Correlation of CD3 and CD34 cell dose with incidence of acute GVHD in myeloablative stem cell transplantation

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6553-6553
Author(s):  
A. Saad ◽  
N. Visweshwar ◽  
A. Sehbai ◽  
A. Cumpston ◽  
K. Watkins ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Stem Cell Transplant ◽  
T Test ◽  
P Value ◽  
Cell Transplant ◽  
Cell Product ◽  
Stem Cell Product

6553 Background: Allogeneic stem cell transplantation is used to treat different types of hematologic malignancies. The target stem cell dose typically is based on the recipient’s ideal body weight (IBW) with CD34 dose of 2.0–5.0 ×106/Kg. The dose of CD3 in the infusate is typically not taken into account in a stem cell product, except in T-depleted transplantation. The dose of T-cells in peripheral blood stem cell collections has been found to be at least 10-fold more than that in a bone marrow harvest product. Combined CD4+ and CD25+ cells infused have been directly correlated with increased incidence of GVHD. Methods: This is a retrospective study reporting the correlation of the CD34 and CD3 doses of stem cell transplant with incidence of acute GVHD in 67 consecutive patients who were treated between 2003 and 2005. All patients were followed up for at least 100 days following the stem cell transplant. Results: Among the 67 patients, 35 patients developed acute GVHD, while 32 patients had no evidence of acute GVHD. The CD3 and CD34 doses did not correlate. The correlation coefficient was 0.14 (P value: 0.27). Using t-test, there was NO statistical difference between the mean CD34 dose when comparing the group of patients who developed acute GVHD with the group that did not develop acute GVHD (P value: 0.31). Those who developed acute GVHD (n = 35) received a mean CD3 dose of 41.9 × 107/kg IBW (95% CI: 35.9–47.9). Those who did NOT develop acute GVHD (n= 32) received a mean CD3 dose of 33.5 × 107/kg IBW (95% CI: 27.3–39.8). By using the t-test, the P value for the different means was 0.0575. However, using a CD3 dose cutoff value of 30 × 107/kg IBW, the incidence of acute GVHD was statistically significantly less among those who received CD3 dose < 30 × 107/kg IBW. The Chi Square P value was 0.04. Conclusions: In our series, CD3 dose less than 30 × 107/kg IBW was associated with reduced risk of acute GVHD (P value: 0.04). There was no correlation between CD3 and CD34 counts in peripheral stem cell product. In addition, the CD34 dose did not influence the incidence of acute GVHD. These data suggest that, in addition to considering CD34 dose required for engraftment in allogeneic transplant, the CD3 dose will need to be considered to try to minimize the risk of acute GVHD. No significant financial relationships to disclose.

Autoimmune Haemolytic Anaemia after Allogeneic Haematopoietic Stem Cell Transplantation; Single Centre Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5675-5675
Author(s):  
Zar Ni Soe ◽  
Marina Karakantza ◽  
Beki James ◽  
Jennifer Clay ◽  
Amy Adams ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Haemolytic Anaemia ◽  
Haematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Haematopoietic Stem Cell ◽  
P Value ◽  
Cell Transplant

Haematopoietic stem cell transplantation (HSCT) typically involves manipulation or reconstitution of the immune system regardless of whether the cells are autologous or allogeneic. Consequently, there is a considerable risk of auto-reactive lymphocytes escaping central and peripheral immune tolerance, especially in a severely immune-depleted host, with subsequent development of new autoimmune diseases1. The mechanisms underlying this autoimmunity are still largely unknown. Autoimmune haemolytic anaemia (AIHA) is the most frequently reported autoimmune disease after stem cell transplant with an incidence of 1.3% to 4.4%2,3 in current literature. Potential reported risk factors have varied with different studies. We considered some previously reported risk factors for AIHA (ABO antigen mismatch, myeloablative (MAC) versus reduced intensity conditioning (RIC), matched sibling donor versus unrelated or haplo-matched donor, concurrent graft versus host disease (GvHD), Gender mismatch and CMV reactivation status) in 355 patients who underwent haematopoietic stem cell transplantation at our centre during the period October 2012 to October 2018. Patients who received autologous stem cells were excluded. Patient demographics are shown in Table 1. Results: Eleven out of 355 patients developed clinically and biochemically evident, direct antiglobulin test positive, AIHA (3.1% incidence). The median time to onset, from HSCT to AIHA, was 181 days. Details of AIHA patients are shown in table 2. Out of 355 patients, 179 had ABO antigen mismatched stem cell transplant (24 bidirectional, 82 major and 73 minor mismatched). Ten out of these 179 patients (5.6%) developed AIHA after transplant (2 out of 24 (8.3%) in bi-directional, 5 out of 82(6.1%) in major, 3 out of 73 (4.1%) in minor ABO mismatch group). One out of 176 patients (0.6%) who received an ABO matched stem cell transplant developed AIHA. This made the higher risk of AIHA in patients receiving ABO mismatched stem cell transplant compared with ABO matched counterpart statistically significant (RR 9.83(95%CI 1.3-76.0),p value=0.028). Six out of 106 patients (5.6%) developed AIHA in the MAC group and 5 out of 249(2.0%) in the RIC group. There was no statistically significant difference between MAC and RIC (p value=0.07). One hundred patients in our study received stem cells from matched sibling donors and none of them had evidence of AIHA after successful transplantation. In contrast, 11 out of 255 (4.3%) patients who received stem cells from unrelated donor or haplo-identical donors developed AIHA after transplant. However, there was not enough data for this trend to be statistically significant (p value =0.11). We also looked at the presence of concurrent GvHD as a possible risk factor for developing AIHA after transplant. Three out of 120 (2.5%) patients with GvHD and 8 out of 235 (3.4%) patients without GvHD developed AIHA. This was not statistically significant (p value=0.64). Similarly, there was no statistically significant association of post-transplant AIHA with gender mismatched donor transplant (p value= 0.78) or CMV reactivation status (p value= 0.13). Conclusion: Autoimmune haemolytic anaemia after stem cell transplantation is poorly understood due to the complex process of lympho-depletion, immunosuppression, immune reconstitution and graft versus host effects during and after successful transplantation. Our data show that receiving stem cells from ABO mismatched donor is a strong risk factor for developing autoimmune haemolytic anaemia after transplant. Further understanding of immune mechanisms underlying autoimmunity after stem cell transplantation will help to reduce the incidence of AIHA and to improve the overall survival. References: 1. Holbro A, Abinun M, Daikeler T, et al. Management of autoimmune diseases after haematopoietic stem cell transplantation. British Journal of Haematology. 2012;157, 281-290. 2. Sanz J, Arriaga F, Montesinos P, et al. Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients. Bone Marrow Transplant. 2007;39(9):555-561. 3. Wang M, Wang W, Abeywardane A, et al. Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital. Biol Blood Marrow Transplant. 2015; 21(1):60-66. Disclosures No relevant conflicts of interest to declare.

Finalization of autologous stem cell transplant in complex and multirelapsed follicular lymphoma

2020 ◽  
Vol 106 (6) ◽  
pp. NP5-NP8
Author(s):  
Matteo Carella ◽  
Vittorio Stefoni ◽  
Cinzia Pellegrini ◽  
Lisa Argnani ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
Stem Cell Transplant ◽  
Young Patients ◽  
High Dose ◽  
Cell Transplant ◽  
Aggressive Approach ◽  
Frequent Relapses

Background: Follicular lymphoma (FL) is characterized by frequent relapses and need for multitude lines of therapy, which includes different immunochemotherapy regimens, novel monoclonal antibodies, novel drugs, and autologous or allogenic stem cell transplant. Early use of autologous stem cell transplantation (ASCT) improves prognosis in patients with FL who may be candidates for an aggressive approach. Case presentation: We report the case of a 49-year-old woman with thrombophilia with relapsed/refractory grade 3A FL, heavily pretreated, who achieved third complete remission after high-dose chemotherapy and ASCT, despite experiencing life-threatening adverse events during her treatment history. Conclusions: Stem cell transplantation has emerged as the standard of care for young patients with FL but may be effective also in complex and multirelapsed clinical cases.

Incidence and Risk Factors for Thromboembolism in Patients with Hematologic Malignancies Undergoing Allogeneic and Autologous Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1141-1141
Author(s):  
Nicole M. Kuderer ◽  
Alok A. Khorana ◽  
Jonathan W. Friedberg ◽  
Eva Culakova ◽  
Gordon L. Phillips ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Stem Cell Transplant ◽  
Multivariate Logistic Regression Analysis ◽  
Hematologic Malignancies ◽  
Cell Transplant ◽  
Multivariate Logistic Regression ◽  
Transplant Patients

Abstract Background: Thromboembolism (TE) is a common complication of hospitalized non-transplant cancer patients. To date, the extent and impact of TE in stem cell transplant patients is unknown, in part because it is considered a low risk group given the high prevalence of thrombocytopenia. The purpose of this study is to evaluate the incidence of and risk factors for TE in cancer patients undergoing stem cell transplantation. Methods: We conducted a retrospective analysis of all discharge summaries from the 115 US academic health centers reporting to the University HealthSystem Consortium from 1995 to 2002. We identified a total of 7,087 patients with hematologic malignancies undergoing allogeneic and autologous stem cell transplantation. The incidence of and risk factors for venous and arterial TE was analyzed in univariate and multivariate logistic regression analysis with adjusted odds ratios as estimates of relative risk. Results: TE was reported in 389 (5.5%) transplant patients with 4.8% patients developing venous and 0.7% arterial TE. The incidence of TE was greater in allogeneic (6.8%) compared to autologous (4.8%) transplant patients (p&lt;0.0001). Among those receiving allogeneic transplantations, BMT patients experienced a higher rate of TE than PBSC patients (7.5% vs 5.6%; p&lt;0.05). In multivariate logistic regression analysis, the following clinical variables were significantly associated with TE in stem call transplant patients with hematologic malignancies: gram negative sepsis (OR=1.76; 1.02–3.02; p=0.04), gram positive sepsis (OR=1.75; 1.25–2.45; p=0.001), line infections (OR=1.48; 1.11–1.97; p=0.008), central venous catheters (OR=1.74; 1.39–2.17; P&lt;0.0001), pulmonary disease (OR=1.87; 1.47–2.37; p&lt;0.0001), liver disease (OR=1.31; 1.01–1.70; p=0.04) and length of stay &gt;30 days (OR=1.66; 1.30–2.13; p&lt;0.0001). Hodgkin’s disease (OR= 0.59; 0.37–0.94; p=0.026) was associated with a lower risk of TE. In multivariate analysis, the type of transplant failed to remain an independent risk factor for TE after controlling for other transplant complications. Conclusions: This is the first substantive report on the incidence of thromboembolism in stem cell transplant patients. We found that thromboembolic events are a frequent complication in patients with hematologic malignancies undergoing stem cell transplantation. The incidence of TE is high among most subgroups studied. Prospective studies are needed to evaluate the efficacy and safety of thromboprophylaxis in this high-risk population.

High (95%) Response Rates in Relapsed/Refractory Mantle Cell Lymphoma after R-HCVAD Alternating with R-Methotrexate/Cytarabine (R-M-A).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2446-2446 ◽  
Author(s):  
Jorge Enrique Romaguera ◽  
Luis E. Fayad ◽  
Michael Wang ◽  
Fernando Cabanillas ◽  
Fredrick Hagemeister ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Previous Treatment ◽  
Median Number ◽  
Cell Transplant ◽  
Mantle Cell

Abstract Mantle cell lymphoma (MCL) has a poor prognosis. Relapsed/refractory patients must respond to salvage chemotherapy in order to receive potentially curative stem cell transplantation (SCT). A salvage regimen with higher rate of response will offer the patient a better chance of survival. We have previously reported the results of R-HCVAD alternating with R-M-A in frontline therapy of MCL (Blood, 104:40a, 2004, (Abstract #128). The current trial looked at relapsed/refractory MCL patients treated also with R-HCVAD alternating with R-M-A. Since August 2001, the trial has accrued 24 out of a planned number of 41 patients of whom 21 are evaluable for response and survival. Median age was 63 years (range 45–78) and male:female ratio was 5:1. Three patients had received previous R-HCVAD alternating with R-M-A and three patients had failed an autologous stem cell transplant. Immediate therapy prior to the study for the 21 patients included R-HCVAD/SCT (1), CHOPw/wo rituximab (8 patients), cyclophosphamide, vincristine and rituximab (1), fludarabine (1), fludarabine, mitoxantrone, dexamethasone and rituximab (2), fludarabine and cyclophosphamide (1), radiotherapy (2), gemcitabine, mitoxantrone and dexamathasone (1) ifosfamide, carboplatin, etoposide and rituximab (1), Velcade (1), gemcitabine (1), and rituximab (1). The median number of prior regimens was one (range 1–6). Responses to the previous treatment included complete response (CR; 8 patients, 38%), partial response (PR; 6 patients, 29%), and no response or progression (7 patients, 33%). Results of the trial are as follows: Median number of cycles received = 4 (range 1–7), with an overall response rate (ORR) of 95% (43% CR/Cru; 52% PR). 5/5 patients who had progressed through the previous treatment responded (1CR, 4 PR), and 2/2 patients who had no change to the prior therapy responded (2 PR’s). We evaluated 12 cases whose response in our trial was classified as PR and found that in 4 of them it was the best response achieved but another 4 were referred to transplant while the tumor was still responding and in another case treatment was still ongoing. In 3 cases toxicity precluded continuation of therapy. Five (24%) of the patients were consolidated with non-myeloablative allogeneic stem cell transplantation. Sixteen were not transplanted for the following reasons: age (2 patients), lack of donor (5), Progressive disease (2), patient refusal (4), physician’s choice (1), waiting for match (1), and lost to follow up (1). Toxicity after 81 cycles included neutropenic fever (14%), grade 4 neutropenia (58%) and grade 4 thrombocytopenia (53%). The were no deaths due to toxicity. With a median follow-up of 21 months range 5–45 months), the median failure-free survival is 18 months as compared to a median FFS of 9 months response duration with the previous therapy, with no plateau in the curve. Patients who underwent stem cell transplant were censored at the time of transplant. The high response rates achieved R-HCVAD alternating with R-M-A makes this regimen an excellent choice for induction therapy prior to stem cell transplantation.

Norovirus Infections in Patients with Hematological Diseases and After Stem Cell Transplantation; Epidemiological and Clinical Aspects.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2661-2661
Author(s):  
Per T. Ljungman ◽  
Per Bernell ◽  
Richard Lerner ◽  
Jonas Mattsson ◽  
Maria Rotzén Östlund ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Duration ◽  
Stem Cell Transplant ◽  
Positive Sample ◽  
Clinical Aspects ◽  
Cell Transplant ◽  
Hematological Diseases ◽  
Virus Excretion

Abstract Abstract 2661 Poster Board II-637 Norovirus infections have become a major practical clinical problem during the last few years causing outbreaks in many different situations including in hospitals infecting both patients and staff. These infections have also been associated with prolonged virus excretion in renal transplant recipients and a risk of mortality in the elderly. Little is known about the clinical impact of norovirus infections on patients who are severely immunosuppressed. The aim of this study was to analyze the impact of norovirus infections in patients with hematological diseases and after hematopoietic stem cell transplantation (HSCT). The laboratory records from the Clinical Microbiological Laboratory at Karolinska University Hospital were examined in order to identify patients with proven norovirus infection hospitalized on the haematology or allogeneic stem cell transplant wards from 2006 to 2009. The diagnostic methodology was based on an accredited protocol including a reverse transcription real- time PCR procedure with the use of oligonucleotide primers specific for detection of norovirus genotype 1 or 2 in separate wells. After identification of cases, the patient charts were reviewed to assess outcome, possible norovirus associated clinical complications, and delay of antitumor therapy. The duration of virus excretion was defined as the time from the first to the last positive sample. 65 patients were identified. 19 patients had NHL, 14 AML, 8 multiple myeloma, 8 non-malignant hematological disorders, 5 ALL, 5 CLL, 4 MDS, and one patient had CML. 24 patients had undergone HSCT; 22 allogeneic and 2 autologous. The median age was 63.1 (1.1–84.2). The cases occurred in two major and 3 minor clusters over the 3 year period with some additional sporadic cases occurring between the clusters. One of the haematology wards had to be closed for admission twice and one ward once since also several cases occurred among the staff. 17 of the detected viruses were typed to genogroup 2, 2 to genogroup 1, and 46 were not typed. 29 patients had only one positive sample of which 11 had a negative follow-up sample. The median duration of viral detection in the entire cohort was 2 days (1–216 days). Among the patients with more than one positive sample, the median duration was 15 days (2–216 days). 25/65 (38%) patients were PCR positive more than one week, 18 (28%) for more than two weeks, and 9 (14%) for more than four weeks. The majority of patients had minor and quickly resolved gastrointestinal symptoms. Five patients died in close temporal association with the norovirus infection (within a week). Three patients had fluid balance and electrolyte abnormalities and in of these a pre-existing renal failure worsened and the patient required dialysis. One patient died from pneumonia and one patient died from multiple causes with an end-stage malignancy. Seven patients (11%) had planned cytotoxic chemotherapy postponed; one of these patients had a delay in a planned allogeneic HSCT. We conclude that norovirus infection is a significant clinical complication to management of patients with hematological malignancies and stem cell transplant patients. Fatal outcome is possible primarily in patients with severe underlying conditions. Delay in planned chemotherapy was common and in addition the required closing of the ward presumably delaying chemotherapy for other non-infected patients. Disclosures: No relevant conflicts of interest to declare.

Phase I Study of Eltrombopag for Promoting Thrombopoiesis in Patients Undergoing Stem Cell Transplantation After Total Body Irradiation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 219-219 ◽  
Author(s):  
Jane L. Liesveld ◽  
Gordon L. Phillips ◽  
Michael W. Becker ◽  
Louis Constine ◽  
Jonathan W. Friedberg ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Phase I ◽  
Cell Transplantation ◽  
Dose Level ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Once Daily ◽  
Total Body

Abstract Abstract 219 Purpose: Prolonged intervals of thrombocytopenia are common after stem cell transplantation, and platelet transfusions are the only temporary therapy before engraftment. Risk of thrombocytopenia is greater in patients receiving total body irradiation (TBI) in their conditioning regimen. Eltrombopag is a small-molecule, nonpeptide oral agent that functions as an agonist of the thrombopoietin receptor. It is approved by the FDA for the treatment of chronic idiopathic thrombocytopenic purpura and is being developed as a treatment for thrombocytopenia of other various etiologies. We report updated results of a Phase I clinical trial assessing the safety, pharmacokinetics (PK) and maximum tolerated dose (MTD) of once daily oral eltrombopag in patients undergoing stem cell transplantation with a conditioning regimen containing TBI ≥ 400 cGy. Methods: A Phase I dose-escalation clinical trial was conducted to evaluate the safety and PK of eltrombopag at 4 different dose levels: 75, 150, 225, and 300 mg given once daily for 27 days, starting 24–48 hours post stem cell transplantation to eligible patients ≥18 years old. Patients with various indications for stem cell transplantation, KPS ≥70%, and TBI ≥ 400 cGy were eligible. Patients receiving either an autologous (Auto) or allogeneic (Allo) stem cell transplantation from a sibling, related donor, or matched unrelated donor (MUD) were eligible. Stem cells from peripheral blood (PBSC) or bone marrow were permitted; however, cord blood stem cell transplantation was not permitted. Patients at risk of thromboembolism or with a history of thromboembolic disease in the preceding 6 months were excluded. PK sampling was obtained over a 24 hour period after the first dose of eltrombopag as well as during the second week of treatment (steady-state). Results: As of August 1 2012, a total of 19 subjects (7 AML, 4 lymphoma, 1 CML, 1 MDS, 1 myelofibrosis, 2 ALL, 1 APML, 1 Biphenotypic Leukemia and 1 CLL/SLL) were enrolled, and 15 completed protocol treatments. All 19 were PBSC transplants with 12 MUD, 6 Allo and 1 Auto. Three subjects were completed at each dose level up to 225 mg with six completing treatment at the highest dose of 300mg. Four subjects were replaced because drug compliance was less than 75%. To date, 11/19 are alive while 8/19 have died (3 related to graft vs. host disease (GVHD), 3 Infection-related and 2 related to disease progression (f/u interval: 5.7 – 30 months). No dose limiting toxicities (DLTs) have been observed. The most common adverse events (AEs) up to the 300 mg dose level were related to standard stem cell transplantation, which included low blood counts, fatigue, headache, diarrhea, nausea, peripheral edema, hypoalbuminemia, hyperglycemia, hypocalcemia, and hypomagnesemia. Possibly drug-related AEs were dry skin, rash, elevated creatinine, and hypokalemia; these were all grade 3 or less. There were 12 severe AEs observed in 8 subjects, which included infection (3/19), pulmonary embolism (PE) (1/19), acute renal failure (3/19), gastrointestinal (2/19), acute respiratory distress syndrome (1/19), pericarditis (1/19) and GvHD skin rash (1/19). Most SAEs were considered related to stem cell transplant, except one subject at 75 mg with PE possibly related to eltrombopag, but also possibly related to stem cell transplant and cancer diagnosis. The PE occurred 9 days after stopping eltrombopag at which time platelet count was 252K. Time to platelet engraftment and number of platelet transfusions were also documented for each enrolled patient. Median time to platelet engraftment for all subjects on this study was 16 days. PK data are summarized in Table 1 and Figure 1. A dose-dependent increase in plasma exposure of eltrombopag was observed; although some saturation of absorption is evident at the 300 mg dose level. (Figure 1). Conclusions: 27-day once daily dosing of eltrombopag to enhance platelet recovery for post-transplant thrombocytopenia is well tolerated, with no DLTs observed up to the 300 mg dose level. Most AEs were transplant related. PK showed proportional plasma concentration up to 225 mg daily dosing, with some saturation of drug absorption above 225 mg. Disclosures: Liesveld: Eisai: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Ariad: Honoraria. Off Label Use: Eltrombopag not approved post-transplant. Dawson:GlaxoSmithKline: Employment.

Outcomes of Autologous Stem Cell Transplantation for Lymphoma in the Elderly: A Single Center Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5505-5505
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Shaun DeJarnette ◽  
Clint Divine ◽  
Tara L Lin ◽  
Leyla Shune ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Pulmonary Toxicity ◽  
Stem Cell Transplant ◽  
The Elderly ◽  
Median Number ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract INTRODUCTION: Autologous stem cell transplant (ASCT) is a potentially curative option for lymphoma, yet there remains a bias against offering this therapy to the elderly. Patients above age 65 are nearly always excluded from clinical trials with ASCT, limiting our understanding of the efficacy and toxicities of ASCT in this population. This lack of data and bias against ASCT in the elderly may delay referral for patients who may benefit from a transplant. Here, we report our single institution outcomes from all patients aged 65 and greater who underwent autologous stem cell transplant for lymphoma at our institution. DESIGN AND METHODS : We identified 93 consecutive patients ³ 65 years of age (median age 68.6 years) with lymphoma who underwent autologous stem cell transplantation at University of Kansas Medical Center from 2000 to 2015. After IRB approval, data was extracted using the institutional database. These patients had frequently received at least two treatments, were often beyond first complete remission at the time of transplantation and received their transplants later after diagnosis. Table 1 below summarizes the pre-transplant characteristics of our patients. RESULTS: All patients received G-CSF mobilized peripheral blood stem cells. Engraftment data is available for 87 out of 93 patients. Median number of days to neutrophil recovery (Absolute neutrophil count >500) was 11 (range 9-14). Median number of RBC and platelet transfusion in this group was 2 (range 0-10) and 3 (range 0-39), respectively. Non-relapse mortality at 100 days for the entire group was 2.15%. Overall survival at 100-days was 96.8%. Three patients (3.2 %) developed grade IV pulmonary toxicity and one patient developed grade IV veno-occlusive disease. With a median follow up of 744 days (41-2431), a disease free survival of 373 days was noted. In 63 patients who underwent transplant prior to 2013, 1-year and 2-year overall survival was found to be 84.2% and 72.1 respectively. Of the deaths in first year, 6 (55%) were related to relapse/progression, two (18%) due to pulmonary toxicity, 2 (18%) due to cardiac toxicity and 1 (9%) due to infection. In 17 patients (18.2%), transplant was performed completely/partially as an outpatient procedure. CONCLUSIONS: Although retrospective in nature, these results suggest that transplant related mortality in elderly patients with lymphoma is similar to historic younger cohorts. Chronological age should not be used alone in evaluating lymphoma patients for autologous stem cell transplantation. Instead, a comprehensive evaluation using Hematopoietic cell transplant comorbidity index and geriatric assessment should be used to guide decision-making. As the elderly population grows, an individualized approach to each patient considering all available treatment options is needed to make a potentially curative ASCT for high risk or relapsed lymphoma available to more patients. Table 1. No of patients (%) GenderMale Female 60 (65) 33 (35) Age at ASCT, median (range) 68.6 ( range 65-80) Hodgkin Disease Non Hodgkin Disease 5 (5) 88 (95) NHL subtypes Diffuse Large B- Cell Lymphoma Mantle Follicular Other 35 (40) 18 (20) 16 (18) 19 (22) Disease Status at ASCTCR1 CR 2 or more CRU PR Relapse1 Relapse 2 or more Primary Refractory 29 (31.2) 29 (31.2) 6 (6.5) 19 (20.4) 5 (5.4) 2 (2.2) 3 (3.2) Response to most recent chemoComplete remission Partial remission Progressive disease 64 (68.9) 19 (20.4) 10 (10.8) HCT-CI (% from those with obtained data) 0 1-2 3 or more N/A 15(19.0) 23(29.1) 41(51.9) 14 Disclosures No relevant conflicts of interest to declare.

ESHAP+/− Rituximab as Salvage Therapy for Relapsed Lymphoma Prior to Stem Cell Transplant: Single Institution Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4601-4601 ◽  
Author(s):  
Sagun Shrestha ◽  
Christina Johnson ◽  
Sanjeev Jain ◽  
Dilip V. Patel ◽  
Bhoomi Mehrotra
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Salvage Therapy ◽  
Progressive Disease ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Non Hodgkins Lymphoma ◽  
Disease Free

Abstract OBJECTIVE: High dose chemotherapy with stem cell transplantation (ABMT) has become the standard treatment for relapsed aggressive non-Hodgkins and Hodgkins Lymphomas. However, there is no one salvage therapy accepted as a standard regimen prior to ABMT. ESHAP, as a combination chemotherapy regimen consisting of Etoposide, Methylprednisolone, Cytosine arabinoside, and infusional Cisplatin, has been shown to be an active regimen for the treatment of refractory Non-Hodgkins Lymphoma in previously published trials. The objective of this study was to determine the efficacy of ESHAP with and without Rituximab as a cytoreductive regimen in relapsed lymphomas prior to stem cell transplant. METHODS: This retrospective study was approved by the Institutional Review Board. Patients with relapsed Hodgkins and Non-Hodgkins lymphoma who were treated at our institution between March 1997 and July 2004, with the intent of proceeding to ABMT after obtaining a complete remission and were treated with ESHAP containing salvage regimen, were included in this study. Data collection was done by review of all pertinent medical records. RESULTS: Twenty four patients with relapsed lymphomas were identified that were treated with ESHAP +/− Rituximab during this period, with the intent to proceed with ABMT after achieving a maximal response. Histology included: large cell lymphoma (n=15), mantle cell lymphoma (n=3), and Hodgkin’s disease (n=6). Median age was 54 years and male-to-female ratio was 1.4:1. Staging of disease at the time of initial diagnosis was done by PET scan, CT scans, and bone marrow examination. Staging at time of salvage treatment for relapsed disease: stage I (n=1) stage II (n=2)), stage III (n=12), stage IV (n=9). Prior treatment consisted of CHOP, ABVD, TVC, MOPP/ABVD, CNOP, CVP, and CAV. The median disease free interval prior to salvage therapy was 12 months. Of 24 patients, 17 received ESHAP and 7 received ESHAP+ Rituximab as salvage therapy. The median time to transplant after initiation of salvage therapy was four months. Nineteen of twenty four patients (79%) proceeded to receive stem cell transplantation. Five patients did not proceed to ABMT secondary to failure to achieve a complete remission or had progressive disease. Patients treated with ESHAP + rituximab compared to ESHAP alone had no evidence of altered transplant related morbidity, as measured by time to engraftment, duration of hospitalization and the number of episodes of febrile neutropenia. No treatment related mortality occurred in all patients. Of the patients who underwent ABMT, 53% are disease free at a median follow up of 48 months. Among those who did not receive stem cell transplant, 4 died of progressive disease, and one has no evidence of disease in 12 months of follow up. CONCLUSIONS: ESHAP with and without Rituximab is an effective and a feasible salvage therapy for patients with relapsed lymphomas when used as a cytoreductive regimen prior to stem cell transplantation and does not negatively impact on transplant treatment related morbidity and mortality. Further studies are necessary to compare its efficacy with other standard salvage regimens prior to ABMT.

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