Favorable Outcome and Quality of Life in Patients Surviving 5 or More Years After Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3312-3312
Author(s):  
Robert Quan Le ◽  
Margaret Bevans ◽  
Bipin N. Savani ◽  
Sandra Mitchell ◽  
Kate Stringaris ◽  
...  

Abstract Abstract 3312 Poster Board III-200 Allogeneic hematopoietic stem cell transplantation (SCT) is a curative treatment for some hematological malignancies. The ultimate measure of success of allogeneic SCT for hematological malignancies is its ability to eradicate malignant disease and restore a good quality of life (QOL) in long-term survivors. As numbers of survivors continue to increase, studies systematically examining outcomes in this group of survivors are needed. We studied the clinical and QOL outcomes in a large cohort of patients with hematological malignancies surviving 5 or more years after allogeneic SCT from a single institution. In 2005 we initiated a long term follow up protocol to further study complications in survivors after allogeneic SCT. Patients were enrolled at the third annual visit after transplantation. Annual follow-up visit includes comprehensive clinical evaluation and detailed assessment of QOL, symptom distress, physical and mental health. Measures for QOL included the Functional Assessment of Cancer Therapy-General (FACT-G), the Physical and Mental Component Summary scales (PCS, MCS) of the Medical Outcomes Short-Form 36 (SF-36), and the Rotterdam Symptom Checklist (RSCL). Two hundred sixty two patients with hematological disorder received a SCT from an HLA identical sibling since 1993. One hundred and twenty one patients (46 %) survived 3 or more years and were eligible for participation in the long-term evaluation protocol. Ninety two (35%) survived beyond 5 years from SCT (median follow-up 9.4 years, range 5.1-15.3) and were included in this analysis. Median age at transplantation was 35 years (range 10 - 56). Twenty-two (24%) received a bone marrow transplant, and 70 (76%) received a peripheral blood SCT. We examined chronic graft-versus-host-disease (cGVHD), disease relapse, survival and QOL. Seventeen (18%) of 92 survivors had active cGVHD (limited 9, extensive 8) and were receiving prolonged immunosuppressive treatment 5 years following allogeneic SCT. Four relapsed with leukemia, at a median of 8.5 years (range 6.2 -14.0) post SCT. Four (4.3%) died between 7.4 -13.4 years post SCT (1 relapse, 1 lung cancer, 1 pneumonia, 1 brain hemorrhage). Sixty (65%) completed QOL measures. Most survivors beyond 5 years had an excellent performance status with no difference in the PCS (p =0.89) and MCS (p =0.15) scores and higher FACT-G scores compared with population norms (p =0.02). Although the overall distress for physical and psychological symptoms was low, higher levels of symptom distress were associated with impairments in QOL. In eleven survivors with cGVHD, there was no statistical difference across QOL outcomes although the difference was meaningfully lower (≥5 points). In conclusion, five or more years after SCT for hematological malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent QOL. However patients with leukemia appear to have a persistent but low chance of disease recurrence. Although cGVHD persists in about 20% of patients it did not appear to affect the excellent QOL that most of our patients experience. The association between cGVHD severity and specific cGVHD manifestations and QOL outcomes requires further study. Disclosures No relevant conflicts of interest to declare.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3061-3061
Author(s):  
Maria Teresa Lupo-Stanghellini ◽  
Giacomo Oliveira ◽  
Raffaella Greco ◽  
Luca Vago ◽  
Attilio Bondanza ◽  
...  

Abstract Abstract 3061 Background and methods. Suicide gene therapy (SGT) applied to allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been one of the first clinical applications of gene therapy. In allo-HSCT the antileukemic potential mediated by alloreactive lymphocytes towards patient-specific antigens, such as minor and major histocompatibility antigens, is counterbalanced by the Graft-versus-Host-Disease (GvHD). The risk of GvHD increases with the level of HLA disparity between host and donor, and leads to impaired quality of life and reduced survival, particularly in patients (pts) transplanted from HLA-mismatched donors. In this contest SGT has been applied to modulate alloreactivity, by inserting the HSV-tk gene in donor lymphocytes. This suicide gene/prodrug system requires cell cycle for optimal killing. In the context of allo-HSCT, this characteristic ensures a further level of specificity in GvHD control, by allowing to selectively kill highly proliferating alloreactive cells during GvHD, while sparing resting T cells. We assessed long-term safety in TK cells treated pts. Results. Overall 128 pts have been treated worldwide in 10 phase I-II clinical trials with donor lymphocytes expressing the HSV-tk suicide gene, with the purpose of enforcing the graft-versus-tumor (GvT) effect and/or promoting a functional post-transplant immune reconstitution (IR) while allowing control of GvHD. This approach proved highly feasible, safe and effective in promoting a dynamic and patient-specific modulation of alloreactivity. TK cells engrafted in the majority of pts and a clinical benefit, measured as improvement of hematopoietic chimerism, malignant regression and/or IR, was reported for 65 pts (51%). GvHD grade II-IV was observed in 28 pts (22%) and was always rapidly and completely controlled by the activation of suicide machinery. A selected population of 57 pts, treated at San Raffaele Institution, was studied in more detail for long-term analysis: 23 pts received cells to treat relapse occurring after an HLA-identical allo-HSCT (Ciceri F et al, Blood. 2007: 109; 4698–470) and 34 pts to improve IR after haploidentical HSCT (Bonini C et al, Blood. 2002; 100: 115a; Ciceri F, Bonini C et al, Lancet Oncology. 2009; 10: 489–500). No adverse event correlated to the gene transfer procedure was ever reported. Genetically modified cells engrafted in 90% of treated pts and could be detected in vivo, at low frequencies for up to 14 years (y). In the HLA-identical setting 11 pts obtained clinical response of the malignant disease and 3/11 are alive with a median follow-up of 15y. Two pts are in complete remission (CR), while one pt affected by chronic myelomonocytic leukemia relapsed 15y post transplant. This pt was subsequently treated with a second transplant from an unrelated match donor and is now in CR 1 year after transplant. In the haploidentical setting, 25 pts/34 reached the target of IR and 9 are alive and in CR with a median follow-up of 7y. Four out of 9 experienced GVHD in the early phase post IR, none presented signs, symptoms, complications related to GvHD and none needed pharmacological treatment in long-term. According to international guideline for long-term follow-up (Majhail NS et al, BBMT. 2012; 18: 348–371) all pts underwent regular screening and clinical evaluation. No major infections occurred in the late phase, no ocular, oral, respiratory, hepatic, renal, genitourinary, muscle-skeletal or neurological distress. Noteworthy 3 pts developed second cancer (2 skin cancer non-melanoma, 1 endometrial cancer), 2 pt hypothyroidism, 1 pt coronary artery disease and 3 pts metabolic syndrome. No evidence of psychosocial symptoms was reported. Immunity against the transgene was reported in pts who received TK cells late after an HLA-identical allo-SCT. The quality of IR at the time of TK cells administration was the most predictive variable. On the contrary, no immunity against HSV-tk was ever detected in pts who received TK cells after transplantation of haploidentical CD34-selected cells, indicating that the infusion of TK cells to highly immunosuppressed pts is not limited by the development of transgene-specific immune responses. Conclusions. Long-term assessment confirmed the overall high benefit/risk ratio of the TK-cell approach in allo-HSCT. A phase III multicentric, randomized clinical trial sponsored by MolMed, is currently undergoing in the context of haploidentical HSCT. Disclosures: Bordignon: MolMed SpA: Employment. Bonini:MolMed S.p.A.: Consultancy.


Sign in / Sign up

Export Citation Format

Share Document