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Biomedical subjects

D L Porter

Publications and source records attributed to D L Porter.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stem cell transplantation for metastatic breast cancer: analysis of tumor contamination.

The purpose of this study was to determine the efficacy, engraftment kinetics, effect of bone marrow tumor contamination, and safety of high-dose therapy and granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood progenitor cell (PBPC) support for patients with responding metastatic breast cancer. Forty two patients underwent G-CSF (10 microg/kg) stimulated PBPC harvest. PBPC and bone marrow aspirates were analyzed by histologic and immunocytochemical methods for tumor contamination. Thirty-seven patients received high-dose therapy consisting of cyclophosphamide 6 g/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) given as an infusion over 4 d followed by PBPC reinfusion and G-CSF (5 microg/kg) support. No transplant related deaths or grade 4 toxicity was recorded. CD34+ cells/kg infused was predictive of neutrophil and platelet recovery. With a median follow-up of 38 months, three year survival was 44% with relapse-free survival of 19%. Histological bone marrow involvement, found in 10 patients, was a negative prognostic factor and was associated with a median relapse-free survival of 3.5 months. Tumor contamination of PBPC by immunohistochemical staining was present in 22.5% of patients and found not to be correlated with decreased survival. G-CSF stimulated PBPC collection followed by a single course of high dose chemotherapy and stem cell infusion with G-CSF stimulated marrow recovery leads to rapid, reliable engraftment with low toxicity and promising outcome in women with responding metastatic breast cancer.

Adult↗
PubMed1999

Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: impact on the delivery of local-regional radiation therapy.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. PATIENTS AND METHODS: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. RESULTS: Overall and disease-free survival rates at 18 months were 83% (+/- 4%) and 77% (+/- 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%-80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%-24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. CONCLUSION: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.

Adult↗
PubMed1999

Long-term follow-up of patients who achieved complete remission after donor leukocyte infusions.

Donor leukocyte infusions (DLI) can induce a direct graft-vs-leukemia (GVL) reaction and restore complete remission for patients who relapse after allogeneic bone marrow transplantation (BMT). A critical and unanswered concern is the long-term safety and durability of DLI. To determine remission duration, long-term toxicity, and survival after DLI-induced remissions, we identified 73 patients who achieved complete remission after DLI. Follow-up information was obtained for 66 of the 73 patients, including 39 patients with chronic myelogenous leukemia (CML) and 27 patients with other diseases. Median follow-up for all patients was 32 months; the probability of survival at 1, 2, and 3 years was 83% (95% confidence interval [CI] 74-92), 71% (60-83), and 61% (49-74), respectively. For CML, survival probability at 1, 2, and 3 years was 87% (76-98), 76% (62-90), and 73% (58-88). For other diseases, survival probability at 1 and 2 years is 77% (61-93) and 65% (46-84). Five of 39 patients with CML relapsed, and 11 of 27 patients with other diseases relapsed. Treatment-related toxicity accounted for 10 deaths. Extended follow-up shows that DLI-induced remissions are durable, especially for patients with CML. Late relapses still occur, however, and toxicity remains significant. Continued follow-up will best define the long-term GVL effects of DLI, especially for diseases other than CML.

Adolescent↗
PubMed1999

The graft-versus-leukemia effects of allogeneic cell therapy.

Until recently, the only cure for relapse after allogeneic bone marrow transplantation (BMT) has been a second BMT. Recently, infusions of leukocytes collected from the original transplant donor have been used to induce a direct graft-versus-leukemia (GVL) reaction in patients with relapsed disease. Adoptive immunotherapy with donor leukocyte infusions (DLI) results in complete remission for 60-80% of patients with relapsed chronic-phase CML; therapy is also effective for relapse of diseases other than CML, although response rates are lower. Adoptive immunotherapy induces remissions for the majority of patients with post-transplantation Epstein-Barr virus-related lymphomas and other viral-associated illnesses. The extraordinary success of DLI demonstrates that it is now possible to harness the GVL potential of the human immune system for clinical benefit. The necessary effector cells and target antigens required for GVL reactivity are poorly defined but are the subject of intensive investigation. Future trials will investigate strategies that retain and enhance the GVL effects while limiting toxicity from this therapy, and they may define methods of successful allogeneic adoptive immunotherapy outside the setting of allogeneic BMT.

Antigens, Neoplasm↗
PubMed1999

Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies.

PURPOSE: Histocompatible allogeneic donor leukocyte infusions (DLIs) were administered as primary cancer therapy in a phase I trial to determine (1) whether mixed chimerism could be detected without a prior allogeneic transplantation, (2) the toxicity of primary DLI, and (3) whether a graft-versus-tumor (GVT) reaction could be observed. PATIENTS AND METHODS: Eighteen patients were studied. Patients received interferon alfa-2b for a minimum of 4 weeks, followed by DLI (level 1). Patients with no toxicity or engraftment were eligible to receive cytarabine or cyclophosphamide followed by another course of DLI (level 2). Engraftment was determined using polymerase chain reaction amplification of donor and host-specific DNA polymorphisms. RESULTS: Donor cells were detected in the blood in 14 of 16 assessable patients within 1 hour of DLI. Chimerism detectable 4 weeks after DLI was observed in four patients, and five patients were not assessable. Prior autologous transplantation was associated with late chimerism (P =.0014). Acute graft-versus-host disease (GVHD) occurred in four of 16 assessable patients (grade 1, two patients; grade 2, one patient; grade 4, one patient). One patient with grade 4 acute GVHD developed pancytopenia. Only the four patients treated after prior autologous transplantation developed acute GVHD (P =.0005). Three of four patients with acute GVHD and late chimerism responded to primary DLI, and one patient was not assessable for response. CONCLUSION: Allogeneic adoptive immunotherapy resulted in sustained chimerism, acute GVHD, and a GVT response in heavily pretreated patients. This indicates that it may be possible to generate a direct GVT response for patients with malignancies without the need for intensive conditioning therapy immediately before DLI. Immunosuppression may be required for sustained donor cell engraftment.

Adolescent↗
PubMed1998

Chronic myelogenous leukemia: extending the prospects for cure.

Advances in our understanding of the molecular defects underlying this leukemia have led to novel therapeutic approaches that have not only altered the natural history of the disease but also apparently effected cures in some patients. The next step may be to offer the possibility of a cure to all patients. Allogeneic bone marrow and T cell transplantation shows promise in this regard.

Bone Marrow Transplantation↗
PubMed1998

Infusion of donor peripheral blood mononuclear cells to treat relapse after transplantation for chronic myelogenous leukemia.

Until recently, the only curative therapy for patients with chronic myelogenous leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) has been second allogeneic BMT. Recently, donor mononuclear cells have been given to patients with relapsed CML to induce a potent graft-versus-leukemia reaction and re-establish complete remissions in the majority of patients without the need for a second transplant. The extraordinary success of donor mononuclear cell infusions shows that it is possible to manipulate and harness the graft-versus-leukemia (GVL) reaction for clinical benefit. The identity of the effector cells and target antigens is unclear, but intensive investigation is beginning to define the complex cytokine and cellular interactions that mediate GVL reactivity. Current clinical trials are investigating strategies that will retain and enhance the GVL effects while limiting toxicity from this therapy. Ultimately, the ability to harness the GVL potential of allogeneic donor cells without excessive toxicity from graft-versus-host disease will be a central challenge in BMT and cellular immunotherapy.

Bone Marrow Transplantation↗
PubMed1997

Cycles of dose-intensive chemotherapy with peripheral stem cell support in persistent or recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: The objective was to determine the toxicity and surgically documented response rate of sequential high-dose chemotherapy with peripheral stem cell support in patients with persistent or recurrent cisplatin-sensitive ovarian cancer. METHODS: Fourteen patients (average age, 45 years) were treated with cyclophosphamide (4.5 g/m2), followed by granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral stem cell harvests. The subsequent regimen prescribed three courses of carboplatin (1 g/m2) and cyclophosphamide (1.5 g/m2 with 2-mercaptoethanesulfonate) every 2 weeks with stem cell support. This was followed by three courses of paclitaxel at 250 mg/m2 every 2 weeks with G-CSF support only. Six patients were entered on the basis of a positive second-look laparotomy and 8 patients had a first recurrence after at least a 6-month disease-free interval. RESULTS: Fourteen patients were entered and 12 patients completed all planned courses of therapy (mean time, 13 weeks). Normal hematopoiesis was reestablished after each cycle. Hospitalization for neutropenic fever occurred in 11/93 cycles (11.8%). Thirteen patients required blood transfusions and in 12 patients platelet transfusions were given. One patient had grade 3 neurotoxicity. An initial elevated CA 125 returned to normal in 7/8 patients (88%) and 71% of patients with measurable disease responded to therapy. There were 2 pathologic complete responders (PCR), making the PCR rate 2/14 or 14% (0-35%). CONCLUSION: Although this regimen was well tolerated and clinical response rates were high, the surgically documented response rate was not clearly superior to conventional salvage regimens in platinum-sensitive patients.

Adult↗
PubMed1997

Graft-versus-leukemia effect of allogeneic bone marrow transplantation and donor mononuclear cell infusions.

The significance and potency of GVL can no longer be argued. It is very clear that an allogeneic bone marrow graft provides an important GVL component critical to the success of BMT for many patients. The extraordinary success of donor MNC infusions to treat relapse after BMT shows that it is now possible to manipulate the GVL reaction to treat leukemia. The identity of the effector cells and target antigens remains unclear, but no doubt future experiments will begin to dissect out the complex cellular and cytokine interactions that mediate GVL reactivity. It also remains unclear whether GVL is distinct from GVHD; ultimately, the ability to harness GVL without excessive toxicity from GVHD will be a central challenge in BMT and cellular immunotherapy. There is now an excellent opportunity to understand the detailed mechanisms of GVL and to begin to design clinical strategies to harness the potent GVL effects of allogeneic donor cells for greater therapeutic benefit.

Animals↗
PubMed1997

Thrombocytopenia.

Determining the true cause of thrombocytopenia is a difficult and challenging clinical problem. Thrombocytopenia results from various causes, but ultimately occurs when platelets are destroyed, sequestered in the body, or not produced. The differential diagnosis of thrombocytopenia is extensive and complex, and there is a significant overlap among disorders. The advanced practice nurse must take a holistic approach to the patient, eliciting a detailed history and performing a comprehensive physical examination with special emphasis on the skin, abdominal, lymph node and neurologic consideration.

Adult↗
PubMed1997

Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.

PURPOSE: Recipients of allogeneic bone marrow transplants (BMTs) who have relapsed may attain complete remissions when treated with transfusions of leukocytes obtained from the original bone marrow donor. We performed a retrospective study to characterize better this new treatment modality. PATIENTS AND METHODS: We surveyed 25 North American BMT programs regarding their use of donor leukocyte infusions (DLI). Detailed forms were used to gather data regarding the original BMT, relapse, DLI, response to DLI, complications of DLI, and long-term follow-up evaluation. Reports of 140 patients were thus available for analysis. RESULTS: Complete responses were observed in 60% (95% confidence interval [CI], 51.9% to 68.1%) of chronic myelogenous leukemia (CML) patients who received DLI and did not receive pre-DLI chemotherapy; response rates were higher in patients with cytogenetic and chronic-phase relapse (75.7%; 95% CI, 68.2% to 83.2%) than in patients with accelerated-phase (33.3%; 95% CI, 19.7% to 46.9%) or blastic-phase (16.7%; 95% CI, 1.9% to 31.9%) relapse. The actuarial probability of remaining in complete remission at 2 years was 89.6%. Complete remission rates in acute myelogenous leukemia (AML) (n = 39) and acute lymphocytic leukemia (ALL) (n = 11) patients who had not received pre-DLI chemotherapy were 15.4% (95% CI, 9.6% to 21.2%) and 18.2% (95% CI, 6.6% to 29.8%), respectively. Complete remissions were also observed in two of four assessable myeloma patients and two of five assessable myelodysplasia patients. Complications of DLI included acute graft-versus-host disease (GVHD) (60%; 95% CI, 51.4% to 68.6%), chronic GVHD (60.7%; 95% CI, 50.3% to 71.1%), and pancytopenia (18.6%; 95% CI, 12.2% to 25.0%). Pre-DLI characteristics predictive of complete response in CML patients were post-BMT chronic GVHD, pre-DLI disease status of chronic phase, and time interval between BMT to DLI less than 2 years. Acute and chronic GVHD post-DLI were highly correlated with disease response (P < .00001). CONCLUSION: DLI results in complete remissions in a high percentage of patients with relapsed chronic-phase CML. Complete remissions are observed less frequently in patients with advanced CML and acute leukemia. GVHD and pancytopenia occur commonly; GVHD is highly correlated with response.

Actuarial Analysis↗
PubMed1996

Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation.

Relapse remains a significant problem after allogeneic bone marrow transplantation (BMT). For patients with relapsed chronic myelogenous leukemia (CML), infusions of donor mononuclear cells (MNC) provide a potent graft-versus-leukemia (GVL) reaction inducing complete remissions in the majority of patients. Little is known about the efficacy of donor MNC infusions for patients who relapse with other diseases. We have studied the GVL effects of donor MNC in eight patients with relapsed acute leukemia or myelodysplasia (MDS). One patient with relapsed MDS achieved complete remission and another patient had a transient response. Five of six non-responders died of progressive leukemia and one non-responder died of complications during second BMT. Three patients developed grade I-II acute GVHD responsive to immunosuppression. These data, and review of the literature, suggest that GVL induction with donor MNC infusions is less effective for patients with relapsed acute leukemia than for patients with relapsed CML; too few patients with relapsed MDS have been treated to draw definite conclusions. However, some patients respond, and given the high mortality associated with alternative procedures such as second BMT, donor MNC infusions are a reasonable approach for relapsed acute leukemia and MDS after allogeneic BMT.

Acute Disease↗
PubMed1995

Adoptive immunotherapy for relapsed leukemia following allogeneic bone marrow transplantation.

Donor mononuclear cell (MNC) infusions provide a very potent and effective anti-leukemic therapy. For patient's with CML who relapse after allogeneic BMT, the administration of donor MNC can result in a direct GVL effect and re-establish sustained remissions, even when assessed by very sensitive PCR-based techniques. The GVL reaction appears to be most prominent in patients with chronic phase CML. It is less apparent for patients with more advanced stages of CML or for patients with relapsed acute leukemia and myelodysplasia, although only small numbers of these patients have been treated. While the majority of patients tolerate this therapy very well, treatment related morbidity and mortality is still quite significant, and efforts to limit the severity of GVHD, and to recognize and treat marrow aplasia early may be useful. Longer follow-up of patients who have achieved complete remission will be required to determine if this therapy will have an impact on long term disease free survival, but at the current time, it would seem to be a very acceptable alternative to a second BMT.

Bone Marrow Transplantation↗
PubMed1994

Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia.

BACKGROUND: The ability of allogeneic bone marrow transplantation to cure chronic myeloid leukemia (CML) is due to both the conditioning regimen and the antileukemic effects of the lymphocytes in the grafted marrow. We studied the ability of interferon alfa-2b and infusions of mononuclear cells from the marrow donor to induce a graft-versus-leukemia reaction in patients with CML in relapse after bone marrow transplantation. METHODS: Eleven patients with relapsed CML after allogeneic bone marrow transplantation were treated with interferon alfa-2b and infusions of mononuclear cells. The patients were monitored for toxic effects, for hematologic and cytogenetic responses, and, with use of the polymerase chain reaction, for elimination of cells containing the bcr/abl messenger RNA transcript characteristic of the leukemic cells. RESULTS: Six of the eight patients with stable CML after relapse had complete remissions according to molecular genetic criteria, since no cells with bcr/abl messenger RNA transcripts were detected (the method can identify 1 leukemic cell among 1 million normal cells). The three patients with accelerated CML after relapse did not enter remission. Myelosuppression was prominent in eight patients. Grade I acute graft-versus-host disease (GVHD) occurred in six patients, and grade III acute GVHD occurred in three. Limited chronic GVHD developed in five patients. CONCLUSIONS: The induction of a graft-versus-leukemia reaction with interferon alfa-2b and infusions of donor mononuclear cells in patients with CML in relapse after bone marrow transplantation is an effective antileukemic therapy that may offer an alternative to a second marrow transplantation.

Adult↗
PubMed1983

Effect of calcium infusion on heart function.

The effects of calcium on heart function were studied in ten critically ill hypocalcemic patients (Ca++ = 1.93 +/- 0.08 mEq/L SD). Total calcium (TC), Ca++, blood pressure (MAP), venous pressure (CVP), pulmonary wedge pressure (PWP), cardiac output (CO), heart work (LVSW), systemic resistance (SPR), and pulmonary resistance (PVR) were measured before, during (15 and 30 minutes), and after (60 minutes) a 30-minute infusion of 1 gm CaCl2 (13.7 mEq). Calcium chloride infusion increased Ca++ significantly at 15 and 30 minutes (2.2 +/- 0.25 mEq/L) and remained elevated at 60 minutes (2.12 +/- 0.24). Cardiac output and LVSW rose at 15 minutes (9.4 leads to 10.6 L/min; 98 leads to 115 gm-m) but fell to below preinfusion levels by 60 minutes (8.9 +/- 2.0 L/min and 92 +/- 30 gm-m, respectively). These data show that calcium infusion for hypocalcemia does not provide meaningful improvement in cardiovascular function and is best avoided unless left heart function is closely monitored.

Calcium Chloride↗