Changes of immunological markers after autologous peripheral blood stem cell transplantation

PURPOSE: Recently high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. METHODS: Immunological parameters were examined before and after PBSCT in 9 patients with lung cancer and 13 patients with malignant lymphoma. Findings were compared with those for bone marrow transplantation (BMT). Peripheral blood cells were analyzed for phenotype and the levels of cytokines and soluble factors were measured. RESULTS: After PBSCT, activated T cells (CD3+HLA-DR+ cells, CD8+HLA-DR+ cells) and suppressor/cytotoxic T cells (CD8+CD11b- cells) were significantly higher in the patients with lung cancer than in those with malignant lymphoma. Serum levels of interleukin-4 and soluble interleukin-2 receptor were also significantly higher in the patients with lung cancer than in those with lymphoma. On the other hand, the serum levels of interferon gamma, tumor necrosis factor alpha, interleukin-6, soluble human leukocyte antigen class 1, and soluble thrombomodulin were significantly increased after bone marrow transplantation. The transfused peripheral stem cells of lung cancer and lymphoma patients had a similar number of granulocyte/macrophage-colony-forming units, but lung cancer patients had significantly more CD34-positive cells. CONCLUSION: By reinfusing large numbers of autologous immune cells, PBSCT may accelerate immune reconstitution, with T cells being likely to have a marked therapeutic potential. The changes after PBSCT were greater in patients with lung cancer than in lymphoma patients. These blood cells are potent mediators of anticancer activity and could play an important role in the elimination of autologous malignant cells.     

Hemolytic uremic syndrome after allogeneic or autologous hematopoietic stem cell transplantation for childhood malignancies

To identify structural features important for low temperature activity in archaeal proteins, elongation factor 2 (EF-2) genes (aef2) were sequenced from psychrophilic, mesophilic and thermophilic methanogens. Scatter plots were used to compare evolutionary distances for EF-2 amino acid sequences vs. 16S-rRNA sequences from methanogens growing at diverse temperatures. The absence of a temperature bias for the rate of protein vs. nucleic acid evolution demonstrated the importance of comparing closely related proteins in order to identify changes indicative of thermal adaptation. Three-dimensional modelling of the new EF-2 sequences enabled the identification of amino acid residues that may be important for conferring low temperature activity and included greater structural flexibility produced by fewer salt bridges, less packed hydrophobic cores and the reduction of proline residues in loop structures.     

Influence of marrow erythropoietic activity on serum erythropoietin levels after autologous hematopoietic stem cell transplantation

BACKGROUND AND OBJECTIVE: Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after conditioning for autologous stem cell transplantation (ASCT) before progressively returning to adequate levels. We investigated the possible influence of erythropoietic activity on these observations. DESIGN AND METHODS: Forty patients undergoing an ASCT, 8 with bone marrow (BMT) and 32 with peripheral blood stem cells (PBSC), were separated into 3 groups. Group 1 was formed of the 8 BMT patients (median time to 1% reticulocytes: 39 days), group 2 of 16 PBSC patients with relatively slow erythroid engraftment (> or = 15 days to 1% reticulocytes, median 19 days) and group 3 of 16 PBSC patients with prompt erythroid recovery (< 15 days to 1% reticulocytes, median 13 days). Marrow erythroid activity was assessed by serum transferrin receptor levels (sTfR). Serum Epo (sEpo) levels were expressed in relation to the degree of anemia as observed/predicted (O/P) ratios of (O/P) log (sEpo). RESULTS: Serum sTfR levels decreased by more than 50% in all 3 groups after conditioning, reaching their nadir on day 7. Nadir values doubled by day 28 in group 3, day 60 in group 2, but not within 100 days in group 1. O/P sEpo ratios increased inappropriately in all 3 groups after conditioning but then declined at very differing speeds in the 3 groups. In group 1, ratios remained above 1.10 through to day 28 and above 1.00 through to day 42, before leveling off at around 1.00 thereafter. In group 2, ratios remained above 1.00 through to day 14, than decreased to a minimum of 0.89 by day 42 before returning to 1.00 by day 100. In group 3, ratios decreased to 0.84 by day 21 and remained below 0.90 thereafter. INTERPRETATION AND CONCLUSIONS: We conclude that sEpo levels are not only influenced by tissue oxygenation but also depend on the mass of erythroid precursors in the bone marrow. This may be the main explanation for the observed changes in sEpo levels during ASCT.     

Immune reconstitution after autologous progenitor hemopoietic cell transplantation. A study comparing autologous bone marrow and autologous peripheral blood transplantation

BACKGROUND: In order to find out the effect of peripheral blood (PB) hematopoietic progenitor cells on immune reconstitution the present study compares, through a randomized trial, some lymphoid subsets after peripheral blood (PBT) or bone marrow (BMT) autologous transplantation. MATERIAL AND METHODS: Twelve patients suffering from malignant hematological disorders were included (6 BMT and 6 PBT). From these patients 14 lymphoid and natural killer (NK) subsets were sequentially analyzed using appropriate dual staining. NK activity was analyzed by measuring Cr51 release from the K562 cell line. Studies were done in days and -6, +10, +17, +24, +31, +38, +52, +66, +90, +120, +180 and +360 after transplantation. RESULTS: The CD8+ cell regeneration was produced mainly by activated cells (CD38+), and no differences were observed between BMT and PBT, but CD8+ HLADR+ cells were higher in the PBT group. During the first year after transplantation CD4+ lymphoid cells were never within normal range, and its recovery was due to the memory subset (CD4+/CD45RO+). The CD19+ lymphocytes began their regeneration after the first month and it was produced mainly by by the CD19+/CD5+ subset. NK cells recovered faster in patients who underwent PBT, but NK activity was similar in both subgroups of patients and it was within normal range from day +17 until the end of the study. CONCLUSION: T, B and NK lymphoid reconstitution do not differ significantly between patients that receive BM or PB as hemathopoietic rescue, but PB seems influence a faster reconstitution of cytotoxic subsets (CD8+/HLADR+ and NK lymphoid cells).     

Remission of nonerosive polyarthritis associated with Sj?gren's syndrome after autologous hematopoietic stem cell transplantation for lymphoma

We describe a 50-year-old woman with seropositive rheumatoid arthritis and Sj?gren's syndrome who underwent autologous blood stem cell transplantation after relapse of associated non-Hodgkin's lymphoma. This resulted in complete remission not only of the lymphoma, but also the arthritis.     

Aerobic exercise in the rehabilitation of cancer patients after high dose chemotherapy and autologous peripheral stem cell transplantation

BACKGROUND: Fatigue and loss of physical performance are frequent problems of cancer patients. In a pilot study, the authors evaluated the feasibility and effects of aerobic training in the rehabilitation of cancer patients after completing high dose chemotherapy. METHODS: Sixteen patients participated in a specially designed rehabilitation program for 6 weeks. The patients entered the program, which consisted of walking on a treadmill, shortly after completing treatment. Sixteen patients who did not train served as controls. Physical performance (maximum speed on the treadmill test), cardiac function, and hemoglobin concentration were compared at the time of discharge from the hospital and 7 weeks later. At the second examination, fatigue and limitations in daily activities due to impaired endurance were assessed during personal interviews. RESULTS: At the time of discharge from the hospital, maximum physical performance (training group: 6.2 +/- 1.1 km/hour; controls: 6.2 +/- 1.3 km/hour) and hemoglobin concentration (training group: 10.1 +/- 1.4 g/dL; controls: 10.1 +/- 1.2 g/dL) were similar for both groups. After 7 weeks, improvement in maximum physical performance (training group: 8.3 +/- 1.6 km/hour; controls 7.5 +/- 1.3 km/hour) and hemoglobin concentration (training group: 13 +/- 1 g/dL controls: 12 +/- 1.4 g/dL) were significantly higher for the training group (P < 0.05). By the second examination, no patient in the training group but 4 controls (25%) reported fatigue and limitations in daily activities due to low physical performance. CONCLUSIONS: Aerobic exercise improves the physical performance of cancer patients recovering from high dose chemotherapy. To reduce fatigue, this group of patients should be counseled to increase physical activity rather than rest after treatment.     

High-dose chemotherapy with autologous peripheral blood stem cell transplantation for metastatic gastric leiomyosarcoma

We report a case of metastatic gastrointestinal leiomyosarcoma treated with high-dose combination chemotherapy and autologous peripheral blood stem cell transplantation. After incomplete surgical resection, enteral, peritoneal and hepatic involvement remained. Postoperatively, standard-dose chemotherapy with etoposide, ifosfamide, cisplatin and epirubicine, and high-dose chemotherapy with the same agents (carboplatin replacing cisplatin) was given. Treatment was well tolerated and the patient remains in complete remission at 36+ months. We conclude that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation may be of use as treatment for inoperable residual disease after resection of the primary lesion in gastrointestinal and other soft tissue sarcomas.     

Studies with high-dose chemotherapy and subsequent autologous stem cell transplantation in breast carcinoma

Survival rates for several subgroups of patients with breast cancer treated with conventional therapy remain poor. Only about 30% of patients with primary breast cancer involving more than 9 axillary lymph nodes remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy and radiotherapy. Metastatic breast cancer with 5 year survival rates of about 3% generally represents incurable disease. Chemotherapeutic agents are conventionally limited by side effects. The easy procurement of haematopoietic stem cell support through mobilization of peripheral blood progenitors has spurred the development of new strategies employing high-dose treatment for treatment of high risk breast cancer. Autologous stem cell support antagonizes chemotherapy-induced myelotoxicity and thereby allows dose escalation by a factor of 1.5 to about 20. Pilot studies evaluating significant dose escalation in adjuvant treatment of patients with advanced disease have resulted in an apparent improvement in event-free survival rates to over 70%. Repetitive applications of chemotherapy at myeloablative doses are now increasingly being used. Data from prospectively randomized phase III trials will not be available before the end of 1998. For metastatic breast cancer one prospective, randomized clinical trial has been published. Results are significantly better for patients who have been treated by high-dose chemotherapy compared to patients who received conventional polychemotherapy (median survival 90 vs. 45 weeks). For methodological reasons (small patient numbers, patient selection, weak standard therapy etc.) results from the trials cited above are under discussion. Until publication of further results from ongoing phase III trials HDC for breast cancer remains experimental and should not be given outside of clinical trials.     

Plasma cell leukemia 3 months after autologous blood cell transplantation for multiple myeloma

A case of an amebic liver abscess with unusual clinical manifestations is presented. A middle-aged male with an abscess in both lobes of the liver presented with obstructive jaundice due to pressure on the porta hepatis with stasis of the bile in the intrahepatic biliary radicals. The patient did not respond to repeated needle aspirations and thus required open drainage. Subsequently, the patient developed a biliary leak through the drainage sites, and an injection of contrast dye into the cavity revealed a communication between the abscess cavities and the biliary tree. The biliary leak stopped spontaneously, and the large cavities also closed completely during the followup period.     

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy

Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease. The coexistence of autoimmune disease and hematologic malignancy provides an opportunity to examine the response of autoimmune disease to ABMT or ASCT. We describe 4 patients with autoimmune disease (3 with psoriasis and 1 with rheumatoid arthritis) and hematologic malignancy. In each patient, the autoimmune disease remitted posttransplantation, but, in 4 patients with long-term followup, it recurred at 8-24 months. The earliest relapse occurred in a patient treated with interferon-alpha. Our experience suggests that a single autograft with unpurged stem cells is unlikely to cure autoimmune disease, but that other strategies building on this approach are worthy of investigation.     

Prognosis of hematological patients with relapse following high-dose chemotherapy and autologous stem cell transplantation

A retrospective analysis of the outcome for 283 haematological patients who relapsed after high dose chemotherapy and autologous stem cell transplantation during a five year period from 1989 to 1994 is presented. The patients were treated in accordance with local regimes at 20 Nordic transplantation centers and included patients with acute leukemia (157 patients), multiple myeloma (16 patients) and lymphoma (110 patients). Two hundred and twenty-nine patients with relapse or progressive disease were given chemo- and/or radiotherapy and the response was evaluated after 90 days. Fifty-four patients (24%) obtained a complete remission and 44 patients (19%) partial remission. The overall median survival after relapse was five months. In the group who received salvage treatment the median survival was seven months, and for the 54 patients in complete remission the median survival was 15 months. We found that survival after relapse depends upon primary disease, the time from transplantation to relapse and whether salvage therapy was initiated.     

Malignancy-associated remission of systemic lupus erythematosus maintained by autologous peripheral blood stem cell transplantation

Many investigators worldwide are currently exploring the role of peripheral blood stem cell transplantation (PBSCT) in managing autoimmune diseases. We report the case of a woman with systemic lupus erythematosus (SLE) with mucocutaneous and renal involvement, who underwent PBSCT for stage IVB Hodgkin's disease. Following the development of the lymphoma, she has had a prolonged clinical and serologic remission of the SLE. The potential effects of lymphoproliferative disorders and PBSCT on the course of SLE are considered.     

Pneumoperitoneum without peritonitis after allogeneic peripheral blood stem cell transplantation

Allogeneic blood stem cell transplantation is associated with multiple complications. We report a case of pneumoperitoneum without peritonitis associated with colonic pneumatosis in a patient who had undergone an allogeneic peripheral blood cell transplant     

Trichomonas foetus meningoencephalitis after allogeneic peripheral blood stem cell transplantation

The authors report a case of adrenal metastasis contralateral to a renal cell carcinoma in a 74-year-old patient who had undergone right radical nephrectomy for renal cell carcinoma. Nine months later, computed tomography revealed a hypervascular mass considered to be an aneurysm of the splenic artery. Arteriography led to the diagnosis of hypervascular adrenal tumour. Left adrenalectomy was performed. Histological examination showed a metastasis from renal cell carcinoma. This is an unusual form of renal cancer metastasis. Its treatment and prognosis are discussed.     

Total parenteral nutrition on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation

The resting energy expenditure (REE) and the respiratory quotient (RQ) were measured longitudinally using indirect calorimetry to examine the effects of total parenteral nutrition (TPN) on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation (PBSCT). There were six children (two males and four females) and the age ranged from five to 13 years (median, eight yrs). The diagnosis included acute lymphocytic leukemia (ALL; 4), neuroblastoma (NBL; 1) and primitive neuroectodermal tumor (PNET; 1). TPN was started after the patients were stabilized following PBSCT (group A; n = 3) or before the initiation of high-dose cytoreductive chemotherapy (HCC) (group B; n = 3). Duration of HCC before PBSCT was identical between the two groups (six to eight days). Average total calorie and protein intake during HCC was significantly higher for group B than for group A. The %REE, the percentage of REE to the predicted basal energy expenditure (BEE), in group A showed 133 +/- 19%, 129 +/- 14% and 146 +/- 11% during three periods of HCC (days -8 to -1 of PBSCT), bone marrow suppression (days 0 to 11 of PBSCT) and bone marrow recovery (days 12 to 22 of PBSCT), respectively. In contrast, those in group B were 10% to 20% lower than those in group A at all periods. Carbohydrate oxidation rates during HCC in group A were significantly lower than those in group B, and those were not different between both groups during post-PBSCT periods. Fat oxidation rates in both groups were similar at all stages of periods. In contrast, protein degradation rates in group A were significantly higher than those in group B at all stages of the period. From these results, we concluded that commencement of TPN administration prior to HCC in the patients undergoing PBSCT provides beneficial effects to maintain better energy metabolic and nutritional status.