International Journal of Hematology-Oncology and Stem Cell Research
Volume:1 Issue: 1, Jan 2004

Intensive induction therapy-in acute myeloid leukemia (AML), as in some other systemic malignancies- is a strategy fundamentally different from post-remission strategies. Approaches like consolidation treatment, prolonged mainte nance, and autologous or allogeneic transplantation in the first remission are directed against minimal residual disease with a malignant cell population having survived the induction treatment. In contrast, induction therapy deals with naive tumor cells possibly different in their sensitivity from their counterparts in remission. Therefore, in AML it has been suggested to introduce intensification strategies into the induction part of treatment as a new step after the preceding intensification steps in the post-remission part. As expected from the dose effects observed in post-remission treatment using more AraC or longer treatment, similar dose effects have been found in the induction treatment both by the incorporation of high-dose AraC and by the double induction strategy administered in patients up to 60 years of age. For example, patients with poor risk AML due to an unfavorable karyotype, high LDH in serum, or delayed response, benefited from double induction containing high-dose AraC by a longer survival as compared to that from standard dose AraC. A corresponding dose effect in the induction treatment has been found in patients of 60 years and older receiving daunorubicin 60 vs 30 mg/m2 as part of the TAD regimen with higher dosage. This treatment significantly increased the response and survival rate in older patients who represented a poor risk group as a whole. Thus, we could demonstrate, both in younger and older patients, that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits a cumulative toxicity in that a repetition of courses containing high-dose AraC in the post-remission period is associated with considerable myelotoxicity leading to longlasting aplasias of about 6 weeks. However, after intensive induction treatment, high-dose chemotherapy in remission may become practicable using autologous stem cell rescue and may contribute to a further improvement of the outcome in poor risk as well as average patients with AML. These approaches are currently investigated by the German AMLCG. While there are clear limitations in the intensity of antineoplastic treatment for AML, as for other systemic malignancies, some further intensification may be possible and effective.

Maintenance treatment for patients with acute myeloid leukemia (AML) in remission has recently been controversially discussed and even abandoned by several groups. An analysis of 16 published multicenter trials, however, revealed the highest probabilities of relapse free survival (RFS) in the range of 35-42 % at 4-5 years only in patients assigned to maintenance treatment when adult age and intent-to-treat conditions were considered. After having demonstrated a superior RFS from 3 year maintenance following standard dose consolidation over that from consolidation alone (p<0.0001), the German AMLCG requestioned the effect of maintenance randomly compared with sequential high-dose AraC and Mitoxantrone (S-HAM) in patients having received intensified induction treatment. The RFS shows an advantage for maintenance with 32 % versus 25 % (p=. 021). We conclude that maintenance treatment continues to substantially contribute to the management of adult patients with AML, even as part of recent strategies using intensified induction treatment, and thus appears necessary in these settings.

Osteosarcoma is the most common bone sarcoma, and the third most common malignancy in children and adolescents. Before 1970, amputation was the sole treatment. Eighty percent of patients died from metastatic diseases, most commonly in the lungs. Over the past three decades, effective neoadjuvant (preoperative) and adjuvant (postoperative) chemotherapy protocols have improved the ability to perform limb salvage resections, disease free survival and overall survival rates.Patients and The study was conducted on 28 patients (15 male and 13 female) whose diagnoses were confirmed by excisional biopsy without any proof of metastasis in clinical and radiological assessments from September 2001 to November 2002. All patients were treated with three-drug regimen consisting of Adriamycin, Ifosfamide and Cisplatin. The neoadjuvant chemotherapy was administered in three courses. The first course, Ifosfamide (2gr/IV) and Adriamycin (75mg/m², IV infusion) were given on the first day and Ifosfamide (1.5 gr/m² by continuous infusion) alone for 6 days. The second course consisted of Adriamycin (75mg/m², IV infusion) and Cisplatin (100mg/m², IV infusion) for one day. The third course was the same as the first. After surgery, all patients received adjuvant therapy similar to the neoadjuvant protocol mentioned above. Limb salvage was the most common surgical method. The treatment outcome particularly depended on the percentage of tumor necrosis. Overall and disease-free survival were also measured. According to the tumor necrosis percentage, the tumor response to chemotherapy was classified from good to poor response. In this study, 63.6% of patients showed good response and 36.4% indicated poor or no response to chemotherapy. The tumor necrosis percentage was significantly correlated with age≤ 20 years (P= 0.01), tumor size ≤84 cm³ (P= 0.03) and the site of tumors in femurs (P= 0.03). The average follow-up time was 132 days, ranging from 15 to 618 days. The first year survival rate was 100%, and the disease-free survival (DFS) was 70.8% for the same time period. Disease-free survival was significantly correlated with the chemotherapy response (P= 0.03), which was 100% in the good response group in the first year. Although we had utilized bone grafts for substantially resected bones, local relapses were remarkably low (2 cases), so we suggest that this surgical method can be a proper alternative treatment for different types of expensive prosthesis in countries with low socioeconomic status.

Chronic graft versus host disease (cGVHD) is one of the most serious potential complications ofallogeneic bone marrow transplantation.Study design and We analyzed the incidence of cGVHD and its associated risk factors in a group of 161Iranian recipients of HLA-identical sibling transplants, with at least 90 days post-transplantation survival. In themajority of cases (n=73), cGVHD occurred in the first year after the transplant (median 273 days). The actualprobability of cGVHD within 1 year was 45.3±7% (CI 95%). In a univariate analysis, the most important risk factor was the type of transplant. Peripheral blood stem celltransplants (PBSCT) showed a significant increase in cGVHD compared with bone marrow transplants (BMT)(RR=2.34, p<0.001). In addition, male recipients were at a greater risk than female recipients (RR=2.08, p=0.004).Other risk factors were the presence of prior acute GVHD (RR=2.37, p=0.04) and the previous acute GVHD grade(p=0.03); The probabilities of cGVHD in patients with grade 0, Ι, ΙІ, ΙΙΙ, ΙV acute GVHD were 24%, 44.7%, 42.6%,56.8%, 64.3%, respectively. In a multivariate analysis, the only independent predictive factors for the development of cGVHD were the type of transplant (PBSC>BM, p<0.001) and male recipient (p=0.005). The survival rate was 88.8% and there was no significant difference in the probability of survival between BPSCT vs BMT (93.8% vs 86.6%, p=0.5).

Chronic graft versus host disease (cGVHD) is one of the most serious potential complications ofallogeneic bone marrow transplantation.Study design and We analyzed the incidence of cGVHD and its associated risk factors in a group of 161Iranian recipients of HLA-identical sibling transplants, with at least 90 days post-transplantation survival. In themajority of cases (n=73), cGVHD occurred in the first year after the transplant (median 273 days). The actualprobability of cGVHD within 1 year was 45.3±7% (CI 95%). In a univariate analysis, the most important risk factor was the type of transplant. Peripheral blood stem celltransplants (PBSCT) showed a significant increase in cGVHD compared with bone marrow transplants (BMT)(RR=2.34, p<0.001). In addition, male recipients were at a greater risk than female recipients (RR=2.08, p=0.004).Other risk factors were the presence of prior acute GVHD (RR=2.37, p=0.04) and the previous acute GVHD grade(p=0.03); The probabilities of cGVHD in patients with grade 0, Ι, ΙІ, ΙΙΙ, ΙV acute GVHD were 24%, 44.7%, 42.6%,56.8%, 64.3%, respectively. In a multivariate analysis, the only independent predictive factors for the development of cGVHD were the type of transplant (PBSC>BM, p<0.001) and male recipient (p=0.005). The survival rate was 88.8% and there was no significant difference in the probability of survival between BPSCT vs BMT (93.8% vs 86.6%, p=0.5).

Thalassemia is probably the most common single gene disorder causing a major public health problem in the world. Currently, allogenic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for thalassemia. One major limitation of HSCT is the lack of HLA-identical sibling donors, so attention has turned to finding phenotypically matched unrelated donors.Patients and From 1991 to 2002, 182 thalassemia patients referred to our center for HSCT. Donor selection was based on HLA class I and class II histocompatibility matching. The results of the serologically HLA class I typing of 549 subjects (patients and their families) and HLA class II typing of 182 patients were compared with HLA class I and II antigens of 100 healthy Iranians normal people. The comparisons between these two groups were tested in univariate analysis, using the Pearson chi-squared statistics. In comparing, thalassemic families (549 subjects) and healthy Iranians (100 subjects) for HLA class I antigens, significant differences for 11 antigens, including A9 (p= 0.029), A11 (p= 0.01), A19 (p= 0.000), B16 (p= 0.000), B17 (p= 0.029), B27 (p= 0.003), B41(p= 0.000), C2 (p= 0.015), C3(p= 0.012), C4 (p= 0.004), C7 (p= 0.000) were found. For HLA class II antigens, we found that only HLA-DR7 was significantly different (p= 0.002) between 182 thalas-semia patients and the healthy Iranian normal group. In this study, we found that thalassemia families showed significant differences, compared to the healthy Iranian group in several HLA antigens. Comparing HLA polymorphism and finding enough similarity in thalassemia families in the countries, located in the thalassemia belt, may provide benefits for establishing a common HLA bank of thalassemia families.

Engraftment by donor lymphocytes in an immunologically compromised host can result in donor T-cell activation against host major histocompatibility complex antigens, with resultant GVHD.The acute form of GVHD (aGVHD) is characterized by erythroderma, cholestatic hepatitis, and enteritis. The intestinal symptoms of aGVHD include crampy abdominal pain and watery diarrhea, often with blood. The conditioning regimen and infectious agents may produce similar symptoms. Severe intestinal aGVHD is a life-threatening event and associated with high mortality.In this case report, we describe two patients with major thalassemia who experienced acute gastrointestinal GVHD. One of them experienced it after peripheral blood transplantation at day +13, and the other after bone marrow transplantation at day +14. The first presentation was severe GI bleeding, and then 2 litters per day diarrhea. Besides standard prophylaxis with Cyclosporine and Methotrexate, Methylprednisolone 2mg/kg per day commenced because GI bleeding started and afterward supportive treatment means were continued. Following administration of Methylprednisolone, the amount of GI bleeding and diarrhea declined; in addition, the need for whole blood transfusion and blood products decreased. Both children had no problem in follow-up.Engraftment evaluation by the VNTR method showed 100 percent validity. GI bleeding after transplantation can be a major presentation of aGVHD, which requires precise attention, and on-time treatment. The elimination of other causes of GI bleeding and diarrhea, in addition to the two other factors mentioned above, would increase the survival rate of patients greatly.

Severe combined immunodeficiency is a true pediatric emergency; children with SCID were the first patients with immunodeficiencies to be successfully transplanted with unrelated and T-cell-depleted, haploidentical bone marrow. The pattern of inheritance of SCID is X-linked and autosomal recessive (ADA def, Jak3, RAG1, RAG2, IL 7Rα). In this case report, we describe a one-year-old boy with B+T- SCID who received unrelated cord blood transplantation from the Cord Blood Bank in Germany with a 4/6 HLA antigen match. The conditioning regimen was 1mg/kg/day Busulfan and 10mg/kg/day Cyclophosphamide. Both of them were given for two days. GVHD prophylaxis was performed with Cyclosporine A and Methotroxate.Stage III skin GVHD appeared on day 7 and gastric GVHD with a 250-300cc volume appeared on day 8. On day 14, CVP, CRP, LDH and SGOT increased, blood pressure decreased and arrhythmia with T change, AV block, RBBB and bradycardia appeared. With the conclusion of Myocarditis, the patient was treated with diuretics and limitation of liquid intake, Dexamethazone, Dopamine and IVIG. The heart condition was improved gradually. During hospitalization, there was no decrease in platelet count and radiated PRBCS transfusion was performed twice. The patient was discharged on day 60. Donor cell chimerism of 60% was detected with STR-PCR, which was followed up regularly and tapered the immunosuppressive therapy.Unrelated cord blood is a stem cell source in SCID patients and it is a curative treatment in patients without appropriate donors.