Search PubMed⌕ Search

Biomedical subjects

G Heller

Publications and source records attributed to G Heller.

At least 109 records · Page 6Linked to original sources
PubMed1994

Stage 4 neuroblastoma diagnosed at more than 1 year of age: gross total resection and clinical outcome.

The importance of gross total resection of the primary tumor in stage 4 neuroblastoma is controversial. The purpose of this study was to assess the impact of gross total resection of the primary tumor on clinical outcome in patients with stage 4 neuroblastoma diagnosed at more than 1 year of age. The authors retrospectively analyzed 70 newly diagnosed cases treated with one of five regimens of increasing dose-intensity. Outcome variables included survival time from diagnosis, and time to local recurrence or local tumor progression. Patient variables analyzed for impact on survival included age, anatomic location of the primary tumor, radiation treatment of the primary site, complete resection at diagnosis, gross total resection (GTR) at any time in the course of therapy, and treatment protocol dose-intensity. GTR was accomplished in seven patients at the time of diagnosis and in 32 patients after chemotherapy. The likelihood of complete gross resection after chemotherapy increased with greater protocol intensity. The only patient variables that correlated with improved survival were GTR (P = .03) and chemotherapy protocol (P = .01). GTR was also associated with improved local control. Although an independent effect of GTR on survival was not demonstrable because complete resection after chemotherapy correlated strongly with increasing protocol intensity, its association with improved overall survival was striking. These results support a continued role for GTR in high-risk neuroblastoma, along with intensive chemotherapy.

Adolescent↗
PubMed1994

A prospective randomized double-blind trial of bolus urokinase in the treatment of established Hickman catheter sepsis in children.

BACKGROUND: The incidence of Hickman catheter sepsis is 10% to 40%, with resultant catheter loss in one third of infections. Urokinase causes dissolution of colonized intracatheter fibrin thrombi and may improve salvage. STUDY AIMS: To evaluate the efficacy of 12-hour-interval slow-push urokinase infusion in addition to standard antibiotic therapy in the treatment of catheter sepsis in a pediatric oncology population. METHODS: A two-arm randomized double-blind trial was undertaken, with catheter salvage rate as the end point. Patients with Hickman catheter sepsis were randomized after culture data confirmed the diagnosis. The study drug was administered by a slow intravenous push and given at 12-hour intervals for a total of four doses. The catheters were aspirated after 1 hour. RESULTS AND CONCLUSIONS: The trial was stopped after 41 patients were entered into the study; 18 patients received a placebo, and 23 received the urokinase. In the placebo group, six catheters were lost; in the urokinase group, eight were lost. The rate of bacterial clearance was equivalent for both. After administration of the study drug, each group had three episodes of fever and chills; two of these resulted in hypotension (one in each group). The authors conclude that slow-push urokinase infusion during established Hickman catheter sepsis does not result in improved catheter salvage or bacterial clearance. Slow intravenous push infusions in this setting may provoke hemodynamic instability even after initiation of antibiotics.

Bacteria↗
PubMed1994

Highly effective induction therapy for stage 4 neuroblastoma in children over 1 year of age.

PURPOSE: To test the efficacy of a protocol for poor-risk neuroblastoma that builds on the following: (1) our favorable previously reported results with dose-intensive use of cyclophosphamide; (2) our retrospective analysis of neuroblastoma chemotherapy reports, which supported the value of high-dose cisplatin and etoposide (VP-16); and (3) the Goldie-Coldman hypothesis that rapid cytoreduction plus the use of non-cross-resistant chemotherapy combinations will decrease the risk of drug resistance. PATIENTS AND METHODS: The N6 protocol included seven courses of high-dose chemotherapy plus surgical resection of bulk disease. Courses 1, 2, 4, and 6 consisted of 6-hour intravenous infusions of cyclophosphamide 70 mg/kg/d on days 1 and 2 (ie, 140 mg/kg per course), a 72-hour intravenous infusion of doxorubicin 75 mg/m2 and vincristine 0.1 mg/kg beginning day 1, and vincristine 1.5 mg/m2 intravenous bolus on day 9. Courses 3, 5, and 7 consisted of 2-hour intravenous infusions of VP-16 200 mg/m2/d on days 1 to 3 (ie, 600 mg/m2 per course), and 1-hour intravenous infusions of cisplatin 50 mg/m2/d on days 1 to 4 (ie, 200 mg/m2 per course). Courses were to start after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Response was defined by international criteria. RESULTS: Among 24 consecutive previously untreated patients diagnosed with stage 4 neuroblastoma at more than 1 year of age, 21 patients achieved a complete or very good partial remission; one patient had no evidence of disease except by iodine-131-metaiodobenzylguanidine (MIBG) scan, which was markedly improved; and one patient had resolution of extensive metastatic disease, but still had an incompletely resected primary tumor. The sole patient to have a poor response had clinical features at diagnosis that are atypical for neuroblastoma, namely, 8 years of age and an unknown primary tumor. Severe toxicities included myelosuppression, mucositis, and hearing deficits. CONCLUSION: The N6 approach reliably achieves significant cytoreduction against stage 4 neuroblastoma. This may eventuate in an improved cure rate, since consolidative treatments using myeloablative therapy, immunotherapy, or biologic response modifiers such as cis-retinoic acid are most likely to be effective against minimal residual disease.

Abdominal Neoplasms↗
PubMed1994

Treatment of acute promyelocytic leukemia with all-trans retinoic acid: an update of the New York experience.

In an ongoing study, we treated 79 patients with a molecular diagnosis of acute promyelocytic leukemia (APL) using all-trans retinoic acid (RA) for remission induction. Newly diagnosed patients received cytotoxic chemotherapy for consolidation, and previously treated patients received extended all-trans RA therapy, or a radionuclide-conjugated monoclonal antibody as post-remission treatment. Unlike studies in Europe, full-dose chemotherapy was not given during induction for patients who developed leukocytosis. Overall, 43 of 49 newly diagnosed patients (88%) and 25 of 30 previously treated patients (83%) achieved complete remission. We did not encounter de novo resistance to all-trans RA in any patient who was positive for PML/RAR-alpha rearrangements by reverse transcription polymerase chain reaction analysis. Ten patients died during induction from intracranial or pulmonary hemorrhage (six patients) or the 'retinoic acid syndrome' (four patients). The use of leukapheresis or low-dose chemotherapy (hydroxyurea or cytosine arabinoside) for drug-induced leukocytosis did not decrease early mortality. Compared to historical controls, early mortality was not affected by treatment with all-trans RA; however, both relapse-free and overall survival were significantly increased. Maintenance therapy with all-trans RA was associated with short remission duration, and relapses while taking the drug were universally associated with resistance to further retinoid treatment. We conclude that the use of all-trans RA for remission induction, with or without full-dose chemotherapy, has significantly increased the survival of patients with APL. While early mortality has not yet been reduced, the avoidance of full-dose chemotherapy during induction has significantly reduced early morbidity. The major outstanding clinical issue is the development of strategies that maximize safety in high-risk patients for whom intracranial hemorrhage remains the major cause of death.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Treatment of acute promyelocytic leukemia with all-trans retinoic acid: an update of the New York experience.

In an ongoing study, we treated 79 patients with a molecular diagnosis of acute promyelocytic leukemia (APL) using all-trans retinoic acid (RA) for remission induction. Newly diagnosed patients received cytotoxic chemotherapy for consolidation, and previously treated patients received extended all-trans RA therapy, or a radionuclide-conjugated monoclonal antibody as post-remission treatment. Unlike studies in Europe, full-dose chemotherapy was not given during induction for patients who developed leukocytosis. Overall, 43 of 49 newly diagnosed patients (88%) and 25 of 30 previously treated patients (83%) achieved complete remission. We did not encounter de novo resistance to all-trans RA in any patient who was positive for PML/RAR-alpha rearrangements by reverse transcription polymerase chain reaction analysis. Ten patients died during induction from intracranial or pulmonary hemorrhage (six patients) or the 'retinoic acid syndrome' (four patients). The use of leukapheresis or low-dose chemotherapy (hydroxyurea or cytosine arabinoside) for drug-induced leukocytosis did not decrease early mortality. Compared to historical controls, early mortality was not affected by treatment with all-trans RA; however, both relapse-free and overall survival were significantly increased. Maintenance therapy with all-trans RA was associated with short remission duration, and relapses while taking the drug were universally associated with resistance to further retinoid treatment. We conclude that the use of all-trans RA for remission induction, with or without full-dose chemotherapy, has significantly increased the survival of patients with APL. While early mortality has not yet been reduced, the avoidance of full-dose chemotherapy during induction has significantly reduced early morbidity. The major outstanding clinical issue is the development of strategies that maximize safety in high-risk patients for whom intracranial hemorrhage remains the major cause of death.

Antigens, Surface↗
PubMed1994

Morbidity and costs of remission induction therapy with all-trans retinoic acid compared with standard chemotherapy in acute promyelocytic leukemia.

With the recent pressure to control health care expenditures, the costs of patient participation in clinical trials, especially in their earliest phases, have come under increasingly intense scrutiny. We therefore reviewed our experience in patients with acute promyelocytic leukemia (APL) who were treated during the first US trial of a new experimental drug, all-trans retinoic acid (RA). The purpose of the review was to evaluate parameters of patient morbidity and financial cost associated with the use of all-trans RA compared with standard chemotherapy for induction of complete remission in newly-diagnosed patients with APL. We retrospectively compared outcomes of consecutive patients treated during the first 2 years of our studies that used all-trans RA for remission induction (1990-1992) with an identical number of patients consecutively treated with standard chemotherapy (cytosine arabinoside plus an anthracycline) during the immediately preceding period (1985-1990). Responding patients in both groups received post-remission chemotherapy. Evaluation parameters included transfusions of packed red blood cells and platelets, use of anti-bacterial and anti-fungal drugs, duration of fever, time to remission, length of hospital stay, hospital charges, and both overall and relapse-free survival. Thirty patients were evaluated in each group. Complete remission was achieved in 26 patients (87%) treated with all-trans RA, and 24 patients (77%) treated with chemotherapy (p = 0.5). In the chemotherapy group, there were five early deaths (four from hemorrhage, one from sepsis); one other patient was resistant to treatment and died at 6 months. Four patients in the all-trans RA group died prior to response from complications of the 'retinoic acid syndrome'. The median time to complete response by all criteria was 41 days (range, 18-78) for the all-trans RA group and 50 days (range, 24-121) for patients who received conventional chemotherapy (p = 0.2). Looking only at patients who achieved remission, chemotherapy-treated patients required a significantly greater number of platelet transfusions (medians, 14 vs. 4; p < 0.001) and packed red blood cell transfusions (15 vs. 4; p < 0.001). Patients who received chemotherapy also experienced a significantly larger number of days with fever (13 vs. 6; p = 0.01) that was reflected in a greater median number of days on combination antibiotics (35 vs. 21; p = 0.001) and Amphotericin B (20 vs. 0; p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Development of a new intensive therapy for acute lymphoblastic leukemia in children at increased risk of early relapse. The Memorial Sloan-Kettering-New York-II protocol.

BACKGROUND: Improved survival of children with acute lymphoblastic leukemia (ALL) has made it more difficult to develop new protocols to further improve results. The authors report the pilot experience with the Memorial Sloan-Kettering-New York-II (MSK-NY-II) protocol, based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity. METHODS: Forty-four of 46 consecutive patients were randomized to one of four regimens varying only in the sequence and mode of administration of the drugs during the first 48 hours of therapy, while the kinetics of the disappearance of the leukemic cells from the bone marrow was monitored with bone marrow aspirates and biopsies on days 0, 2, 7, and 14. RESULTS: Thirty-two high-risk and 12 average-risk patients were randomized. The marrow contained less than 25% blasts in 74.4% and 92.9% by day 7 and 14, respectively. Ninety-three percent achieved remission. Regimens beginning with daunorubicin achieved a greater and more rapid reduction in leukemic cells than those starting with cyclophosphamide. Daunorubicin infusion produced a more rapid cytoreduction than daunorubicin bolus. Two of 41 patients who achieved remission relapsed, and there was one death in remission. With a median follow-up of 54+ months, the event-free survival (EFS) rate was 86% +/- 10%. Disease-free survival (DFS) rate at 48 months was 93%. The estimated 4-year EFS rate for the high-risk and average-risk patients were 83 +/- 14% and 93 +/- 10%, respectively. Four of 18 patients given daunorubicin bolus and 0 of 18 patients given daunorubicin infusion who were monitored with serial echocardiograms had significant decrease in cardiac function (P = 0.10). The major toxicity of the therapy was infections, with 35% of patients developing serious infections during induction and consolidation. Half the patients had an episode of bacteremia from the venous catheter during the 2 years of maintenance. CONCLUSIONS: Close monitoring of kinetics of cytoreduction can rapidly distinguish between similar therapies, and the surrogate end-point may reduce the need for the long follow-up periods that may still be required to demonstrate differences in EFS. Continuous infusion of daunorubicin had less cardiotoxicity with faster antileukemic activity than bolus infusion. The MSK-NY-II protocol with a 86% 4-year EFS rate and a 95% DFS rate was a promising new regimen for the treatment of average-risk and high-risk ALL.

Adolescent↗
PubMed1993

Treatment of Diamond-Blackfan anemia with recombinant human interleukin-3.

This report describes the response of eighteen Diamond-Blackfan anemia (DBA) patients to recombinant human interleukin-3 (rhIL-3). rhIL-3 was administered subcutaneously once daily on an escalating dose schedule (0.5 to 10 micrograms/kg/d). The rhIL-3 dose was escalated every 21 days until erythroid response was attained, grade III or IV nonhematologic toxicity was observed, or the maximum rhIL-3 dose was reached. Four patients experienced clinically significant erythroid responses. Two of the responders were steroid-dependent and transfusion-independent, while two were steroid-independent and transfusion-dependent. Baseline clinical or laboratory parameters, in particular in vitro bone marrow erythroid progenitor assays, were not useful in predicting rhIL-3 response. rhIL-3 administered at 5 to 10 micrograms/kg/d was associated with an increase in total white blood cell count, secondary to increases in neutrophils, eosinophils, and lymphocytes. Patients experienced a dose-dependent elevation in absolute eosinophils across the entire dose range. Two of the responding patients remain on maintenance rhIL-3, without diminution of effect at 244 and 370 + days. rhIL-3 was discontinued in the other two responders, because of the development of deep venous thrombi.

Adolescent↗
PubMed1993

Primary peripheral nodal lymphoma in children.

BACKGROUND: In this series of 208 pediatric patients with non-Hodgkin (NHL) studied from 1971 to 1986, 84 patients (40.4%) had nodal lymphomas; 40 (19.2%) of these patients had peripheral nodal lymphoma and 44 (21.2%) had mediastinal lymphoma. METHODS: Forty pediatric patients with primary peripheral nodal lymphoma were treated at Memorial Sloan-Kettering Cancer Center with the LSA2-L2 protocol from July 1971 to January 1986. Informed consent was obtained from all patients and/or guardians. RESULTS: There were 26 male patients and 14 female patients, with a median age of 10 years. Two patients had Stage I disease, 5 Stage II, 9 Stage III, 8 Stage IVA (< 25% blasts in the bone marrow), and 16 Stage IVB (> 25% blasts in the bone marrow). The last patient with Stage IVB disease was entered in 1977, a time when the philosophy of treatment for leukemia-lymphomas had not yet evolved completely. Most of these lymphomas were high-grade lymphoblastic lymphomas, followed by immunoblastic lymphomas and reticulosarcomas. The event-free survival rate of this group of patients was 75%, with all patients having completed therapy, and a median observation time of more than 10 years without therapy. The lymphoma-free survival rate was 80%. Sex, age, and stage were not of prognostic significance. There was no significant difference in survival between patients with lymphoblastic and histiocytic lymphomas (75% versus 64%, respectively). There was no significant difference in survival between the patients with high-grade and medium-grade lymphomas (75% versus 78%, respectively). Lactic dehydrogenase (LDH) in this primary site was not indicative of extent or bulk of disease and did not affect survival negatively. Radiation therapy and dose intensity of chemotherapy influenced survival by promoting rapid and more complete cell kill, helping prevent the emergence of resistant cells. CONCLUSIONS: Although primary peripheral nodal lymphoma usually is disseminated at diagnosis, it is still a highly curable disease when treated aggressively. The lymphoma-free survival rate for patients with primary nodal NHL with marrow involvement is 75%, and this subsequently has led to a different philosophy in the treatment of high-risk leukemias and lymphoma-leukemias with the NY-I and NY-II protocols, with excellent results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Beneficial impact of peripheral blood progenitor cells in patients with metastatic breast cancer treated with high-dose chemotherapy plus granulocyte-macrophage colony-stimulating factor. A randomized trial.

BACKGROUND: This study compared the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with peripheral blood-derived hematopoietic progenitor cells (PBP) as support for patients receiving high-dose chemotherapy and assessed the adequacy of these strategies as alternatives to autologous bone marrow rescue. METHODS: The authors studied patients with metastatic breast carcinoma who had a major response to conventional chemotherapy or had achieved a complete remission by surgical resection of all known metastases. They were treated with carboplatin 1500 mg/m2, etoposide 1200 mg/m2, and cyclophosphamide 5.0 g/m2. Before this high-dose chemotherapy, the patients had been randomly assigned to one of two hematopoietic support strategies: GM-CSF alone (Group 1) or GM-CSF-primed PBP and GM-CSF (Group 2). Autologous bone marrow was harvested from all patients for use only in the event of persistent pancytopenia with marrow aplasia on day 15. RESULTS: A total of 18 patients were treated. Randomization was halted after the initial 10 patients because of the significant advantages for patients in Group 2 in comparison with those in Group 1 in regard to (1) the median number of days to absolute neutrophil count 0.5 x 10(9)/l (12 versus 21) and platelet count to 50 x 10(9)/l (13 versus 23), (2) platelet transfusions (3 versus 15.5), and (3) episodes of neutropenic sepsis (0 versus 4, respectively). One patient in Group 1 died from treatment-related complications. All patients in Group 1 required bone marrow reinfusion. No patient in Group 2 required bone marrow reinfusion, and no early mortality was observed in this group. Eight subsequent patients were treated with PBP and GM-CSF (Group 3). This group was more heavily pretreated than Groups 1 or 2 and had a slower hematologic recovery than Group 2. However, none of these patients required bone marrow reinfusion. The four patients in Group 1 that did not have early bone marrow rescue all had neutrophil counts of 0.0 on day 15. For Groups 2 and 3, the neutrophil counts on day 15 ranged from 0.3-2.1 x 10(9)/l (median, 1.9) and from 0.2-2.1 x 10(9)/l (median 0.6), respectively. CONCLUSIONS: The use of PBP plus GM-CSF accelerated hematologic recovery after this chemotherapeutic regimen compared with GM-CSF alone; there were reduced morbidity and platelet transfusion requirements. Recovery was sufficiently rapid that PBP were an acceptable alternative to autologous bone marrow transplantation in patients receiving high-dose carboplatin, etoposide, and cyclophosphamide.

Adult↗
PubMed1993

Successful treatment of Diamond-Blackfan anemia with interleukin 3.

This report describes the response of 18 Diamond-Blackfan anemia (DBA) patients to recombinant human interleukin 3 (rhIL-3). rhIL-3 was administered s.c. once daily on an escalating dose schedule (0.5-10 micrograms/kg/day). The rhIL-3 dose was escalated every 21 days until erythroid response was attained, grade III or IV nonhematologic toxicity was observed, or the maximal rhIL-3 dose was reached. Four patients experienced clinically significant erythroid responses. Two of the responders were steroid-dependent and transfusion-independent, while two were steroid-independent and transfusion-dependent. Baseline clinical or laboratory parameters, in particular in vitro bone marrow erythroid progenitor assays, were not useful in predicting rhIL-3 response. Two of the responding patients remain on maintenance rhIL-3 without diminution of effect at 490 and 855+ days. rhIL-3 was discontinued in the other two responders because of the development of deep venous thrombi.

Animals↗
PubMed1993

Treatment of spinal epidural neuroblastoma xenografts in rats using anti-GD2 monoclonal antibody 3F8.

Epidural neuroblastoma xenografts in nude rats causing paraparesis were treated with intravenous injection of an anti-GD2 monoclonal antibody 3F8. Metastatic or primary epidural tumors in humans cause rapid neurologic compromise. Treatment is often unsatisfactory. An animal model was established to study antibody targeted therapy of epidural tumor. Human neuroblastoma was xenotransplanted into the thoracic epidural space of nude rats. When paraparesis developed, animals were treated intravenously with an anti-GD2 monoclonal antibody, 3F8, either alone or radiolabeled with 131Iodine. Improvement in neurologic function occurred in 2 of 20 (10%) animals receiving no treatment or control antibody, 14 of 17 (82%) animals receiving 3F8 alone and all 9 animals receiving 131I-3F8 (p < 0.0001 for 3F8 or 131I-3F8 vs. control). Six animals treated with 3F8 alone recovered normal neurologic function and remained well until sacrifice 10 days later. Four animals treated with 3F8 alone had no tumor evident on pathologic examination. The percent injected dose of 131I-3F8/g tumor in 5 samples ranged from 0.73% to 3.8%. These observations demonstrate that neoplastic epidural compression of the spinal cord in the rat can be treated successfully with intravenous unmodified monoclonal antibody and that signs of neurologic dysfunction can be reversed. The potential of this approach in treating patients with epidural tumors and other neoplasms, especially those that are not sensitive to chemotherapy or radiotherapy, deserves to be explored.

Animals↗
PubMed1993

Osteogenic sarcoma with clinically detectable metastasis at initial presentation.

PURPOSE: Chemotherapy and surgery have improved the length of survival for patients with osteogenic sarcoma (OS) who present without metastatic disease. We reviewed our experience with patients with OS who presented with clinically detectable metastasis to determine the prognostic factors and the effects of surgery on the primary tumor and on metastatic disease. PATIENTS AND METHODS: From 1975 to 1984 we treated 62 patients who had previously untreated OS with metastasis detected at presentation. All of these patients received intensive chemotherapy that included high-dose methotrexate; doxorubicin; and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. The intent of surgery was resection of the primary tumor and metastatic disease. RESULTS: Survival was extremely poor; only 11% of patients survived, with a median survival of 20 months. Survival was not affected by use of preoperative chemotherapy versus immediate surgery, and did not correlate with serum lactate dehydrogenase (LDH) level, alkaline phosphatase level, or the site of the primary tumor. Survival did correlate with age, location of metastatic disease, histologic response to preoperative chemotherapy, and completeness of surgical resection of all sites of tumor. Resection of all sites of tumor identified at initial presentation was necessary for survival. CONCLUSION: OS that presents with metastatic disease has a very poor prognosis with therapy, although therapy has achieved good results for patients without metastasis detected at diagnosis. Aggressive surgical resection of tumor is necessary for survival. The use of novel therapies at initial presentation is justified with this group of patients.

Adolescent↗
PubMed1992

Myeloid and lymphoid chimerism after T-cell-depleted bone marrow transplantation: evaluation of conditioning regimens using the polymerase chain reaction to amplify human minisatellite regions of genomic DNA.

Determining both myeloid and lymphoid chimerism after T-cell-depleted allogeneic bone marrow transplantation (BMT) could be helpful in the understanding of the biology of engraftment and could provide a rational method of assessing the ability of different conditioning regimens to promote engraftment. We prospectively investigated the role of different pretransplant conditioning regimens in 29 leukemic patients post-BMT by assessing myeloid and T-cell chimerism using a rapid and sensitive polymerase chain reaction (PCR) method. Minisatellites are hypervariable regions of DNA consisting of tandem repeats of a core nucleotide sequence, and allelic polymorphism results from differences in the number of the repeats. We used this variation to distinguish between donor and recipient cells post-BMT. Seventeen patients (9 sibling and 8 unrelated donors) received conditioning with hyperfractionated total body irradiation (TBI), thiotepa, and cyclophosphamide (Cy). Of the other 12 patients (all sibling donors), 11 received TBI plus Cy plus another agent: VP16, carboplatinum, or AZQ. One patient received TBI plus thiotepa plus VP16. All but one of the patients studied received marrow from HLA-identical donors. PCR analysis confirmed donor lymphoid engraftment within 8 days of transplant in six of six patients studied. All granulocyte DNA was of donor origin within the first 4 weeks of transplant, regardless of the conditioning regimen. The day +28 T cells were exclusively of donor origin in 14 of 17 patients who received TBI plus thiotepa plus Cy, but were mixed chimeric in 10 of 12 patients who received other conditioning regimens (P < .001). Early graft rejection was seen in one unrelated transplant recipient conditioned with TBI plus thiotepa plus Cy. Late graft failure was observed in 3 of 12 patients with mixed T-cell chimerism and in none of 16 patients with full donor chimerism at day +28. However, 5 of 16 patients who had complete T-cell chimerism at day +28 developed acute graft-versus-host disease (GVHD), whereas no patient with mixed chimerism had acute GVHD. Our results indicate that minisatellite PCR is a rapid and sensitive method for assessing chimerism post-BMT, that the donor T cells are important for consistent durable engraftment, and that TBI plus thiotepa plus Cy may be superior to the other regimens studied in inducing full donor chimerism. Larger numbers and longer follow-up are necessary to confirm these data and also to assess the relationship between complete donor T-cell chimerism and leukemia-free survival.

Adolescent↗
PubMed1992

T-cell-depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission.

We prospectively evaluated the efficacy of T-cell-depleted bone marrow transplantation (BMT) in adults with de novo acute nonlymphocytic leukemia (ANLL) in first complete remission (CR), with regard to relapse-free survival and incidence of graft-versus-host disease (GvHD). Thirty-one patients older than 16 years (range, 16.5 to 43.2) received T-cell-depleted grafts for this purpose from related HLA/MLC-compatible donors. Twelve of the patients were older than 30 years at the time of transplantation. Patients were prepared with hyperfractionated total body irradiation (HFTBI; 1,375 to 1,500 cGy) and high-dose cyclophosphamide (120 mg/kg). T cells were removed from the marrow grafts by a two-step soybean lectin agglutination and sheep red blood cell (sRBC)-rosette procedure, achieving a 2.5- to 3-log depletion of clonable T lymphocytes. No additional prophylaxis against GvHD was administered. The median age at transplantation was 28.8 years; the median interval from diagnosis to transplantation was 3.8 months, and from CR was 2.7 months. Seventy-four percent received consolidation after remission induction therapy. The product-limit estimate of disease-free survival (DFS) at 3 years is 45% (95% confidence interval [CI], 24% to 66%), and the cause-specific probability of relapse is 13%. The median follow-up of the survivors is 72 months (range, 34.5 to 95.6). Median time to achieve a sustained absolute neutrophil count of 500 or greater was 16 days, and to maintain an untransfused platelet count of 20,000 or greater was 20 days. Five patients suffered immune-mediated graft rejection. Three patients developed grade I to II acute GvHD limited to the skin, which resolved promptly with brief courses of systemic steroids. None of the patients has developed clinically apparent chronic GvHD or a secondary lymphoproliferative disorder, and no patient is receiving immunosuppressive therapy. T-cell-depleted BMT by the method reported here is a favorable option as postremission therapy for adults with de novo ANLL in first remission who have an HLA/MLC-compatible related donor, and it is not associated with an increased risk of relapse posttransplant.

Adolescent↗