High International Prognostic Scoring System Research Articles

Immunosuppressive Treatment Is Associated with Durable Responses and a Survival Advantage in Younger Patients with int-1 Myelodysplastic Syndrome.

Immunosuppressive therapy (IST) can improve cytopenias in selected patients with myelodysplastic syndrome (MDS). Between 1998 and 2004, 129 patients with MDS [94 int-1, 13 int-2, 16 low and 6 high International Prognostic Scoring System (IPSS) stage] were given IST on investigational protocols: 116 received ATG 160mg/kg, 42 with additional cyclosporine (CsA); 13 received CsA alone for up to 6 months. Mean follow-up was 47 (range 0.7–120) months. Previously, we reported a score, using HLA-DR15 type, age and duration of red cell transfusion-dependence to segregate patients into high probability (HP), intermediate probability (IP), and low probability (LP) of hematological response to IST. Here we compare survival, response, and leukemic progression in HP and LP/IP NIH IST-treated patients and in non-IST controls enrolled in the International MDS Risk Analysis Workshop (IMRAW) (Blood 89:2079, 1997). Overall, 29% of NIH IST patients responded: HP patients (median ages for HP and the combined LP/IP] were 49 and 65 yr, respectively) were more likely to respond to IST than LP patients 38/55 (69%) vs 0/71 plus 0/3 IP; p<0.0001) (IP was included in LP group for analysis of survival), with better responses to ATG/CsA than with ATG alone (p=0.015). Neither abnormal cytogenetics nor bone marrow cellularity affected the response rate independent of IPSS int-1 or HP status. Seven of eight (87%) int-1 patients ≤ 60 with trisomy 8 as the sole abnormality and 16/34 with normal cytogenetics (47%) responded to one course of ATG; all 11 int-1 patients with 5q- were >60 years of age and none responded to IST. Marrow cellularity did not influence response to IST. Only two responders relapsed and required re-treatment with ATG; both responded to the second treatment. All but one patient with trisomy 8 increased the percentage of these cells in the marrow following therapy; the two responding monosomy 7 patients showed normal cytogenetics and FISH analysis following response to therapy. Age and IPSS stage were the major factors affecting survival in both treated and untreated patients. The actuarial survival of the 44 IST int-1 patients (median age 54) age ≤ 60 was superior to the untreated 87 int-1 IMRAW patients age ≤ 60 years (median age 48); the projected median survival was >16.4 years for the IST group and 5.2 years for the IMRAW group (p=0.0016), while there was no difference in survival between IST and IMRAW int-1 patients > 60 years of age (p=NS). Leukemic evolution was also decreased in the int-1 IST treated group ≤ 60 years of age compared to the comparable conservatively treated IMRAW group (projected time for 25% pts to develop AML was >16.4 years for IST patients vs 6.9 years for the IMRAW group) (p<0.001). These findings indicate that our IPSS int-1 patients ≤age 60 who received IST had improved survival compared to an untreated historical control group and that combined ATG/CsA gave superior responses compared to ATG alone.

Optimization of Transplant Regimens for Patients with Myelodysplastic Syndrome (MDS)

Myelodysplastic syndrome (MDS) is a hemopoietic stem cell disorder that is potentially curable by transplantation of normal hemopoietic stem cells. The optimum timing, however, and the best conditioning strategy have remained controversial. Both conventional and reduced-intensity/nonmyeloablative regimens have been used successfully. Among selected patients with less advanced/low-risk MDS (< 5% marrow myeloblasts), 3-year survivals of 65% to 75% are achievable with HLA-matched related and unrelated donors. Among patients with more advanced/ high-risk disease (> or = 5% marrow blasts; high International Prognostic Scoring System [IPSS] scores), the probability of post-transplant relapse ranges from 10% to 40%, and, as a result, relapse-free survival is inferior. In addition to disease stage, co-morbid conditions, pre-transplant chemotherapy, conditioning regimen, source of stem cells, and post-transplant immunosuppression affect transplant outcome. Reduced-intensity conditioning regimens are associated with a decrease in non-relapse mortality and allow for successful hemopoietic stem cell transplants even in patients 60-70 years of age. Graft-versus-host disease, both acute and chronic, and post-transplant relapse remain challenging problems.

A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome

AbstractBone marrow transplantation (BMT) can cure myelodysplastic syndrome (MDS), although transplantation carries significant risks of morbidity and mortality. Because the optimal timing of HLA-matched BMT for MDS is unknown, we constructed a Markov model to examine 3 transplantation strategies for newly diagnosed MDS: transplantation at diagnosis, transplantation at leukemic progression, and transplantation at an interval from diagnosis but prior to leukemic progression. Analyses using individual patient risk-assessment data from transplantation and nontransplantation registries were performed for all 4 International Prognostic Scoring System (IPSS) risk groups with adjustments for quality of life (QoL). For low and intermediate-1 IPSS groups, delayed transplantation maximized overall survival. Transplantation prior to leukemic transformation was associated with a greater number of life years than transplantation at the time of leukemic progression. In a cohort of patients under the age of 40 years, an even more marked survival advantage for delayed transplantation was noted. For intermediate-2 and high IPSS groups, transplantation at diagnosis maximized overall survival. No changes in the optimal transplantation strategies were noted when QoL adjustments were incorporated. For low- and intermediate-1-risk MDS, delayed BMT is associated with maximal life expectancy, whereas immediate transplantation for intermediate-2- and high-risk disease is associated with maximal life expectancy. (Blood. 2004;104:579-585)