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Biomedical subjects

S Jootar

Publications and source records attributed to S Jootar.

At least 19 recordsLinked to original sources

Ongoing challenges of a global international patient assistance program.

The Glivec International Patient Assistance Program (GIPAP) that is supported by Novartis Oncology provides Glivec (imatinib), an innovative oral therapy for chronic myelogenous leukemia and gastrointestinal stromal tumours, at no cost to patients in developing countries who could otherwise not afford treatment. Using a novel direct-to-patient approach this program is currently successfully providing Glivec to underserved patients in 81 countries. A number of challenges were faced in the implementation of this program in countries where cancer is not a priority, and where the healthcare and other infrastructure can be very limited. By working within the existing healthcare system of each country, and with any national cancer control programme that may be in place, through careful selection of qualified institutions and physicians, while maintaining a global approach to ensure consistency and quality, GIPAP has become an efficient and sustainable access program. Novartis has made a long-term commitment to GIPAP, and is currently exploring new patient access programs for other drugs.

Administration, Oral↗

Outcome of transplantation with unrelated donor bone marrow in children with severe thalassaemia.

SUMMARY: We conducted a study of unrelated donor bone marrow transplantation (BMT) in 11 children with severe thalassaemia. The conditioning regimen consisted of busulphan, cyclophosphamide and antilymphocyte globulin. All received T-cell nondepleted bone marrow. The median marrow-nucleated cell dose was 4.9 x 10(8) /kg (range; 3.5-8.0 x 10(8) /kg). Median time of granulocyte recovery was 16 days (range; 13-21 days), and of platelet recovery was 39 days (range; 14-196). Grade 2-4 acute graft-versus-host disease (GVHD) developed in six patients (54%), and grade 3-4 in one patient (9%). Three (27%) of 11 evaluable patients had chronic GVHD (limited stage). All 11 patients are alive without thalassaemia after a median follow-up time of 397 days (range; 171-814 days). This study lends support to consideration of unrelated donor BMT as an acceptable therapy to cure severe thalassaemia especially in patients who are young and do not yet show irreversible severe complications of iron overload.

Age Factors↗

Successful treatment of refractory autoimmune haemolytic anaemia in a post-unrelated bone marrow transplant paediatric patient with rituximab.

Here, we report a case of paediatric beta-thalassaemia major patient who underwent unrelated T cell-non- depleted bone marrow transplantation and developed a complication of autoimmune haemolytic anaemia (AIHA) refractory to corticosteroid and intravenous immunoglobulin therapy. After this child received two doses (375 mg/m2/dose) of rituximab (anti-CD20 monoclonal antibody), his AIHA was resolved.

Anemia, Hemolytic, Autoimmune↗

Full chimerism in nonmyeloablative stem cell transplantation in a beta-thalassemia major patient (class 3 Lucarelli).

Bone marrow transplantation is the only therapeutic option that can eliminate thalassemic disease. Early results indicated that children in class 3 Lucarelli had a much worse outcome because of high nonrejection mortality and high rejection rate. We therefore tried to investigate a nonmyeloablative stem cell transplantation (NST) approach for such a disease in order to reduce mortality and rejection. We report here the case of successful NST in a 10-year-old girl who had class 3 Lucarelli beta-thalassemia major. The conditioning regimen consisted of busulfan, fludarabine, antilymphocyte globulin and total lymphoid irradiation. Her GVHD prophylaxis included mycophenolate mofetil and cyclosporin. The patient had full donor engraftment without acute and chronic GVHD. She is now alive and well and remains disease-free 1 year after transplant.

Bone Marrow Transplantation↗

Effect of G-CSF on peripheral blood progenitor cell mobilization and collection from healthy donors.

We studied granulocyte colony-stimulating factor (G-CSF) mediated peripheral blood progenitor cells (PBPC), which were mobilized and collected from healthy donors for allogeneic transplantation. A total of 26 donors, age ranged from 21-41 years were mobilized with G-CSF at a dose of 7.5 microg/kg/day subcutaneously for 5 days and the collection was started on day 5. The CD34 cell counts reached a maximum on day 5 and subsequently declined despite continually given G-CSF. White blood cells (WBC), absolute neutrophil counts (ANC), absolute lymphocytes (AL) and their subsets, absolute mononuclear cells (AMNC), colony-forming unit-granulocyte, macrophage (CFU-GM) and CD34+ cells were increased about 6, 9, 2, 3, 34 and 40-fold, respectively, but red blood cells (RBC), hematocrit (Hct) and platelets (Pit) decreased on day 5 when compared to day 0. All parameters decreased after stem cell collection. For stem cell collection by Cobe Spectra, we used a blood volume of 19.27 +/- 4.65 liters, flow rate of 60.53 +/- 10.03 ml/minute, acid citrate dextrose solution (ACD)/blood ratio of 1:13.31, the final product volume was 314.14 +/- 72.24 ml, collection time was 325.40 +/- 73.36 minutes and one or two procedures were sufficient. The correlation between the number of CD34+ cells/kg, CFU-GM/kg and MNC/kg found in the harvested product and CD34 cells can be used for determining the necessary amount of progenitor cells for transplantation.

Adult↗

Allogeneic stem cell transplantation in a patient with refractory Burkitt's lymphoma using non-myeloablative conditioning regimen.

We have performed an allogeneic stem cell transplant in an 18-year-old male patient who had Burkitt's lymphoma. The patient had disease which was refractory to conventional intensive chemotherapy and radiation therapy. High-dose chemotherapy with autologous stem cell rescue was given but the patient relapsed within 2 months after transplantation. He was then treated with allogeneic stem cell transplantation using a fludarabine, busulfan and anti-thymocyte globulin-based conditioning regimen. His GVHD prophylaxis included mycophenolate and tacrolimus. The patient had engraftment within 14 days. Investigation by FISH showed more than 95% of his peripheral blood nucleated cells to be of donor origin since day +14. He is now alive and well and remains disease-free 6-months after the transplant. A graft-versus-lymphoma effect is thought to be one of the factors contributing to his remission.

Adolescent↗

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Antineoplastic Combined Chemotherapy Protocols↗

Amifostine and hematologic effects.

Amifostine is a protective agent of normal tissue from adverse effects of radiochemotherapy. It is the prodrug that is dephosphorylated by alkaline phosphatase on plasma membrane into the active form named WR-1065. More than 90 per cent of the drug is cleared from plasma in 6 minutes and the peak tissue concentration is 10-30 minutes after intravenous administration. Amifostine has the selective property to protect normal tissue but not cancer cells by mainly scavenging free radicals induced by radiation and chemocytotoxic agents. Both preclinical and clinical studies of this drug provide the significant protection of hematopoietic progentitors from a broad range of cytotoxic agents such as cyclophosphamide, cisplatin, vinblastine, carboplatin, mitomycin-C, fotemustine, doxorubicin, daunorubicin and radiation as well. Moreover, this drug can protect other normal organs or tissues including kidney, salivary gland, liver, heart, lung and small intestine. Amifostine is quite safe, the two major side effects are vomiting and hypotension, and the minor effects are flushing, sneezing, dizziness, chills, metallic taste etc. The drug was approved by the FDA of U.S.A. for use as a cytoprotectant in cyclophosphamide and cisplatin treatment for advanced ovarian cancer and non small cell lung cancer.

Amifostine↗

Etiology and incidence of thrombotic and hemorrhagic disorders in Thai patients with extreme thrombocytosis.

A retrospective study of 126 patients with extreme thrombocytosis (defined as a platelet count > or = 1,000 x 10(9)/L) was performed during a five-year period (June 1994-June 1999). The aim of this study was to determine the etiology and to evaluate the clinical consequences of extreme thrombocytosis. Seventy patients (55.5%) had reactive thrombocytosis (RT) with an age range of 43 +/- 2.2 years, 56 (44.5%) had chronic myeloproliferative disorders (MPD) with an age range of 53 +/- 2.4 years. Underlying causes of RT were malignancy (25/70 or 35.7%), infection (16/70 or 22.9%), postsplenectomized beta-thalassemia/Hb E (11/70 or 15.7%), inflammation (12/70 or 17.1%), iron deficiency anemia (6/70 or 8.6%). Duration post splenectomy in our beta-thalassemia/Hb E patients ranged from 4 months to 21 years, with a median of 10 years. Subtypes of our MPD cases were chronic myeloid leukemia (30/56 or 53.6%), essential thrombocytosis (18/56 or 32.1%), polycythemia vera (4/56 or 7.1%), agnogenic myeloid metaplasia (3/56 or 5.4%) and unclassified MPD (1/56 or 1.8%). Bleeding and thrombotic tendency were respectively noted in 7 (12.5%) and 2 (3.6%) of MPD patients. Two patients of the MPD group (3.6%) experienced both bleeding and thrombotic episodes. One patient (1.4%) of the RT group developed vasculitis-associated thrombosis. However, none of the patients in the RT group had bleeding complications. Extreme thrombocytosis was not a rare condition in a university hospital population, and bleeding and/or thrombotic complication was more common in the MPD group.

Adult↗

Preliminary study of HLA-ABCDR antigens in CML, ANLL, thalassemia and severe aplastic anemia in Thais.

The objective of this study was to analyse human leukocyte antigen (HLA) and disease association in common blood diseases [chronic myelogenous leukemia (CML), acute nonlymphocytic leukemia (ANLL), thalassemia and severe aplastic anemia] in Thais. The subjects were patients from the Hematological Clinic, Departments of Medicine and Pediatrics, Ramathibodi Hospital who were referred for HLA typing for bone marrow transplantation (BMT) at the Histocompatibility Laboratory from March 1988 to September 1997. A total of 129 patients had complete HLA-ABC typing. The patients included 45 CML, 40 ANLL, 26 thalassemia (Thal) and 18 severe aplastic anemia (SAA). Of these, 88 patients were typed for HLA class II. The HLA class I (ABC) and II (DR, DQ) typings were performed by microlymphocytotoxicity test. It was found that HLA class I was associated with CML, ANLL and Thal, whereas, HLA class II was associated with SAA. HLA-B8 and HLA-B18 were increased in CML with R.R. values of 12.2 and 3.9, respectively, whereas, HLA-B18 was increased in ANLL with R.R. value of 4.5. In addition, HLA-DR2 and DR3 were increased in SAA with R.R. values of 3.8 and 4.8, respectively. For Thal, HLA-A2 and B46 were increased in Thal in Central Thais with R.R. values of 3.3 and 6.1, respectively, whereas, HLA-B13 was increased in Thal in Northern Thais with R.R. value of 8.5. On the other hand, HLA-B7 was absent in CML. HLA-Cw7 was decreased in CML and SAA, whereas, HLA-DR6 was decreased in ANLL and SAA. Furthermore, HLA-Cw6 was also decreased in CML, whereas, HLA-A33 and Bw4 were decreased in SAA. Although the sample size of each disease was small, the increase of HLA-DR2 was observed in SAA in Thais which was similar to other studies in different ethnic groups. These preliminary data may be useful for further study in HLA and blood disease association.

Adult↗

High dose chemotherapy and peripheral blood stem cell transplantation for high risk primary breast cancer: a single center experience in Thailand.

Twenty patients with high risk primary breast cancer underwent a high dose chemotherapy program at Ramathibodi Hospital, Bangkok. Eligible patients included 21 women who had a histological diagnosis of breast cancer with more than 10 axillary lymph nodes involved. The patients first underwent modified radical mastectomy, followed by conventional doxorubicin containing adjuvant chemotherapy, before entering the treatment program. Peripheral blood stem cells were mobilized with cyclophosphamide and G-CSF and were harvested by leukapheresis. High dose chemotherapy consisted of cyclophosphamide 5,625 mg/m2, cisplatinum 165 mg/m2 and carmustine (BCNU) 600 mg/m2 were subsequently given, followed by infusion of the harvested peripheral blood stem cells. The median duration of cytopenia after transplantation was 8 days (range 7-12). The median expense for the transplantation, in addition to the cost of mastectomy and conventional chemotherapy, was 224,396 Baht (approximately US $5,350). Three out of the first four patients developed interstitial pneumonitis within three months after transplantation. There was one fatal case which was the only regimen related mortality. BCNU was then reduced to 450 mg/m2 and lung complications were markedly reduced afterwards. The median follow up time was 37 months with a median disease free survival of 38 months and overall survival of four years at 84%.

Adult↗

Quality of life in Thai patients after bone marrow and peripheral blood stem cell transplantation: a comparison study with patients treated with conventional chemotherapy.

This study of adult patients of Thai cultural background compared the quality of life (QOL) of patients undergoing bone marrow and peripheral blood stem cell transplantation (BMT/PBSCT) with that of patients treated with conventional chemotherapy (CT). The study population comprised 59 patients who were transplant recipients (29 allogeneic, 29 autograft, and one syngeneic BMT/PBSCT) and 24 patients treated with CT for various hematologic malignancies. The participants completed a 50-item structured QOL questionnaire sent by mail. No significant differences were found between the two patient groups regarding their psychological, social, and treatment-related well-being or their overall QOL; all scores were above 75% of the total. The mean score regarding the physical domain, however, was significantly lower in BMT/PBSCT patients. Areas of highest concern in both groups were sexuality and financial burden. Happiness, functional ability, financial burden, and the degree of familial acceptance were the most important predictors of the self-rated QOL in BMT/PBSCT patients. Seventy-five percent of BMT/PBSCT patients would be willing to undergo the procedure again under the same circumstances. These results indicated that the QOL of Thai patients undergoing BMT/PBSCT was in general satisfactory and comparable to patients treated with conventional CT.

Adolescent↗

Delayed administration of G-CSF in both mobilization and post transplantation in autologous peripheral blood stem cell transplantation.

Granulocyte colony stimulating factors (G-CSFs) play a very important role in the current technique of stem cell transplantation. The conventional timing of administration of G-CSF in both mobilization and post transplantation has been right after chemotherapy or right after transplantation. We have studied the effects of timing of administration of G-CSF in 21 patients who had autologous stem cell transplantation for breast cancer, lymphoma or nasopharyngeal cancer. Their stem cells were mobilized by chemotherapy followed by G-CSF, which were given on day +1 or day +5 after chemotherapy. The median peak percentage of CD34 positive cells harvested using both technique were 1.88 and 0.48% respectively. After transplantation, G-CSF were given on day +1 or day +6 after stem cell infusion until neutrophil recovery. The time until bone marrow recovery was significantly longer in the group with delayed administration of G-CSF (10 days versus 8 days). However, there was no difference in duration of neutropenic fever or hospital stay after transplantation. The transplantation outcome was also unaffected. We therefore concluded that G-CSF can be given in the delayed fashion in both mobilizing and post transplantation settings without jeopardizing the outcome and this would result in a significant cost saving.

Adult↗

Study of hematopoietic progenitor cells, hematological values and lymphocyte subsets in cord blood: application for cord blood transplantation.

Hematological values, lymphocyte subsets and hematopoietic progenitor cells from normal term cord blood samples were studied, compared with normal adult blood, and analysed to determine whether a single collection of cord blood is sufficient for transplantation in adults. The parameters were assayed by automatic cells counter, flow cytometry and semisolid cell culture. All of the hematological values except RBC and MCHC were higher than in normal adult blood. Sex had an influence on RBC, Hb, Hct, Plt and reticulocyte counts. For lymphocyte subsets, all of the absolute CD3+, CD4+, CD8+ counts and T helper: suppressor ratio were higher than those of adult blood. All of the hematopoietic progenitor cells in cord blood were also higher than in adult blood. The mean volume of cord blood for each collection was 80.75 +/- 4.81 ml and the mean numbers of nucleated cells, CFU-GM and CD34+ were 13.51 +/- 0.38 x 10(8) cells, 4.33 +/- 0.66 x 10(5) colonies and 42.65 +/- 7.00 x 10(5) cells respectively. This 80 ml of cord blood would contain sufficient marrow repopulating cells for a recipient weighing about 20 kg. Recently developed technology, including ex vivo expansion may even permit transplants in adults.

Adult↗

Serum erythropoietin levels in thalassemia major and intermedia.

Serum erythropoietin (EPO) levels were determined by enzyme linked immunosorbent assay (ELISA) in 61 thalassemic patients, consisting of 23 thalassemia major (TM) patients with multiple transfusion, 38 patients with thalassemia intermedia (TI). Thirty-two normal controls were also studied. The mean serum EPO levels were significantly higher in both groups with TM (165.96 +/- 17.31 mlU/ml) and TI (126.43 +/- 50.56 mlU/ml) compared with the control group (8.33 +/- 3.91 mlU/ml). The mean value of hematocrit (Hct) in the patients with TM (18.70 +/- 3.51%) was lower than those with TI (25.24 +/- 4.19 %) whereas the mean serum EPO level were significantly higher in TM than TI patients. An inverse correlation between the serum values of EPO and Hct was observed in both TI and TM patients, however this correlation was significant only in TI (r = -0.61, p<0.001). These data showed that serum EPO levels increased in all thalassemia patients despite repeated transfusion. Multiple transfusion may modulate the response of serum EPO to the degree of anemia, resulting in increased EPO levels and independent anemia in the TM patients.

Adolescent↗

Myelodysplastic syndromes in Thailand: a retrospective pathologic and clinical analysis of 117 cases.

To gain more insight into the understanding of myelodysplastic syndromes (MDS) as they occur in Thailand, a retrospective clinicopathologic analysis was conducted in patients (age > 15 years) diagnosed as MDS from January 1992 to December 1996 at the five major medical centers in various geographic regions of the country. The central reviewers independently examined the bone marrow and peripheral blood smears of all the patients and classify the disease according to the French-British-American (FAB) classification. There were a total of 117 eligible patients. The median age of the patients was 56 years (range 16-86). The male:female ratio was 1:1. Thirty-two percent of the patients were younger than 40 years. The frequency of the FAB subtypes was RA/RARS, 54.7; RAEB, 23.1; CMML, 9.4; and RAEB-T, 12.8%. Anemia was the most common symptom presenting in 84.6% of the patients. In the 34 patients in whom the cytogenetics in the bone marrow were analysed, 44.1% revealed abnormalities. Of these, monosomy 7 and trisomy 8 were the most common aberration, each being detected in 26.7% of the patients. Transfusions were the main therapeutic modality in 80% of the patients. Kaplan-Meier analysis revealed a 5 year survival rate of 29% for the whole group with a median survival of 24 months. Twenty-five percent of the patients had progressed to acute myelogenous leukemia (AML) with a median time to disease-progression of 23 months. The median survival for RA/RARS, RAEB, CMML and RAEB-T were 58.4, 19.9, 10.7 and 8.7 months, respectively (P < 0.001). The stepwise Cox regression analysis revealed the percentage of blasts in the bone marrow as the only parameter significantly associated with survival and disease progression. On comparison with data from other countries, the age of Thai patients with MDS is considerably lower than the western population but is comparable to other asian countries. The distribution of the FAB subtypes and the survival of the patients are similar. The major prognostic features, however, lie in the percentage of blasts in the bone marrow rather than the degree of the observed cytopenia.

Adolescent↗