cytogenetic abnormalities, age, extramedullary leukemic infiltration, and time from initial therapy to complete remission. Patients with one or more of the above risk factors who received BMT have a disease-free survival of 61% with a median follow-up of 66 months (range 11 months to 10.6 years), and an actuarial relapse rate of 10%. This study demonstrates that patients with high-risk ALL achieve a significant disease-free survival and cure rate with the use of allogeneic fully matched sibling BMT. However, a properly designed prospective study comparing the outcome of BMT with the best currently available chemotherapy data is required to define the ultimate role of BMT in this group of patients.

Adolescent↗
PubMed1991

A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group.

BACKGROUND: Cytomegalovirus (CMV)-associated interstitial pneumonia is a major cause of death after allogeneic bone marrow transplantation. We conducted a controlled trial of ganciclovir in recipients of bone marrow transplants who had asymptomatic pulmonary CMV infection. We also sought to identify risk factors for the development of CMV interstitial pneumonia. METHODS: After bone marrow transplantation, 104 patients who had no evidence of respiratory disease underwent routine bronchoalveolar lavage on day 35. The 40 patients who had positive cultures for CMV were randomly assigned to either prophylactic ganciclovir or observation alone. Ganciclovir (5 mg per kilogram of body weight intravenously) was given twice daily for two weeks and then five times per week until day 120. RESULTS: Of the 20 culture-positive patients who received prophylactic ganciclovir, 5 (25 percent) died or had CMV pneumonia before day 120, as compared with 14 of the 20 culture-positive control patients (70 percent) who were not treated prophylactically (relative risk, 0.36; P = 0.01). No patient who received the full course of ganciclovir prophylaxis went on to have CMV interstitial pneumonia. Four patients treated with ganciclovir had maximal serum creatinine levels greater than or equal to 221 mumol per liter (2.5 mg per deciliter), as compared with none of the controls (P = 0.029). Of the 55 CMV-negative patients who could be evaluated, 12 (22 percent) had CMV pneumonia--a significantly lower rate than in the untreated CMV-positive control patients (relative risk, 0.33; P = 0.003). The strongest predictors of CMV pneumonia were a lavage-fluid culture that was positive for CMV and a CMV-positive blood culture, both from specimens obtained on day 35. CONCLUSION: In recipients of allogeneic bone marrow, asymptomatic CMV infection of the lung is a major risk factor for subsequent CMV interstitial pneumonia. Prophylactic ganciclovir is effective in preventing the development of CMV interstitial pneumonia in patients with asymptomatic infection.

Adolescent↗
PubMed1991

Amplification by the polymerase chain reaction of hypervariable regions of the human genome for evaluation of chimerism after bone marrow transplantation.

We combined the polymerase chain reaction (PCR) with oligonucleotide hybridization as a novel and sensitive technique to evaluate posttransplant chimerism. Specific oligonucleotides for hybridization were synthesized homologous to tandemly repetitive core sequences of regions with a variable number of tandem repeats (VNTRs). Polymorphisms at such loci result from allelic differences in the number of repeats. Primers flanking the repeat region of each of the corresponding VNTRs were used for amplification. Recipient and donor pretransplant DNA and recipient posttransplant DNA were amplified. The resultant fragments were analyzed after gel electrophoresis either by hybridization in-gel or after Southern transfer. To confirm our findings, we also performed standard assays of restriction fragment length polymorphisms (RFLPs). Evaluation of 13 selected cases indicated mixed chimerism (4), complete chimerism (5), recurrence of leukemia (2), and endogenous repopulation of hematopoiesis (2) after marrow transplantation. Sensitivity of the method was determined by mixing various proportions of recipient and donor DNA; the limit of detection of the minor component in a mixture was 0.1%. PCR data correlated with RFLP data in all cases except two in which PCR proved more sensitive than RFLP. PCR amplification of VNTRs combined with oligonucleotide hybridization is a novel technique for documenting posttransplant chimerism and has advantages over RFLP analysis: high sensitivity, use of small amounts of DNA (250 ng), ease of preparation of DNA, elimination of need for restriction enzymes, and the ability to complete studies in 2 days.

Base Sequence↗
PubMed1991

Persistence of bcr-able gene expression following bone marrow transplantation for chronic myelogenous leukemia in chronic phase.

The bcr-abl RNA transcript is the molecular counterpart of the Philadelphia chromosome and is detectable by an extremely sensitive polymerase chain reaction assay in most patients with chronic myelogenous leukemia. To determine the effectiveness of ablative radiochemotherapy and bone marrow transplantation in eradicating molecular evidence of the malignant clone, we assayed for bcr-abl RNA expression in specimens from 19 patients with CML in chronic phase (CP) who have survived for at least one year post-BMT. We correlated these results with the patients' remission status based on cytogenetic analysis and BM morphology, and with evidence of mixed hematopoietic chimerism by analysis of RBC antigen and DNA restriction fragment length polymorphism patterns. Thirteen of the 19 patients had detectable bcr-abl RNA at some time following BMT. Twelve of these patients have remained in remission by morphologic and karyotypic criteria from 16.6 to 63.7 months following BMT. One of these 13 patients relapsed both by cytogenetic and clinical criteria at 28.1 months after BMT. Six of these 13 patients are still positive at the time of their most recent analysis. Only two patients have evidence for mixed chimerism of normal hematopoietic elements by either RBC antigen or DNA RFLP patterns. These results suggest that, in some patients transplanted for CML in CP, small numbers of residual leukemic cells may persist or reappear transiently without leading to clinical relapse. The definition of complete remission in CML may need to be revised in light of the enhanced ability to detect minimal residual disease by PCR technology.

Adult↗