Impact Of Hematopoietic Stem Cell Transplantation Research Articles

Short-Term Impact of Hematopoietic Stem Cell Transplantation in Leukemia Patients on Bone Bio Markers, Electrolytes and Blood Profile

Hematopoietic stem cell transplantation (HSCT) or Bone Marrow Transplantation (BMT) has significantly improved the survival rates of patients suffering from hematological malignancies. However, the cure can only be achieved at the price of morbidity and long-term complications such as bone diseases leading to fractures and osteopenia. Several studies have reported the impact of organ transplants on bone metabolism, electrolytes and blood profile. This prospective observational clinical study aims at elucidating the effects of HSCT on bone metabolism, electrolytes and blood profile in leukemia patients. Sixty patients were included in this study. The current study aimed to evaluate the short-term (30 days) impact of HSCT on bone biomarkers [osteoprotegerin (OPG) and alkaline phosphatase], electrolytes (calcium, sodium, potassium, and magnesium), and blood profile [hemoglobin, absolute neutrophil count (ANC), platelet, and total leucocyte count (TLC)] in leukemia patients undergoing HSCT from their record files before HSCT (TP1) and after 30 days of HSCT (TP2). Further, the correlation among various parameters at TP2 was assessed using Spearman correlation analysis. At TP2, the level of OPG, alkaline phosphatase, calcium, magnesium and TLC increased significantly compared to TP1. However, no significant change was observed in other parameters at TP2 compared to TP1. A statistically significant positive correlation of TLC with hemoglobin and sodium; and magnesium with alkaline phosphatase was observed. Furthermore, a significant negative correlation between hemoglobin and calcium was observed. Even though there was a statistically significant increase in the level of OPG, alkaline phosphatase, calcium, magnesium and hemoglobin after 30 days of HSCT, the level of bone biomarkers, electrolytes and blood profile were in the normal physiological range. However, additional studies are required to get a detailed understanding of the changes in parameters after HSCT.

5606726 IMPACT OF ALLOGENEIC STEM CELL TRANSPLANTATION ON PHYSICAL, MENTAL, AND SOCIAL HEALTH OF ADULT SICKLE CELL DISEASE PATIENTS: A MIXED-METHODS STUDY

Background: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and recurrent painful vaso-occlusive crises, resulting in considerable physical and psychosocial disease burden and early mortality. In recent years, the application of allogeneic hematopoietic stem cell transplantation (HSCT) as a curative treatment for adult SCD patients has increased. As a result, a deeper understanding of the complex relationship between physical, mental, and social health before and after curation is needed. Aim: To explore the experiences and perspectives of adult SCD patients on the impact of HSCT on their physical, mental, and social health. Methods: A mixed methods study design, consisting of a semi-structured interview and completion of 9 Patient Reported Outcomes Measurement Information System (PROMIS®) item banks per participant was used. Adult SCD patients who underwent HSCT ≥ 1 year ago at the Amsterdam University Medical Center were eligible to take part in this study. Interviews were recorded, transcribed verbatim, and thematically analyzed using MAXQDA® software. Standardized T-scores of PROMIS® measures were evaluated and compared to reference scores of the Dutch general population. Results: Ten SCD patients with a median age of 29,5 years (range 19-49) were included in the study and interviewed between October 2021 and May 2022. Median time since HSCT was 2.7 years (range 1 - 3.5). All patients had successful engraftment. Relevant themes were (1) pain/living pain free, (2) physical wellbeing, (3) mental wellbeing, (4) perspective/outlook, (5) education and work, (6) family and friends and (7) activities and participation. Living pain free and the emergence of a future perspective were major improvements for most participants which resonated strongly in their daily lives. Nevertheless, emotional struggles with processing the impact of having had SCD on the one hand, while adjusting to the novel circumstances on the other hand, were common among participants. Before and after HSCT, participants experienced a lack of psychological help. Two patients with ongoing pain from avascular bone necrosis had mixed feelings about the success of the transplant. These two patients scored within the mild, moderate, or severe symptom category on ≥ 7 of 9 PROMIS® item banks. While mean PROMIS® T-scores of all participants fell within the reference values of the general population (Figure 1), a large variation between patients was observed which matched with our findings from the qualitative data. Conclusions: Adult SCD patients experience significant improvements in many aspects of their physical, mental, and social health after cure by HSCT. Yet, they are confronted with a new and often unfamiliar reality, which carries different challenges. Pain as a result of irreversible complications of SCD continues to have a negative impact on quality of life after HSCT. Clinicians should acknowledge these challenges and aim at creating realistic expectations in future transplant candidates. Moreover, patients expressed a need for tailored psychological care, which should be offered before and after HSCT.

Fertility preservation for pediatric patients with hemoglobinopathies: Multidisciplinary counseling needed to optimize outcomes.

Hemoglobinopathies are autosomal recessive disorders that occur when genetic mutations negatively impact the function of hemoglobin. Common hemoglobinopathies that are clinically significant include sickle cell disease, alpha thalassemia, and beta thalassemia. Advancements in disease-modifying and curative treatments for the common hemoglobinopathies over the past thirty years have led to improvements in patient quality of life and longevity for those who are affected. However, the diseases, their treatments and cures pose infertility risks, making fertility preservation counseling and treatment an important part of the contemporary comprehensive patient care. Sickle cell disease negatively impacts both male and female infertility, primarily by testicular failure and decreased ovarian reserve, respectively. Fertility in both males and females with beta thalassemia major are negatively impacted by iron deposition due to chronic blood transfusions. Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for SCD and transfusion dependent beta thalassemia. Many of the conditioning regimens for HSCT contain chemotherapeutic agents with known gonadotoxicity and whole-body radiation. Although most clinical studies on toxicity and impact of HSCT on long-term health do not evaluate fertility, gonadal failure is common. Male fertility preservation modalities that exist prior to gonadotoxic treatment include sperm banking for pubertal males and testicular cryopreservation for pre-pubertal boys. For female patients, fertility preservation options include oocyte cryopreservation and ovarian tissue cryopreservation. Oocyte cryopreservation requires controlled ovarian hyperstimulation (COH) with ten to fourteen days of intensive monitoring and medication administration. This is feasible once the patient has undergone menarche. Follicular growth is monitored via transvaginal or transabdominal ultrasound, and hormone levels are monitored through frequent blood work. Oocytes are then harvested via a minimally invasive approach under anesthesia. Complications of COH are more common in patients with hemoglobinopathies. Ovarian hyperstimulation syndrome creates a greater risk to patients with underlying vascular, pulmonary, and renal injury, as they may be less able to tolerate fluids shifts. Thus, it is critical to monitor patients undergoing COH closely with close collaboration between the hematology team and the reproductive endocrinology team. Counseling patients and families about future fertility must take into consideration the patient's disease, treatment history, and planned treatment, acknowledging current knowledge gaps.

Impact of TKI combination therapy and MRD negativity on outcomes in Philadelphia chromosome-positive ALL: A retrospective, single-center experience.

e19052 Background: Presence of the Philadelphia chromosome (Ph+) in newly diagnosed B-cell acute lymphoblastic leukemia (ALL) conveys high-risk disease and a poor prognosis. Hematopoietic stem cell transplant (HSCT) following induction and achievement of remission remains the standard of care. In the era of TKIs targeting BCR-ABL1 in addition to newer combination strategies, the impact of HSCT in the first complete remission (CR) remains unclear, particularly in the context of measurable residual disease (MRD) negativity. We present the outcomes of Ph+ B-ALL patients with and without HSCT, stratified with respect to MRD negativity. Methods: We identified 32 patients with Ph+ B-cell ALL from January 2015 to January 2021 at our institution who were treated with TKIs and received HSCT with evaluable MRD prior to transplant. Baseline patient demographics were obtained, including labs, performance status at diagnosis, comorbidities, molecular profiling by NGS, doses of induction, toxicities, response, MRD analysis by PCR, HCT-CI scores, and HSCT outcomes. The event for calculating the overall survival (OS) was the date of death. Patients were otherwise censored at the date of last contact. Results: Of the 25 patients who underwent HSCT, the median age was 46 years and 48.0% were male. TKIs in combination with high-intensity regimens were given in 88.0% of patients at induction. There were no deaths within 60 days following induction. Twenty (80.0%) patients achieved CR or CRi, and of those, 56% were MRD-negative by the time of HSCT. At a median follow-up time of 4.74 years, the OS of patients that achieved CR following induction and HSCT was not reached, and there were no significant differences between the two groups (p = .1326). We then compared the 14 MRD-negative patients undergoing HSCT to 7 MRD-negative patients who did not undergo transplant aged ≤65 years with ECOG ≤2. There was no difference in age (p = .5353), ECOG score (p = .6364), or Charlson Comorbidity Index score (p = .7018) between the two groups. The median OS in the MRD-negative HSCT group was not reached and the median OS in the MRD-negative non-HSCT was 5.45 years (p = .0210). Conclusions: In the era of combination chemotherapy with TKIs, MRD positivity at the time of allogenic HSCT does not appear to impact survival at 5 years in this small retrospective cohort. Post-transplant TKI maintenance may abrogate MRD implications at the time of HSCT. Our findings demonstrate that Ph+ ALL patients benefit from HSCT when candidates, regardless of MRD status, as those undergoing HSCT demonstrated a statistically superior survival. HSCT appears to remain the standard of care despite newer combination strategies and MRD-driven treatment.

Hematopoietic Stem Cell Transplantation Stabilizes Cerebral Vasculopathy in High-Risk Pediatric Sickle Cell Disease Patients: Evidence From a Referral Transplant Center.

BackgroundSevere sickle cell disease (SCD) can present with different vaso-occlusive manifestations with cerebral vasculopathy (CV) as one of the most serious complications. Hematopoietic stem cell transplant (HSCT) is the ultimate therapy for this complication. The aim of this study was to assess the outcome and impact of HSCT on severe SCD patients with CV complications.MethodsTwenty-five consecutive transplants-naive pediatric SCD patients with CV complications underwent HSCT at our institution between 1993 and 2015, using bone marrow as stem cells source from fully match related donors were included. Neurologic evaluation was done both clinically and radiologically before transplantation and regularly following the HSCT.ResultsWith a median follow-up of 52.2 ± 5.8 months, the cumulative probability of overall survival (OS) at 3 years was 92.0% and event-free survival (EFS) was 88%. Significant neurologic improvements were observed in most of the patients clinically. Different neurologic complications were assessed. The neurologic manifestations before and after HSCT were hemiparesis (11, 1), seizures (13, 8), focal neurologic deficit (4, 2), loss of conscious (2, 1) headache (6, 1), and psychological symptoms (5, 2). Post-HSCT radiological imaging was done in 15 patients, which showed stabilization of CV among all.ConclusionsAllogeneic HSCT in patients with severe SCD presenting with CV complications including moyamoya vasculopathy showed favorable outcome with significant clinical neurologic improvement and stabilization of the disease. None of the patients with severe vasculopathy underwent neurological vascular by-pass surgery prior to HSCT.

Nonmyeloablative Transplant for Sickle Cell Disease Does Not Lead to Kidney Dysfunction Post-HSCT

Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with sickle cell disease (SCD). Though HSCT can reverse the SCD phenotype, both acute kidney injury (AKI) and chronic kidney disease (CKD) have been associated with HSCT. SCD alters renal function thus the impact of HSCT on renal function in SCD patients is a critical area of exploration. Here, we report the effect of HSCT on renal function in people with SCD.This study analyzes data from 195 patients who received HLA-matched sibling or haploidentical HSCT for SCD at Imperial College London (ICL), National Institutes of Health (NIH), and University of Illinois Chicago (UIC). The former is a pediatric cohort and all sites employed a nonmyeloablative conditioning. Patients' renal function was assessed at baseline and annually thereafter for up to 3-years.We examined the prevalence of CKD before and after HSCT, estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) trends after HSCT, and the incidence of AKI within 100 days of HSCT. We defined and staged AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria; we calculated eGFR with the CKD- epidemiology collaboration (CKD-EPI) equation for adults and Bedside Schwartz for children.The median eGFR declined annually but remained within the normal range throughout the follow-up period: the baseline median eGFR was 138 ml/min/1.73m 2 and declined by 7 in the first year of follow-up and by additional decreases of 5 and 3.6 ml/min/1.73m 2 in subsequent years (p-values of 0.07, 0.0002, and 0.0002 for years 1, 2, and 3 for comparison to baseline from regression model of eGFR). No differences in eGFR were seen for covariates in the model: haploidentical vs. matched sibling, engraftment status, gender, or site. The downward eGFR trend may represent an improvement in renal function toward normal as hyperfiltration (eGFR ≥150 ml/min/1.73m 2) was present in 28% of patients at baseline and steadily declined to 7% by 3 years post-HSCT. There was a corresponding increase in patients with normal eGFR (60-149 ml/min/1.73m 2) from 59% at baseline to 88% at 3 years post-HSCT.Among the ICL and NIH cohorts (UIC excluded due to use of a different AKI determination strategy), 58% of patients developed AKI in the early post-HSCT period. 67% of AKI cases were mild, stage 1; 25% were moderate, stage 2; and 8% were severe, stage 3 AKI.This study demonstrates that HSCT in patients with SCD is associated with a transient increase in UACR but not associated with a significant increase in CKD prevalence by 3-years post-HSCT. The stability of UACR compared to baseline by the 3-year time point suggests that even more mild renal damage may stabilize after HSCT. While there is a substantial decline in eGFR from baseline to each annual follow-up, the proportion of patients whose eGFR was in the normal range increased as the prevalence of hyperfiltration decreased. Finally, while AKI occurred in more than half the patients in our cohort, the preponderance developed only mild AKI. Therefore, our data indicate that nonmyeloablative HSCT for SCD does not lead to significant kidney dysfunction post-HSCT. DisclosuresSaraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Diamantidis: United Health Group: Consultancy.

Post-Traumatic Stress Symptoms in Hematopoietic Stem Cell Transplant Recipients

Hematopoietic stem cell transplantation (HCT) is an intensive and potentially curative therapy for patients with hematologic malignancies. Patients admitted for HCT experience a prolonged, isolating hospitalization and endure substantial physical and psychological symptoms. However, there is a paucity of research on the impact of HCT on post-traumatic stress disorder (PTSD) symptoms in transplant recipients. This secondary analysis of 250 patients who underwent autologous and allogeneic HCT examined PTSD using the PTSD Checklist-Civilian measured at 6 months after HCT. We used the Functional Assessment of Cancer Therapy-Bone Marrow Transplant, and the Hospital Anxiety and Depression Scale to assess quality of life (QOL) and depression and anxiety symptoms at the time of admission for HCT, week 2 during hospitalization, and 6 months after HCT. We used multivariate regression models to assess factors associated with PTSD symptoms. Given collinearity between QOL, depression, and anxiety symptoms, we modeled these separately. The rate of clinically significant PTSD symptoms at 6 months after HCT was 18.9% (39/206). Participants with clinically significant PTSD symptoms experienced hypervigilance (92.3%), avoidance (92.3%), and intrusion (76.9%) symptoms. Among patients without clinically significant PTSD symptoms, 24.5% had clinically significant hypervigilance symptoms and 13.7% had clinically significant avoidance symptoms. Lower QOL at time of HCT admission (B=-0.04, P=.004) and being single (B=-3.35, P=.027) were associated with higher PTSD symptoms at 6 months after HCT. Higher anxiety at time of HCT admission (B=1.34, P <.001), change in anxiety during HCT hospitalization (B=0.59, P =.006), and being single (B=-3.50, P=.017) were associated with higher PTSD symptoms at 6 months. In a separate model using depression, younger age (B=-0.13, P=.017), being single (B=-3.58, P=.018), and higher baseline depression symptoms were also associated with higher PTSD symptoms at 6 months (B=0.97, P < .001). Approximately one fifth of patients undergoing HCT experience clinically significant PTSD symptoms at 6 months after transplantation. The prevalence of hypervigilance and avoidance symptoms are notable even among patients who do not have clinically significant PTSD symptoms. Interventions to prevent and treat PTSD symptoms in HCT recipients are clearly warranted.

Ovarian function after allogeneic hematopoietic stem cell transplantation in children and young adults given 8‐Gy total body irradiation‐based reduced‐toxicity myeloablative conditioning

The spectrum of late sequelae after hematopoietic stem cell transplantation (HSCT) includes infertility, which is the most frequent complication. Some reports suggested that ovarian function may be better preserved in females undergoing HSCT with reduced-intensity conditioning (RIC) than with conventional myeloablative conditioning (MAC). However, the impact of HSCT after 8-Gy TBI-based reduced-toxicity MAC (RTMAC), whose efficacy is between those of conventional MAC and RIC, on ovarian function remains unclear. A single-center retrospective analysis of data derived from patient information for all the children who underwent transplantation at the Shinshu University Hospital was carried out. Patients who underwent 8-Gy total body irradiation (TBI)-based RTMAC before HSCT were analyzed. A total of 36% (five of 14) of the patients developed primary ovarian insufficiency (POI) during the observation period, but serum follicle-stimulating hormone levels reduced to normal range with spontaneous menstruation in two, implying the reversal of POI. Furthermore, only one (10%) of the 10 prepubertal patients (71%; 10/14) at the time of HSCT suffered from POI at the last observation, but all three post-pubertal patients developed POI (100%), and two (67%) continued to suffer from POI at the last observation. Taken together, 8-Gy TBI-based RTMAC before HSCT may decrease the possibility of POI compared with conventional MAC, especially in prepubertal patients. A longer follow-up will be required to ascertain whether a normal pregnancy and delivery can occur in such patients.

Experiences and Decision Making in Hematopoietic Stem Cell Transplant in Sickle Cell Disease: Patients' and Caregivers' Perspectives

Sickle cell disease (SCD) is one of the most commonly inherited hemoglobin disorders that has a significant impact on quality of life, increased childhood morbidity, and premature mortality. Currently, hematopoietic stem cell transplant (HSCT) is the only treatment with a curative intent. The objective of this study was to determine patients' and caregivers' knowledge of HSCT, the factors influencing the decision to pursue HSCT, their experiences, and the impact of a successful HSCT on their daily living. At Children's Healthcare of Atlanta, we conducted a qualitative study using a semistructured interview guide of patient-caregiver dyads and 2 focus-group sessions of adult long-term survivors of HSCT to elicit key factors in decision making, their experiences with HSCT, and the impact of HSCT. Interviews and focus-group sessions were recorded and transcribed verbatim. Transcripts were coded and analyzed for emerging themes using NVivo 10.0. We enrolled 11 patient-caregiver dyads (n = 6, female patients; n = 10, mothers) in the qualitative interviews and 2 focus groups with 5 (n = 2, females) and 7 (n = 3, females) participants in each group, respectively. Our analysis revealed 3 prominent themes: (1) factors and concerns influencing HSCT decision making; (2) HSCT experiences; and (3) impact of HSCT on daily life. Participants reported that progression of disease-related complications and availability of a matched donor strongly influenced the decision to pursue HSCT. Although patients and caregivers had to deal with the arduous process of HSCT and transplant-related morbidities, participants were satisfied with their decision and expressed no decisional regrets. Decision making for HSCT for patients with SCD is a complex process. Understanding the key influential factors in decision making and the impact HSCT has on these patients and their families will generate crucial insights that can guide the care of future patients and research studies.

Successes and Challenges of Pediatric AML: A Report on Survival, Salvage Therapy and Causes of Deaths in the AML-BFM Study Group from 1987 -2012

Background:Over the past 30 years, prospective randomized trials led to a markedly increased overall survival (OS) for pediatric patients with acute myeloid leukemia (AML). While hematopoietic stem cell transplantation (HSCT) was previously recommended to all patients with available matched sibling donor in first remission, recent protocols mainly restricted allogeneic HSCT to patients with very high relapse risk, refractory disease or after relapse. At the same time, the first-line treatment was heavily intensified, while supportive care was greatly improved. Also recent studies for relapsed patients demonstrated an improved, but still poor outcome (5yr-pOS: 24-38%). Thus, the factors that mainly contributed to the markedly increased OS in pediatric AML remain largely unknown. Here we present a retrospective analysis, which we performed to reveal those factors, but also to identify the obstacles that may hamper further improvement.Patients and Methods:From 1/1987 to 12/2012, a total of 1940 patients with de novo AML were enrolled in four consecutive trials of the AML-Berlin/Frankfurt/Muenster study group (AML-BFM-87, -93, -98, -04 and the following registry). Median follow-up was 10 years. Five year estimates of EFS and OS (pEFS, pOS), cumulative incidences (CI) of early death (ED), death in nonresponse (NR), death in complete remission (CR) or deaths of patients with one or more relapses were analyzed retrospectively over time in 3-year and 9-year periods and also according to study periods.Results:In this large population of 1940 patients with, we sought to systematically decipher the causes of death, incidences and survival after relapse or NR and the impact of HSCT in pediatric AML. As previously shown, the 5yr-pOS markedly increased from 52±4% (1987-1989) to 72±5% (2011-2012) (p<0.0001), but improvement of 5yr-pEFS was unsteady from 43±3% to 55±5%. This implies that factors after the first event are responsible for the better survival. Accordingly, the OS of patients with NR (n=48, OS 13±5% [AML-BFM 87], vs. n=65, OS 41±6% [AML-BFM 04]; p<0.001) and relapse (n=97, OS 19±4% [AML-BFM 87] vs. n=204, OS 42±4%, [AML-BFM 04]; p<0.001) improved remarkably (Figure 1). Treatment intensification resulted generally in less disease-related deaths in most subgroups, but in turn was associated with higher treatment-and procedure-related mortality over the last 25 years. Incidences of ED significantly decreased (p=0.002). More specifically, disease-related causes within this group decreased, whereas treatment-related deaths did not change (Figure 2). Patients with NR also showed less disease-related deaths in recent compared to the earlier cohorts (p=0.001), and no change in treatment-related lethality (p=0.43). In the recent cohort, we observed a trend of fewer deaths in CR. Treatment-related deaths decreased significantly (p=0.02). CI of death after relapse showed a remarkable decrease over time. This is mostly affecting disease-related deaths (p<0.011), while deaths due to HSCT increased (p=0.008). Deaths in patients with more than one relapse did not change, and the only significant change within this subgroup is a higher incidence of HSCT-related deaths. The increase of HSCT in first CR and after NR/relapse from 25% 1987 - 1995 to about 40% after 1995 translates into a higher incidence of procedure-treatment related deaths. Nevertheless OS of patients with HSCT after NR/relapse increased significantly (OS 35±5% [1987-1995], 37±4 [1996-2004] and 51±4% [2005-2012] (p=0.001)). The comparison within study periods showed no trend for a better pEFS and pOS in the second half of a study compared to the first so an improvement due to general measures like better supportive care cannot be proven. In a Cox regression analysis of OS there was a significant trend for better OS over the study periods (HR 0.88, 95% confidence interval 0.72-0.82) but not for better OS in the second half (HR 0.95, 0.82-1.09).Conclusion:In conclusion, efficacy of salvage therapy and better therapy strategy is one of the main reasons for improved outcome in pediatric AML within the last 3 decades. However, stable and in some subgroups decreased treatment-related mortality reflects better supportive care with respect to intensified therapy. Of note, procedure-related mortality increased, but nevertheless survival after HSCT improved. [Display omitted] [Display omitted] DisclosuresRasche:Jazz Pharma: Other: Travel accomodation. Reinhardt:Celgene: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Other: Travel Accomodation; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees.

Predictors of health-related quality of life over time among pediatric hematopoietic stem cell transplant recipients.

Advances in hematopoietic stem cell transplantation (HSCT) have contributed to increased survival for pediatric patients. However, there are inconsistent findings regarding the impact of HSCT on health-related quality of life (HRQOL) outcomes for children. This study aimed to establish trajectories of HRQOL following HSCT and identify predictors of the HRQOL course. Ninety caregivers of a child who received HSCT (mean age = 6.42 years) for various oncologic, immunologic, and metabolic conditions completed questionnaires regarding family psychosocial functioning and child HRQOL at the time of discharge from HSCT and follow-up HRQOL at four additional time points. There was a significant change in overall HRQOL in 3 months postdischarge, with the greatest improvement in physical functioning. Caregiver stress and social support, and child psychosocial problems predicted changes in HRQOL over time. These results point to potentially modifiable factors that are related to the course of HRQOL following HSCT, and interventions aimed at these factors should be implemented.

Relapsed Follicular Lymphoma Treatment - with or without Hematopoietic Stem Cell Transplant?

BACKGROUNDThe best treatment strategy in patients with relapsed Follicular Lymphoma (FL) remains controversial. The incorporation of rituximab (R) in the 1st line chemotherapy (CT) regimen and in treatment relapse resulted in better progression-free survival (PFS) but the benefit in overall survival (OS) was observed in only one trial (Hiddemann W. et al, Blood 2006). Hematopoietic stem cell transplant (HSCT) is the only treatment potentially curative, although the ideal time for its implementation remains undefined. AIMEvaluation of the best treatment strategy and the impact of HSCT in PFS and OS in patients with relapsed FL. METHODSRetrospective study including 85 patients with relapsed FL followed at a cancer care center between 2000-2012. Selection criteria: treatment naïve patients with the diagnosis of FL; absence of histological transformation at diagnosis and/or during the 1st line treatment. Survival analysis using the Kaplan-Meier method. Type of response defined according to NCCN criteria. RESULTSMedian follow-up of 64 months [4-158]. Disease progression after the 1st line CT was documented in 85 patients (median age 51 years [28-78], 42.4% male). 64 of the 85 patients had an Ann Arbor stage III-IV, of which 85.9% with follicular pattern, 95.3% grade 1/2 and 43.8% FLIPI ≥ 3. All patients underwent one or more CT regimens containing R, except in one case. In this study, 27.1% (n = 23) patients with age ≤ 60 years were submitted to HSCT (52.2% allogeneic HSCT from a related donor versus 47.8% autologous HSCT), almost all with ≥ 2 prior lines of CT (95.6%, n = 22). 78.3% (n = 18) had a CR or PR> 75% at the time of HSCT, and one death related to graft versus host disease was registered. Patients undergoing HSCT had a better PFS than those not transplanted (p = 0.022). A significant improvement in OS was observed in the HSCT subgroup (p = 0.007), especially in those with stage III-IV (p = 0.006). The type of HSCT had no impact on PFS and OS (p> 0.05), perhaps due to the small number of patients and short follow-up. By univariate Cox regression analysis, the number of regimens of CT before HSCT and the histological grade were independent predictors of PFS (p <0.05). The age and the histological grade were independent predictors of OS (p <0.05). CONCLUSIONIn this study, HSCT improved PFS and also OS in patients with relapsed FL, especially in patients receiving less than 3 CT regimen, highlighting the importance of completing the HSCT earlier, during the disease’s chemosensitive phase. Our data suggest the curative potential of HSCT in these patients, due to the GVL effect in allogeneic HSCT and/or intensive high-dose CT in autologous HSCT. More studies are needed to validate these observations. DisclosuresNo relevant conflicts of interest to declare.

Excellent outcomes of children with CML treated with imatinib mesylate compared to that in pre-imatinib era

Allogeneic hematopoietic stem cell transplantation (HSCT) and tyrosine kinase inhibitor have revolutionized the treatment of patients with chronic myeloid leukemia (CML). In this study, the clinical impact of HSCT and imatinib mesylate (IM) was retrospectively analyzed in 28 children with CML treated in our institutes from 1984 to 2008. Twelve patients were given oral IM. At 36months after initiation of IM therapy, the complete cytogenetic response rate was 90.9%, and the major molecular response rate was 36.4%. Sixteen children received allogeneic HSCT without administration of IM. The stage of disease at transplantation was: first chronic phase (n=10), second chronic phase (n=2), accelerated phase (n=2), and blastic crisis (n=2). The progression rate was significantly lower in patients treated with IM than in those treated without IM (0 vs. 28.6%, p=0.006). In summary, the survival outcomes of pediatric patients with CML were dramatically improved by treatment with IM compared to HSCT.

Hematopoietic Stem Cell Transplant (HSCT) as Primary Treatment for T-Cell Lymphobastic Lymphoma (T-LBL) : An Intention to Treat Analysis.

The role of HSCT for T-LBL is not well defined. Most series are subject to referral bias and do not address the true impact of HSCT, especially as primary treatment. Since 1987 all patients in British Columbia with T-LBL have been considered eligible for HSCT as part of primary treatment. Between 6/87–12/03, 27 patients were diagnosed with T-LBL. Patients with &gt; 25% involvement of the bone marrow were excluded. Characteristics: Age range 18–56 y (median 26); M:F 19:8; Ann Arbor stage I-II 6; III-IV 21; bone marrow involved 7/27; peripheral blood involved 2/27; CNS involved 1/27; LDH elevated 15/25; mediastinal mass 23/27. Initial treatment: All received an anthracycline-containing regimen similar to CHOP. All achieved at least a partial remission. HSCT: 23/27 (85%) proceeded to HSCT in first response. Source of stem cells: 4, related donor (2 marrow, 2 peripheral blood); 19, autologous (15, mafosphamide purged marrow; 1, 4-hydroperoxy-cyclophosphamide purged marrow; 1, unpurged marrow; 1, unpurged peripheral blood; 1, combined unpurged marrow and peripheral blood). Conditioning was cyclophosphamide (150 mg/kg) and TBI (750–1200 cGy) +/− etoposide 1.8 g/m2 in 22 of 23 patients. CNS prophylaxis with intrathecal methotrexate and cytarabine was planned for all patients. All 23 had maintained chemosensitivity at time of HSCT. Time from diagnosis to HSCT was 1.3–6.4 months (median 2.2). Reasons for not proceeding to HSCT 2 refused; 1 decided to wait until relapse; 1 did not have adequate organ function. Median follow-up of living patients was 33 months (range 4–142 months). Results: Overall survival (OS) and event free survival (EFS) at 3 years for all patients were 79% (95% CI 61–97%) and 75% (95% CI 57–93%); patients who underwent HSCT 85% (95% CI 70–100%) and 81% (95% CI 64–98%). 4 patients relapsed post HSCT at 2.2, 10.8, 11.7 and 40.4 months post HSCT. Sites of relapse: 2, mediastinum; 1, bone marrow; 1, mediastinum and bone marrow. One patient who received HSCT died of a treatment related complication (interstitial pneumonitis). Significant factors for improved survival post HSCT (univariate): Absence of bone marrow involvement [EFS at 3 years 92% vs 57% (p=0.026)]. Non-significant factors: normal LDH, stage I/II at diagnosis, age &lt; 30 yrs. Conclusions: Patients with T-cell lymphoblastic lymphoma treated with a CHOP-like regimen achieve adequate control of disease to proceed to HSCT. HSCT as primary treatment results in excellent long-term disease free survival with acceptably low treatment related mortality. Bone marrow involvement at diagnosis, even though &lt; 25%, predicts for a worse outcome.