Genetic polymorphisms associated with clostridium difficile infection in multiple myeloma patients undergoing autologous stem cell transplantation.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8522-8522
Author(s):  
Issam Hamadeh ◽  
Zainab Shahid ◽  
Manisha Bhutani ◽  
Jai Narendra Patel ◽  
Nury Steuerwald ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Stem Cell ◽  
Antibiotic Prophylaxis ◽  
Conditioning Regimen ◽  
High Dose ◽  
Host Immune System ◽  
Cell Transplant ◽  
Regression Analyses ◽  
Multivariate Logistic Regression ◽  
Buccal Swabs

8522 Background: CDI is the primary cause of infectious diarrhea in immunocompromised patients including those undergoing autologous stem cell transplant (SCT). Given the key role of gut microbiome and its interaction with host immune system, we investigated whether polymorphisms in innate immunity genes (identified through Ingenuity Pathway Analysis) were associated with CDI. Methods: We queried our database to identify MM patients who underwent an autologous SCT between April 2015-June 2019. Patients who had their buccal swabs collected through an IRB approved specimen collection protocol were included herein. Data were collected on age, conditioning regimen, CDI diagnosis, time from admission until CDI diagnosis, absolute neutrophil count (ANC) at time of CDI diagnosis, and antibiotic prophylaxis. Genomic DNA was extracted from buccal swabs and genotyped for 62 single nucleotide polymorphisms (SNPs) in ASPH , RLBP1L1, ATP7B, IL-8, FAK, TNFRSF14, CTH, TLR and IL-4. Univariate and multivariate logistic regression analyses were performed to assess association between CDI and presence of SNPs in these genes. Results: A total of 83 patients were identified (25 cases and 58 controls). Baseline characteristics were comparable between two groups. Median age was 67 years (range: 50-79). All patients received high dose melphalan as conditioning, and the same antibiotic prophylaxis during peri-transplant period. Median time from hospitalization until CDI diagnosis was 10 days (IQR:9 days), and median ANC was 0.7/mL (IQR:1.6/mL). Two SNPs (rs2227307 T > G in IL-8 and rs2234167 G > A in TNFRSF14) were significantly associated with CDI risk in both univariate and multivariate logistic regression analyses (Table). Conclusions: Our findings suggest that rs227307G (in IL-8) and rs2234167A (in TNFRSF14) alleles are potential risk factors for CDI after autologous SCT. Our findings, if validated in a larger cohort, would support genetic testing as a screening tool to identify patients who might benefit from prophylaxis against CDI. [Table: see text]

Outcomes Following Autologous Stem Cell Transplantation (ASCT) In Patients With Germinal Center B (GCB) and Non-GCB Cell-Like Diffuse Large B Cell Lymphomas (DLBCL) According To Conditioning With BEAM-Rituximab (Standard vs. High-Dose) Vs. BEAM/Yttrium-90 Ibritumomab Tiuxetan (90YIT)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3350-3350
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Zijun Y Xu-Monette ◽  
Gabriela Rondon ◽  
Rosamar Valverde ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Cell Of Origin ◽  
Ibritumomab Tiuxetan ◽  
Bone Marrow Biopsies ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
The Impact

Abstract Background Patients with a DLBCL of GCB immunophenotype have a higher chance of cure than patients with non-GCB DLBCL when treated with conventional chemotherapy. In the relapsed/refractory setting, there are conflicting data regarding the impact of cell-of-origin classification on survival following ASCT. The addition of high-dose rituximab (HDR) (1000 mg /m2 days +1 and +8 after ASCT) has been shown to improve results for patients with relapsed DLBCL who undergo transplantation (Khouri et al, J Clin Oncol 2005;23:2240-7). The optimal rituximab dose to be used with ASCT [HDR vs. standard dose (SDR) 375 mg/m2 days +1 and +8)] has been under investigation at our center. More recently, we and others reported on the safety of incorporating 90YIT (0.4 mCi/Kg) in the conditioning. Herein, we compare outcomes of patients with GCB and non-GCB DLBCL after ASCT according to the conditioning regimen received. Methods and patients 121 de novo DLBCL patients were treated on 4 consecutive trials between 2000 and 2012. We determined the cell-of-origin, based upon the Visco/Young and Choi immunohistochemical algorithms, and classified 64 (53%) as GCB and 57 (47%) as non-GCB tumors. Median age, gender distribution, remission status (CR vs PR), # of prior therapies, IPI, beta-2 microglobulin and LDH distribution were similar in both groups. Patients were staged with CT, PET (whenever indicated) scans and bone marrow biopsies, every 3 months for the first year, every 6 months x 5 years, then yearly thereafter. Patients received BEAM conditioning with either SDR [GCB (n =14), non-GCB (n=7), HDR [GCB (n =31), non-GCB (n=40) or 90YIT[GCB (n =19), non-GCB (n=10)]. Results Determinants for progression (cell-of-origin, age, and gender, and disease status, # of prior therapies, IPI, beta-2 microglobulin and LDH distribution) were studied within each type of conditioning. Within the BEAM-SDR group, the cell-of-origin was the only significant predictor for relapse at 3-years (86% in non-GCB vs. 14% in GCB; P=0.01) (Figure), resulting in improved OS and PFS for the GCB group (both 71% vs 14%, respectively, P=0.06 for OS and 0.04 for PFS). Non-relapse mortality was 0% in this group. Within the BEAM-HDR and BEAM-90YIT groups, GCB and non-GCB patients had a similar rate of relapse (30% vs. 38%, respectively at 3-year, P=0.4) and similar 3-year PFS rates 66% vs 56%, P=0.3), and 3-year OS of 77% vs. 61% (P=0.09). Conclusion Our results suggest similar outcomes for patients with DLBCL of GCB and non-GCB immunophenotype when either HDR or 90YIT is added to the BEAM conditioning. A SDR has been found to be associated with a significantly higher risk of progression and inferior survival in non-GCB patients. Disclosures: Khouri: Spectrum Pharmaceuticals: Consultancy, Research Funding. Off Label Use: Rituximab and ibritumomab tiuxetan for stem cell transplant.

Single Autologous Stem Cell Transplant Using Busulfan and Cyclophosphamide as Conditioning Regimen in Patients with Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4436-4436
Author(s):  
Giampaolo Talamo ◽  
David F. Claxton ◽  
Joseph Drabick ◽  
David W. Dougherty ◽  
Jeff Sivik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Single Agent ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Transfusion Threshold ◽  
Significant Difference ◽  
High Dose Melphalan

Abstract Autologous peripheral blood stem cell transplantation (ASCT) has been shown to improve survival in patients with multiple myeloma (MM). High-dose melphalan is considered the current standard of care among the preparative regimens used in ASCT for MM patients. We report the results of ASCT in 79 consecutive MM patients using a conditioning regimen with busulfan and cyclophosphamide (Bu/Cy), given as single ASCT and without maintenance therapy. Peripheral blood stem cells were mobilized with cyclophosphamide 5,000 mg/m2 IV + etoposide 1,000 mg/m2 IV, followed by granulocyte colony stimulating factor (G-CSF) 5 mg/Kg/day until the end of stem cell collection. A median of 41.1 × 106 CD34+ cells/Kg (range, 2.1–139.7 × 106) of ideal body weight were mobilized. The conditioning regimen consisted of busulfan 1 mg/Kg PO or 0.8 mg/Kg IV every 6 hours x 16 doses (days -7 to -3), and cyclophosphamide 60 mg/Kg/day IV for 2 days (days -3 to -2). Patients achieved neutrophil engraftment (absolute neutrophil count >500/μL) at a median of +13 days (range, +6 to +21 days), and platelet engraftment (platelets >20,000/μL unsupported by transfusion) at a median of 14 days (range, +11 to +24). Using a transfusion threshold of hemoglobin <8.0 g/dL and platelets <10,000/μL, patients required a median of 2 units of RBC transfusions (range, 0–8), and 1 platelet transfusion (range, 0–15) until hematologic engraftment. Forty-eight and 20 patients reached PR and CR, respectively, for an overall RR of 86%. At a median followup of 41 months (range 2–132 months), the estimated median overall survival (OS) and progression-free survival (PFS) were 45 months [95% confidence interval (CI) = 38–92] and 20 months (95% CI = 15–25), respectively. Veno-occlusive disease developed in 4 pts, and it was lethal in 1 of them. The Bu/Cy regimen was overall well tolerated, and transplant-related mortality was 4%. No statistically significant difference in terms of OS and EFS were observed between the group of patients receiving oral (n=13) vs IV busulfan (n=66). OS was not statistically different between the group receiving ASCT in first remission (n=62) and the group receiving ASCT as salvage therapy, i.e., upon MM progression (n=17), either calculating OS from the day of ASCT or from the day of MM diagnosis. We conclude that our reported clinical outcomes of the Bu/Cy regimen are equivalent to those obtained in historical controls with high-dose melphalan followed by a single ASCT. Thus, given the equivalent effectiveness but greater complexity of administration of the Bu/Cy regimen compared with that of single agent melphalan, we believe the latter should remain the agent of choice for ASCT in MM.

Combination Therapy with BCNU/Etoposide/Melphalan (BEM) as Conditioning Regimen for Autologous Stem Cell Transplant In Multiple Myeloma.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4587-4587
Author(s):  
Shanshan Liu ◽  
Ann Mohrbacher ◽  
Dan Douer ◽  
Vishesh R Kothary ◽  
Lisa Hanna ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
High Dose ◽  
Cell Transplant ◽  
Lytic Bone Lesions

Abstract Abstract 4587 Background: High-dose chemotherapy and autologous stem cell transplant (ASCT) remains an important therapeutic modality for MM patients. Traditionally high-dose single agent melphalan (200 mg/m2; Mel-200) has been used as the conditioning regimen prior to ASCT for MM. We investigated the combination regimen of BCNU, etoposide and melphalan (BEM) in this setting at our center. Methods: All patients who had undergone ASCT for MM utilizing BEM conditioning regimen at Norris Cancer Center, University of Southern California, Los Angeles were eligible. BEM consisted of BCNU 12 mg/kg (actual body weight or ideal body weight whichever was lower) iv on day -5, etoposide 60 mg/Kg iv on day -3, and melphalan 140 mg/m2 iv on day -1, prior to stem cell reinfusion on day 0. Overall survival (OS) was defined as time from MM diagnosis to death, or in patients still alive, the date of last follow-up. Progression-free survival (PFS) was defined as time from ASCT to date of relapse, or in patients without documented relapse, date of death or last follow up, whichever was sooner. Survival for patients with different clinical and disease-specific characteristics was explored using logrank test. Response was assessed according to International Uniform Response Criteria for MM. Results: A total of 44 MM patients underwent ASCT utilizing the BEM conditioning regimen. Of these, evaluable data was available for 42 patients (25 males; 60%, 17 females; 40%) with a median follow up of 27.6 mths. Median age at diagnosis was 54.5 yr (range 34–68) while median time from MM diagnosis to ASCT was 10.5 mths (range 2.8–47.8). MM subtypes included IgA (n=5, 12%), IgG (n=30, 71%) and light chain-only (n=7, 17%). Median bone marrow (BM) plasmacytosis at diagnosis was 42.5% (range 0%-100%). Durie-Salmon (DS) stages included stage I (12%), II (36%) and III (52%), while 4 patients (10%) had renal dysfunction at the time of initial MM diagnosis. Majority of the patients (71%) had lytic bone lesions at the time of diagnosis and 86% (n=36) hade secretory disease. Patients had received a median of 1 prior treatment (range 1–5), while 23 (55%) patients had received novel agents (proteasome inhibitors or IMiDs) prior to the BEM regimen. Response rates prior to and after the regimen are summarized in Table 1. After BEM-ASCT an additional 16 (38%) patients achieved a CR. Median duration of hospitalization and time to engraftment were 19 days (range 15–41) and 10.5 days (range 7–19), respectively. One patient died prior to discharge from the hospital post ASCT (Day 36 post ASCT) for a treatment related mortality of 2%. CR rate post BEM-ASCT was 64% with an ORR of 97%. Relapses have been noted in 25 patients to date. Median OS for all patients was 4.9 yrs (5.6 yrs for patients in CR and 6.6 yrs for patients in PR after BEM-ASCT). Median PFS was 23.9 mths for all patients (25 mths for patients in CR and 21.8 mths for those in PR after BEM-ASCT). No statistically significant differences were noted in OS based on patient gender (p=0.47), age at diagnosis (< or ≥60 yr), MM subtype (p=0.52), DS stage at diagnosis (0.09), patients without lytic bone lesions at diagnosis (p=0.054), secretor status (p=0.2), response status at the time of BEM-ASCT (p=0.9) or prior exposure to novel agents (p=0.62). Conclusions: BEM is a well-tolerated conditioning regimen prior to ASCT in MM and has efficacy comparable to Mel-200. BEM can be effectively employed in patients where Mel-200 is not feasible. We are particularly intrigued by its ability to deliver high CR rates (64%) compared to <30% (historical control). Very encouraging median OS (4.9 yr) and PFS (23.9 mth) rates were noted which were even better in patients who had a measurable response after this regimen. Further investigations will be needed to optimally define its potential as standard conditioning regimen in MM patients undergoing ASCT. Disclosures: No relevant conflicts of interest to declare.

PK-Directed Intravenous Busulfan In Combination With High-Dose Melphalan and Bortezomib As Conditioning Regimen For Patients With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5513-5513
Author(s):  
Stefan K Barta ◽  
Amitabha Mazumder ◽  
Jason Carter ◽  
Lawrence Almanzar ◽  
Richard Elkind ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Treatment Dose ◽  
Gi Symptoms ◽  
High Dose Melphalan

Abstract Introduction High dose therapy followed by autologous hematopoietic stem cell transplantation (ASCT) has an established role in the treatment of patients with multiple myeloma (MM). The most commonly used conditioning regimen in this setting is high-dose melphalan (200mg/m2; Mel200), which has been shown to result in improved progression free (PFS) and overall survival (OS). Achievement of a complete response (CR) following ASCT is an indicator for freedom from relapse, as well as PFS and OS. The CR rate observed after Mel200 followed by ASCT is between 10-35%. There is evidence that the combination of busulfan (Bu) and melphalan (Mel) results in longer PFS and OS compared to Mel alone. Additionally, the use of bortezomib (Btz) during conditioning with either high dose Mel alone or the combination of Mel and intravenous (i.v.) Bu has shown to be both safe and to have promising efficacy. The objective of our trial is to assess whether the combination of PK-directed Bu, Mel and Btz (BuMelBtz) during conditioning for a first ASCT in MM patients is both safe and efficacious. Methods Patients aged 18-72 with multiple myeloma, who had 1) measurable disease, 2) received less than one year of prior myeloma-directed therapy, 3) adequate organ function and performance status, and 4) an indication for ASCT were eligible. Exclusion criteria were >/= grade 2 neuropathy, prior stem cell transplant, uncontrolled intercurrent illnesses or comorbidities, unresolved >/= grade 2 toxicities from prior therapies, and prior malignancies except non-melanoma skin cancer. Treatment consisted of PK-directed i.v. Bu (4 daily 3-hour infusions from day (D) -6 to -3 to target a total AUC of 20,000 μMxmin), i.v. Mel 140mg/m2 on D-2, and i.v. Btz 1.4mg/m2 on D-6, -4, +1 and +4. The individual daily doses for Bu on D-6 and D-5 were determined by PK measures following a test dose (0.8mg/kg) 5-9 days prior to first Bu treatment dose; the last 2 doses (day -4 and -3) could be adjusted following another PK measure after the first full treatment dose on D -6. Stem cells were infused on D0. Subsequent consolidative or maintenance therapy was left to investigator choice. Primary outcome was CR rate assessed on D +100 post ASCT as per IMWG criteria. Secondary outcomes were overall response rate (ORR), toxicities, PFS and OS. The trial is registered at clinicaltrials.gov (NCT01605032). Results To date, 13 patients have been treated. The median age was 63 years (range 44-70), 62% (n=8) were male, 23% had ISS stage 3 (3/13), no patient had high risk cytogenetic features. The median number of regimens prior to ASCT was 1 (range 1-3) and included bortezomib in 92% (n=12). Prior to BuMelBtz the best treatment response had been stable disease (SD) in 3 patients, partial response (PR) in 8; only 1 patient each had achieved a very good partial response (VGPR) or CR. Following BuMelBtz/ASCT, median days to ANC >/=0.5 x 109/L and platelet count >/=30 x 109/L were 11 (range 10-13) and 17 (11-29), respectively. The most common non-hematological toxicities were alopecia (100%), oral mucositis (62% G3), dysphagia (85% G3, but no patient required TPN or enteral feeding), as well as electrolyte abnormalities (62% G3/4). Other common toxicities were nausea (92%, all G1/2), diarrhea (84% G1/2, 8% G3), while 77% of patients developed fully reversible transaminitis (15% G3). Less common G3 toxicities included delirium (8%), colitis (8%), skin infection (zoster, 8%), other infections (23%), and delirium (8%). One patient developed GI symptoms suggestive of acute GVHD on a gastric biopsy 8 weeks after ASCT. No patient developed sinusoidal obstruction syndrome of the liver. At 100 days post BuMelBtz/ASCT, response assessment was available for 8 patients: 1 achieved a stringent CR (12.5%), 4 VGPR (50%), and 3 PR (37.5%), resulting in a 100% ORR. One patient improved from a VGPR to a stringent CR during follow up. After a median follow up of 5 months (range 1-15) all patients are alive and no patient has relapsed. The trial is ongoing. Conclusion PK directed i.v. Bu in combination with Mel and Btz (BuMelBtz) is an effective and safe conditioning regimen for patients with multiple myeloma. Further evaluation is warranted. Disclosures: Barta: Otsuka: Research Funding; Onyx: Honoraria, Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Honoraria. Off Label Use: IV Busulfan for the treatment of multiple myeloma.

Consolidative Autologous Stem Cell Transplant for Double Hit Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3993-3993 ◽  
Author(s):  
Andy I Chen ◽  
Craig Okada ◽  
Nate Gay ◽  
Phil Reiss ◽  
Stephen Spurgeon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Treatment Algorithm ◽  
B Cell Lymphoma ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Double Hit Lymphoma ◽  
Double Hit

Abstract Double hit lymphoma (DHL), defined as B cell lymphoma with a c-MYC rearrangement plus a IGH/BCL2 rearrangement, confers a poor prognosis. Outcomes with R-CHOP are dismal with reported 2 year EFS <30% in multiple series. To improve upon these results, Burkitt type regimens such as R-HyperCVAD and dose adjusted (DA) R-EPOCH have been attempted, but 2 year EFS remains < 50% in early reports. In addition, the SWOG-9704 study found a benefit for consolidative autologous stem cell transplant (autoSCT) in high risk DLBCL, likely including some DHL, although this reported benefit has not been confirmed in three other randomized European studies. Since 2010 the treatment algorithm at Oregon Health & Science University for fit patients with DHL has been DA-R-EPOCH followed by consolidative autoSCT in responding patients. Here we report the first 16 patients treated with consolidative autoSCT. At diagnosis, the median age was 58, and the median IPI was 3. All patients had rearrangements of c-MYC and IGH/BCL2. One of the c-MYC rearrangements was a classical t(8;14); the translocation partners in the other cases were unknown. Three patients also had a ‘triple hit’ with an additional BCL6 rearrangement. Fourteen patients received DA-R-EPOCH with intrathecal prophylaxis for induction. One received R-CHOP at another institution, and one received R-HyperCVAD. 15 of 16 patients were in CR after induction. Stem cell mobilization was performed with G-CSF +/- plerixafor, and BEAM was utilized as the high dose conditioning regimen. With a median follow-up of 18 months, the estimated 2 year PFS is 91 %, and the 2 year OS is 91 % in the 16 patients who underwent consolidative autoSCT. There were no deaths from non-relapse mortality, and the only relapse was 6 months post-transplant. All other patients undergoing autoSCT remain alive and in remission. An additional 15 patients also underwent induction with DA-R-EPOCH but did not proceed to autoSCT. Four patients who had intended to undergo autoSCT were refractory to induction. Of the remaining 11 patients, 9 did not pursue autoSCT because of age and/or comorbidities, and 1 each declined out of personal preference or insurance denial. Four of these 11 have relapsed or died. Our results suggest that consolidative autoSCT, especially after DA-R-EPOCH induction, is an effective treatment strategy for DHL in fit patients and should be explored in prospective studies. Disclosures No relevant conflicts of interest to declare.

Incorporating Target Immunotherapy into Standard Conditioning Regimen Prior to Autologous Stem Cell Transplantaion (ASCT) Improves the Transplant Outcome for Pateints with Relapsed/Refractroy B Cell Non-Hodgkin Lymphoma (B-NHL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1911-1911
Author(s):  
Mohamed I. Farhat ◽  
Reem Karmali ◽  
Stephanie A. Gregory ◽  
Parameswaran Venugopal ◽  
Mohamad Kassar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Background: Refractory or relapse B-NHL has a poor prognosis with conventional chemotherapy. Autologous stem cell transplant (ASCT) preceded by high dose chemotherapy has been the preferred therapeutic choice for such patients. The majority of the treatment failures occur within one to two years post transplant with disease progression after transplant accounted for most of the failures. The incorporation of targeted immunotherapy (rituximab) into the upfront and relapse setting is becoming of the standard of care for patients with B-NHL. The objective of this study is to evaluate the impact of rituximab (R) on disease free survival (DFS) when added to a standard conditioning regimen -- BEAM (carmustine, cytarabine, etoposide, and melphalan) prior to ASCT. Methods: A single institution retrospective analysis of 53 patients (pts), whom were heavily pre-treated, underwent ASCT between 08/98 & 07/06. All pts received rituximab in combination with high dose cytoxan for stem cell mobilization. 37 pts received R-BEAM and 16 received BEAM prior to ASCT. Actuarial rate for DFS was estimated from the day of SCT using the Kaplan-Meier method. Results: The group was predominantly men, 73% and 78%, with a median age of 57 years for both the R-BEAM and BEAM group. With a median follow up of 15.7 months, 13/37 (32%) and 11/16 (64%) pts who received R-BEAM and BEAM respectively developed disease progression after ASCT. The 2-yr actuarial disease-free survivals (figure1) were 60% and 21% for the R-BEAM and BEAM arm respectively (p=0.006). Conclusion: In this study, the outcome of pts who received R-BEAM compares favorably to those who receive BEAM alone with significant improvement in disease-free survival. Thus, incorporating target immunotherapy into standard conditioning regimen may have altered the natural history of the disease for pts undergoing ASCT for relapsed/refractory B-NHL. Disease Free survival Disease Free survival

Successful Peripheral Haematopoitic Autologous Stem Cells Transplants After More Than 5 Days of without Cryopreservation In Non Hodgkin Lymphoma: Asian Scenario

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4447-4447
Author(s):  
Sandeep Jasuja ◽  
Hemant Malhota ◽  
Neetu Kukar(Jasuja) ◽  
Dinesh Gautam ◽  
Shrikant Sharma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Developing Countries ◽  
Stem Cell ◽  
Median Time ◽  
Eligible Patient ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Abstract 4447 Background: Methods to simplify the stem cell transplantation procedure are the need of the hour in developing countries due to constraints of affordability and the large number of eligible patient for transplantation. Unprocessed leukapheresed material is useful to restore hemopoiesis after high dose chemotherapy and, in addition to being significantly less expensive, it also avoids the toxicity of cryopreservation (DMSO). Method: Over a period of 18 months (January 2009 to June 2010) in a hospital setting, we prospectively performed auto transplants in 5 relapsed/resistant non-Hodgkin's lymphoma patients using non-cryopreserved (stored for 5–8 days at 4°C) and un-manipulated peripheral blood stem cells mobilized by GCSF (10mg/kg/day) and GMCSF (5mg/kg/day) using a 5–7 day conditioning regimen. Viability of stem cells was checked daily by trypen blue and the cell were reinfused cells when viability comes down to less then 80% (minimum 5 days) or on day 8 which ever was earlier. The median collection of CD34+ stem cells was 2.8 × 106/cu mm (range 2–4.8 × 10 6/cumm) Result: The median time to achieve > 0.5 × 109/l granulocytes was 14 days. The median time to achieve > 20 × 109/l platelets was 16 days. CR was achieved in 4 cases. A very good partial response was achieved in 1 case. The 100-day mortality was zero. One patient, who was not in CR, died from relapse of the lymphoma, 9 months post transplant. The overall median post-transplant survival for other patients has not been reached. The approximate cost of the each graft was US$6,000. Conclusion: From this small series, we conclude that a simplified method to autograft patients avoiding purging procedures and cryopreservation of the cells is feasible. This technique helps avoid toxicity of DMSO and significantly decreases the cost of autologous hematopoietic stem cell transplant, perhaps in the world, an important issue in developing countries. Disclosures: No relevant conflicts of interest to declare.

Final analysis of the phase II, randomized, double-blind, placebo-controlled trial of single dose velafermin (CG53135–05) for the prevention of oral mucositis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6537-6537 ◽  
Author(s):  
M. W. Schuster ◽  
E. Anaissie ◽  
D. Hurd ◽  
W. Bensinger ◽  
J. Mason ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Dose ◽  
Phase Ii ◽  
Oral Mucositis ◽  
Conditioning Regimen ◽  
Study Drug ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Grade 3

6537 Background: Oral mucositis (OM) is a commonly occurring side effect of high-dose chemotherapy (HDCT) in patients (pts) undergoing autologous hematopoietic stem cell transplant (AHSCT). Velafermin, recombinant human fibroblast growth factor 20, is being investigated for prevention of OM. Velafermin promotes epithelial and mesenchymal cell proliferation in vitro and in vivo. Methods: A phase II trial was conducted to evaluate safety, efficacy, and pharmacokinetics (PK) of velafermin. Inclusion criteria: pts undergoing HDCT and AHSCT with or without total body irradiation (TBI) were enrolled. Velafermin at 0.03, 0.1, or 0.2 mg/kg or placebo was administered as single dose IV at 24h after stem cell infusion. Safety and PK were assessed. Pts were scored daily for presence of OM using the WHO grading scale. The primary endpoint was the incidence of Grade 3/4 OM. Results: A total of 212 pts were randomized to either placebo (n=51) or velafermin at 0.03 (n=50), 0.1 (n=56), or 0.2 (n=55) mg/kg (intent-to-treat or ITT sample). 206 pts (97%) received study drug or placebo. Pt diagnoses included multiple myeloma (57%), non-Hodgkin’s (25%), or Hodgkin’s (11%) lymphoma and 13 pts (6%) received TBI as part of the conditioning regimen. The Grade 3/4 OM incidence rates (%) in the placebo or velafermin arms (0.03, 0.1, and 0.2 mg/kg) were 37, 18, 38, and 36, respectively. The primary analysis of dose dependent reduction of severe OM was not statistically significant (p = 0.549). However, velafermin at 0.03 mg/kg did reduce the incidence of Grade 3/4 OM when compared to placebo alone (p = 0.031). Duration of Grade 3/4 OM was reduced significantly in the 0.03 mg/kg when every pt was evaluated or in the 0.1 mg/kg dose when only pts with Grade 3/4 OM were included in the analysis (p = 0.037 and 0.014, respectively). A total of 5 related SAEs (3 in 0.1 mg/kg, 1 in 0.03 mg/kg, and 1 in placebo cohort) occurred within 4hr of study drug infusion. All symptoms were transient. Conclusion: Single dose velafermin at 0.03mg/kg is may be active in reducing CT induced severe OM in AHSCT pts. Safety profile supports continuing study to define the optimal dose for prevention of severe OM. A new Phase II study will be conducted to confirm velafermin activity at 0.03mg/kg dose. [Table: see text]

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