The Utility Of Monitoring Chimerism: More Predictive For Nonablative Regimens?

Abstract Introduction Treatment related mortality and overall survival of allogeneic stem cell transplants have improved over the past 30 years but disease relapse remains the primary cause of death. New tools are sought to detect a window for early intervention. Chimerism studies are one tool that may allow clinicians to recognize impending graft failure or disease recurrence. Use of chimerism data varies in terms of frequency of monitoring and decision-making based on results. In this single-center study we evaluated the use and utility of chimerism studies in patients undergoing ablative and nonablative stem cell transplants for hematologic malignancies. Methods Following IRB approval, a retrospective chart review of 133 patients undergoing allogeneic stem cell transplant for leukemia or MDS at our institution during the period from 2007-2012 was performed. Of this group, 90 had chimerism studies performed using the Promega PowerPlex 16 System. Full donor chimerism (FDC) was defined as donor hematopoeisis of greater than or equal to 95% in both CD3 and CD33 lineages. Mixed donor chimerism (MDC) was defined as donor hematopoeisis of less than 95%. Patients with FDC at all assessments were categorized as complete chimerism (CC). Patients with MDC initially that improved on subsequent evaluation were categorized as improving chimerism (IC). Patients with FDC that devolved into stable MDC or worsening MDC were categorized as worsening chimerism (WC). Fifteen patients were unclassifiable due to incomplete data and were excluded. A univariate statistical analysis was performed on the remaining 75 patients and overall survival (OS), disease specific survival (DSS), and relapse free survival (RFS) determined. A sub-analysis using Chi-Square and Fisher's Exact Test was performed on individuals in the nonablative cohort with WC or IC to investigate whether there were higher rates of intervention in the IC group. Results Demographic data for the ablative cohort and nonablative cohort, and among patients with CC, IC and WC were similar. There was no statistically significant difference in OSS or DSS between patients with CC, IC and WC. There was a statistically significant hazard ratio favoring both CC and IC versus WC in terms of RFS in the nonablative cohort and in the combined cohort but this was not seen in the ablative cohort (Table 1). Within the nonablative group, there was not a higher rate of withdrawal of immunosuppression (p=0.98), donor lymphocyte infusion (p=0.43), or additional disease-specific therapy (p=0.43) in the IC versus the WC group to explain the improving chimerism, suggesting that interventions based on chimerism results are either too late or are inadequate. Discussion This study suggests that chimerism studies have utility in the setting of nonablative transplant where WC predicts worse RFS. Despite this additional prognostic information, the window for early intervention is narrow and we were unable to demonstrate that improvements in chimerism studies were related to clinician initiated interventions in this small study. The risk of developing GVHD must be weighed in deciding to withdraw immunosuppression or administer DLI given the relatively low success rate of changing MDC into FDC. Finally, despite our institutions' recommendation of monitoring chimerism studies serially, 32% of the charts we reviewed had not had these studies performed. Given the complexity and heterogeneity of patients with hematological malignancies, more evaluation of chimerism studies is needed to fully establish or discredit the potential utility of this test. Disclosures: No relevant conflicts of interest to declare.

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Donor-Specific Isoagglutinin Clearance in ABO Mismatched Stem Cell Transplant Recipients: How Long Should It Normally Take?

Blood ◽

10.1182/blood-2018-99-115075 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1260-1260 ◽

Cited By ~ 1

Author(s):

John Chinawaeze Aneke ◽

Nayana Sondi ◽

Santhosh Thyagu ◽

Christine M. Cserti-Gazdewich ◽

Jacob Pendergrast

Keyword(s):

Stem Cell ◽

Plasma Cells ◽

Conflicts Of Interest ◽

Pure Red Cell Aplasia ◽

Cell Transplant ◽

Post Transplant ◽

Expected Time ◽

Significant Difference ◽

Cell Transplants ◽

Stem Cell Transplants

Abstract Introduction: In patients undergoing ABO-incompatible stem cell transplants, recipient isoagglutinins with specificity for donor antigens are expected to slowly become undetectable during the post-transplant period, presumably secondary to the loss of recipient plasma cells via either conditioning chemotherapy or graft-versus-host-disease. Conversely, the persistence or return of these anti-donor isoagglutinins may induce hemolytic anemia or pure red cell aplasia, and may even signify disease relapse. In order to define the expected time to clearance of these donor isoagglutinins at our institution, a retrospective study was performed Methods: The transfusion records of all major-side or bidirectionally ABO-incompatible stem cell transplants performed at an academic cancer hospital between May 2009 and July 2018 were reviewed. Patients without detectable anti-donor isoagglutinins at time of transplant were excluded. Isoagglutinin clearance was defined as non-reactivity of patient plasma against donor-type reverse grouping cells occurring during the post-transplant period; relapse was defined as a 2+ or stronger reaction after one or more non-reactive results Results: A total of 280 patients were included in analysis, of which 44 were native group A, 42 group B and 194 group O. Average age was 52 (±13) years and 130 (46%) were female. Compatibility samples were sent to the UHN blood bank during the post-transplant period for a median of 156 days (IQR 74-370 days). During this time period, donor-targeting/host-derived isoagglutinin clearance was documented in 192 (69%) patients at a median of 48 days (IQR 23-116.5) post-transplant. Of these, 52 (30%) experienced a subsequent return of reactivity at a median 98 days post-transplant (IQR 54-216). Amongst the 128 patients with at least 28 days of post-transplant monitoring and no return of previously cleared isoagglutinins, the median time to clearance was 60 days (IQR 26.5 - 127.5 days). There was no statistically significant difference in time to isoagglutinin clearance between those with and without a subsequent return of reactivity, and time to durable clearance did not correlate with patient age, sex or native ABO group. Conclusions: Amongst patients undergoing major-side or bidirectionally ABO incompatible stem cell transplants, the majority will have cleared their donor-specific isoagglutinins within 120 days of stem cell infusion, although this does not guarantee against later return of reactivity. Thus, the persistence of donor-specific isoagglutinins beyond 120 days post-transplant, or the subsequent return of previously cleared isoagglutinins, may be considered abnormal results which warrant notification of the clinical team by the hospital transfusion service. Disclosures No relevant conflicts of interest to declare.

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Hematopoietic Stem cell transplant in National Oncology Cancer Institute of Panama. Ten Years of Experience

Blood ◽

10.1182/blood.v118.21.4524.4524 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4524-4524

Author(s):

Jose Luis Franceschi Diaz

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Cell Transplants ◽

Stem Cell Transplants ◽

Hematopoietic Stem Cell Transplants

Abstract Abstract 4524 Panama has a population of 3.5 million inhabitants. Between 2,000 and 2,010 there were 123 hematopoietic stem cell transplants at the INSTITUTO NACIONAL DE ONCOLOGIA (ION). Even though, there are two other specialized centers doing the same procedures that we do, the ION has the greatest experience in the whole country. The objective of this document is to show you our experience and the results of a third level cancer center in an undeveloped country with limited financial resources however with pathologies and diseases that request bone marrow transplant programs installed and developed. The bone marrow transplant program (BMT) of ION initiated at the beginning of 2,000 and since then, it has been doing approximately 10–12 HSCT annually. Material and Methods: We did a review of the data during this first decade and the most important epidemiological and statistics data are presented next. Results: There were 85 autologous and 28 allogeneic hematopoietic stem cell transplants. In the allo group there were 4 reduced intensity included. In every single auto hematopoietic stem cell transplants the source of progenitor stem cells were peripheral blood and in the case of allo, hematopoietic stem cell transplants the source was the bone marrow in 18 cases and the peripheral blood in 20 cases. The mean of CD34 + progenitor cell infused was 3.23×106 (range 2.12–9.93). The peripheral blood progenitor cells were cryopreserved in liquid nitrogen until −136° celsius degrees using controlled rate temperature computerized freezers. The cells were protected from damages during the cryopreservation with cryoprotectant, in this case dimethil sulphoxide 10% was used. The age range was from 17 to 65 years old with a mean of 39 years old with a median of 40 years old. There were 66 males and 57 females. The main indication for Hematopoietic stem cell transplant was Hodgkin disease in 20 cases; follicular lymphoma in 13 cases; large cell lymphoma in 12; chronic myeloid leukemia in 21; adult acute lymphoblastic leukemia 17; adult acute myeloid leukemia in 10; multiple myeloma in 22 (2 pts. were transplanted twice upfront); severe aplastic anemia in 1; myelodisplastic syndrome in 1; lymphoblastic lymphoma in 4, and gray zone lymphoma in 1. The day 100, mortality rate for all patients was 16.3 per 100 with a range between 5–21.1 per 100 according to different diseases and types of transplants. The overall survival for all patients has a median of 59 months but when it is analyzed according to the transplant type with log rank test, there was no significative difference in the overall survival (p = 0.063). However, when all the population is grouped in categories according to diseases in Hodgkin disease; lymphomas; multiple myeloma and leukemias there is a clear difference in plot overall survival, in all four groups statistically significative with the most desfavorably outcome in the leukemia group. Indeed, if all the group is divided in two groups leukemia vs. others, there would be a clear difference in overall survival with a median overall survival of 12 months in the leukemia group that hasn’t been reached in the other group after more than 5 years of follow up (log rank p = 0.014). In all the groups there have been 55 deaths; 20 in the allo hematopoietic stem cell transplant group; and in these patients the main causes were relapse in 12 patients; graft vs. host disease in 3; infection in 4, organ toxicity in 1. There were 35 deaths in were in the auto hematopoietic stem cell transplant group, and in these patients the main group of deaths were relapse in 25 patients; infections in 3; organ toxicity in 2. Acute graft vs host disease (aGVHD). in allo hematopoietic stem cell transplant did affected desfavorably the outcome as we can see in the overall survival plot in comparison to patients without aGVHD (log rank test, p = 0.014). Chronic graft versus host disease (cGVHD) also affected desfavorably the outcome in allo hematopoietic stem cell transplant in comparison to patients with cGVHD (log rank p = 0.002). Conclusion: these results show that a BMT program can be performed in an undeveloped country with efficiency and efficacy. Disclosures: No relevant conflicts of interest to declare.

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Dose Intensive Induction Chemotherapy Does Not Decrease Tumor Contamination of Autograft or Improve Survival for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplant.

Blood ◽

10.1182/blood.v106.11.2932.2932 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2932-2932

Author(s):

Farzana A. Sayani ◽

Nizar J. Bahlis ◽

Peter Faris ◽

Mary Lynn Savoie ◽

Ahsan Chaudhry ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Small Sample ◽

Cell Transplant ◽

Intensive Chemotherapy ◽

Kaplan Meier ◽

Significant Difference ◽

Time To Relapse

Abstract Multiple dose intensive chemotherapy regimens have been used for induction/mobilization of stem cells for autologous stem cell transplantation (ASCT) in multiple myeloma. However, the exact role and regimens of such dose intensive chemotherapy has not been clearly defined. We therefore did a retrospective study to determine if dose intensive cyclophosphamide (Cyclo) 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in improved relapse rate and survival compared to standard mobilization with only Cyclo 2 g/m2. Between January 1998 and March 2004, a consecutive series of 57 newly diagnosed multiple myeloma patients receiving DICEP (38) or Cyclo (19) for in-vivo purging/mobilization were analyzed. Both groups were similar in regards to age and sex. There were no significant differences in IPI score, Durie-Salmon stage, B2 microglobulin, calcium, creatinine and albumin levels between treatment groups. Outcomes included time to relapse and time to death. Median follow up time was 799 days. Kaplan-Meier plots for time to relapse showed no significant difference (p=0.0992). Median relapse time in the DICEP group was 905 days (95% CI 580–1604) compared to 1112 days (95% CI 742-infinity) in the Cyclo group. Kaplan-Meier plots for overall survival showed no significant difference between both groups (p=0.8664). The median survival times have not yet been reached in either group and are not reported. Analysis revealed no discernable confounding risk factors. Effects of treatment on outcomes were not altered after adjusting for IPI score and Durie-Salmon staging using the stratified log-rank test. Small sample size and short duration of followup are potential limiting factors for this study, however, preliminary analysis of a larger sample of 91 multiple myeloma patients receiving either DICEP or a less intense induction/mobilization regimen, also revealed no significant difference in disease free or overall survival. Monoclonal plasma cell contamination of stem cell products was not significantly different between both groups (DICEP 42.9%, Cyclo 56.3%, p=0.5573). This study therefore suggests that the very intense DICEP induction/mobilization regimen results in no significant difference in survival outcomes. The more intense regimen does not significantly decrease tumor contamination of autograft stem cells. Overall, our experience suggests that novel induction therapies such as bortezomib, lenolidomide etc. should be pursued in preference to any further study of high dose cytotoxic chemotherapy induction. Figure Figure

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Low Day 30 Total Donor Chimerism After Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation Is Associated with Poorer Overall Survival In Myeloid but Not Lymphoid Disorders

Blood ◽

10.1182/blood.v116.21.1325.1325 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1325-1325

Author(s):

John Koreth ◽

Haesook T Kim ◽

Vincent T. Ho ◽

Corey Cutler ◽

Philippe Armand ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

T Cell ◽

Donor Cell ◽

Reduced Intensity Conditioning ◽

Hematopoietic Stem ◽

Donor Chimerism ◽

High Risk Disease ◽

Disease Specific ◽

Reduced Intensity

Abstract Abstract 1325 While some studies associated an increased relapse rate and poorer progression-free survival with lower donor T-cell chimerism after reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT); early total donor cell chimerism, despite its use as a clinical trial endpoint, is not established as a predictor of survival. In part this may reflect its non-uniform impact across hematologic malignancies. Clarifying the survival impact of early donor chimerism could help identify patients who may benefit from additional interventions; and also define its value as a disease-specific endpoint. We undertook a retrospective analysis of adult patients undergoing 8/8 HLA-matched RIC HSCT from 2002–2008 with available day 30 total donor cell chimerism (range, 20–50 days; PB or marrow). All received fludarabine/busulfan-based conditioning with sirolimus- and/or tacrolimus-based GVHD prophylaxis. Umbilical cord blood transplants; ex-/in-vivo T-cell depletion (e.g. ATG); or malignant relapse/progression at or prior to day 30 chimerism were excluded. 414 patients with a median age of 58 years (range, 41–69) and median follow-up among survivors of 34 months (range, 6–80) were analyzed. Patient characteristics: 211 myeloid (116 AML, 63 MDS, 20 CML, 12 MPD); 203 lymphoid (70 NHL, 66 CLL, 39 HD, 21 MM, 6 ALL); 343 (83%) with high-risk disease; 265 (64%) were males; 404 (98%) received peripheral blood stem cells; 234 (57%) had matched-unrelated donors; and 132 (32%) had prior transplants. Day 30 total donor cell chimerism was <50% in 32 patients (8%); 50–89% in 99 patients (24%); and ≥90% in 283 patients (68%). Factors predictive of lower day 30 chimerism were high-risk disease (p<0.01), no prior transplant (p<0.01), male sex (p=0.02) and myeloid diagnosis (p=0.03). In univariable analyses patients with lower day 30 chimerism had worse 3-year progression-free and overall survival (PFS, OS) (p<0.0001; p=0.003). The cumulative incidence of chronic GVHD correlated with the degree of day 30 chimerism (p=0.049). Stratified by diagnosis, lower day 30 chimerism was associated with poorer 3-year PFS and OS in myeloid (p<0.0001; p<0.001) but not in lymphoid disorders (p=0.09; p=0.66) (Figure). For both myeloid and lymphoid disorders, lower day 30 chimerism was associated with increased incidence of relapse (p<0.0001; p=0.02) but not of non-relapse mortality (p=0.24; p=0.41). In multivariable Cox-models, day 30 chimerism <50% was associated with lower PFS and OS (HR 3.13, 95% CI 2.04–5, p<0.0001; HR 2.27, 95% CI 1.41–3.57, p<0.001). For myeloid disorders, day 30 chimerism <50% was associated with poorer PFS and OS (HR 6.25, 95% CI 3.23–11.11, p<0.0001; HR 3.33, 95% CI 1.82–6.25, p=0.0001). For lymphoid disorders, day 30 chimerism <50% was associated with poorer PFS (HR 2.13, 95% CI 1.09–4.17, p=0.03) but not OS (HR 1.44, 95% CI 0.65–3.23, p=0.36), that may reflect in-part longer survival after lymphoid compared to myeloid relapse. However, there may also be disease-specific differences. For instance, low day 30 chimerism was highly associated with poorer PFS and OS in AML/MDS (HR 4.54, 95% CI 2.13–10, p<0.0001; HR 3.33, 95% CI 1.67–10, p=0.001); had a trend of PFS impairment in CLL/NHL (HR 2.17, 95% CI 0.97–5, p=0.06); but had no impact in HD or myeloma. In conclusion day 30 total donor chimerism <50% is an independent predictor of poor survival after T-cell replete RIC HSCT. Routine assessment of day 30 chimerism in myeloid disorders helps identify a patient subset with significantly worse RIC HSCT outcomes, who may be candidates for trials of additional therapies to improve survival. Conversely, it may be a less relevant RIC HSCT endpoint in lymphoid disorders, where its survival impact appears more limited.Figure:Day 30 Total Donor Chimerism and RIC HSCT Overall Survival: by DiagnosisFigure:. Day 30 Total Donor Chimerism and RIC HSCT Overall Survival: by Diagnosis Disclosures: No relevant conflicts of interest to declare.

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Impact of Rapid Lymphocyte and Monocyte Recovery on Overall Survival Post-Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine/Melphalan Conditioning

Blood ◽

10.1182/blood.v118.21.3040.3040 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3040-3040

Author(s):

Lori DeCook ◽

Mary Thoma ◽

Tanya Huneke ◽

Nicole Johnson ◽

Robert Wiegand ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Acute Leukemia ◽

Hematopoietic Stem Cell ◽

Conflicts Of Interest ◽

Positive Impact ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Absolute Lymphocyte Counts ◽

Complete Blood Counts

Abstract Abstract 3040 We have previously shown that both lymphocyte and monocyte recovery are strongly associated with improved survival post-myeloablative allogeneic hematopoietic stem cell transplant for acute leukemia (Thoma et al, Biology of Blood and Marrow Transplantation, in press). We hypothesized that rapid lymphocyte and monocyte recovery would have a similarly positive impact on overall survival in reduced intensity conditioning (RIC) HSCT with fludarabine/melphalan. To test our hypothesis, we analyzed 118 consecutive patients who underwent allogeneic HSCT with fludarabine/melphalan conditioning for AML (n=49) and MDS/MPN (n=38), ALL (n=7) and other lymphoid malignancies (n=24) at our institution from 2001–2010. The absolute lymphocyte counts and monocyte counts (ALC and AMC, respectively) derived from routine complete blood counts were determined longitudinally at days +15, +30, +60, +100 and correlated with clinical outcomes. At the day +30 time point, both ALC and AMC > 0.3 × 10(9) cells/L were strongly associated with improved survival (OS 29.6 months vs. 5.4 months, p=0.006 and 25.3 months vs. 5.1 months, p=0.01 respectively), a pattern that continued through the day +100 evaluation. Multivariate analysis including age, CD34+ cell dose, unrelated vs. related HSCT, presence of aGVHD, remission status, and longitudinal hematologic parameters revealed that day +100 ALC (RR 0.21, 95% CI 0.07–0.66, p= 0.0096) and day +100 AMC (RR 0.41, 95% CI 0.2–0.9, p=0.047) were the only independent predictors of survival in the model. Pairwise correlations showed moderate negative associations between aGVHD and day +60 and day +100 ALC and AMC. To further explore whether any inherent patterns in the timing of lymphocyte and monocyte recovery had prognostic value post-HSCT, we performed unsupervised hierarchical clustering on the longitudinal hematopoietic parameters studied in this cohort and identified four clusters of patients, clusters A-D. Patient clusters A and C both demonstrated improved ALC and AMC recovery at the day +60 and day +100 time points and had significantly improved OS compared with clusters B and D (not reached for A and C vs. 54.9 and 22.3 months, respectively, p<0.001). No patient in cluster D had a day +100 AMC > 0.3 × 10(9) cells/L, and these patients experienced more acute GVHD (p=0.006) and relapse (8 of 14 patients, p=0.002) compared with clusters A, B, and C (p=0.002). 29 patients who were unable to be clustered with this algorithm, predominantly due to early toxic deaths, had a median survival of 6 months. Consistent with previous observations in our myeloablative cohort, both lymphocyte and monocyte recovery are predictive of overall survival post-RIC HSCT. However, compared to the myeloablative cohort, monocyte recovery in this series appears slightly less strongly associated with survival. Our results also extend the observation of improved survival of ALC and AMC recovery post-HSCT to diseases beyond acute leukemia. Disclosures: No relevant conflicts of interest to declare.

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Increasing Rates of Fluoroquinolone Resistance in Escherichia coli Blood and Urinary Isolates in Stem Cell Transplant and Hematologic Malignancy Populations

Pathogens and Immunity ◽

10.20411/pai.v1i2.115 ◽

2016 ◽

Vol 1 (2) ◽

pp. 234 ◽

Cited By ~ 11

Author(s):

Christopher G. Hauck ◽

Pearlie P. Chong ◽

Melissa B. Miller ◽

Katarzyna Jamieson ◽

Jason P. Fine ◽

...

Keyword(s):

Escherichia Coli ◽

Stem Cell ◽

Hematologic Malignancy ◽

Hematologic Malignancies ◽

Fluoroquinolone Resistance ◽

Cell Transplant ◽

Cell Transplants ◽

Stem Cell Transplants ◽

Febrile Episodes ◽

Urinary Isolates

Fluoroquinolone (FQ) antibiotics have been shown to reduce mortality and the number of febrile episodes when used as prophylaxis during neutropenia. Prior studies suggest that prophylaxis may result in increasing rates of FQ resistance. Fluoroquinolone non-susceptibility trends in Escherichia coli isolated from blood and urine cultures were evaluated over a 16-year period during which prophylaxis was initiated in patients with hematologic malignancies and stem cell transplants. Non-susceptibility rates increased after the introduction of prophylaxis, with yearly non-susceptibility rates rising from 30%–33% to 40%–88% in blood isolates. The high rates of non-susceptibility now observed raise concerns about the continued efficacy of FQ prophylaxis. This concern exists particularly in those patients undergoing stem cell transplants where the total FQ non-susceptibility rates over the study period were 82.3%. Further evaluation of the effect of FQ prophylaxis on antibiotic resistance and its efficacy in the setting of increased rates of resistance is warranted.

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581. Risks versus Benefits of Metronidazole Use for the Prevention of Acute GVHD in Allogeneic Stem Cell Transplant Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.775 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S355-S356

Author(s):

Mary T Young ◽

Marguerite Monogue ◽

Hetalkumari Patel

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Adverse Drug Events ◽

Cell Transplant ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Post Transplant ◽

Clostridioides Difficile ◽

Cell Transplants

Abstract Background Currently, acute graft versus host disease (aGVHD) prophylaxis in hematopoietic stem cell transplants (HSCT) varies amongst different institutions. There is a lack of data supporting the use of metronidazole for aGVHD prophylaxis in HSCT. To further investigate if metronidazole has an effect on aGVHD, allogeneic HSCT recipients will be examined to determine if metronidazole post-transplantation decreases the incidence of aGVHD and the risks of adverse drug events (ADE) associated with this practice. Methods This retrospective study included 120 adult patients who received an allogeneic HSCT between January 1, 2010 to December 31, 2013. The primary endpoint is the incidence of aGVHD, defined as within 100 days post-transplant. Secondary endpoints include the rate of metronidazole discontinuation due to intolerance, frequency of metronidazole-related adverse effects, incidence of Clostridioides difficile infection, mortality, and overall survival. Results One hundred six patients met the inclusion criteria. The majority of patients received metronidazole (88 vs. 18). Less patients in the metronidazole arm developed aGHVD (51.1% vs 61.1%, p=0.44). In the subcategories of liver, skin, and gastrointestinal aGHVD, patients who received metronidazole developed less gastrointestinal aGVHD (26.1% vs 50.0%, p=0.045). Gastrointestinal ADEs were the most common metronidazole-related ADEs (19.3%, Table 1). There were no significant differences in the incidence of C. difficile infection, mortality, and overall survival between the two arms (Table 2). Table 1. Adverse Drug Events and Discontinuation of Therapy Table 2. Additional Secondary Outcomes Conclusion Despite a reduction in gastrointestinal aGVHD in the metronidazole arm, approximately one in four patients experienced an ADE to the medication, likely due to the prolonged use of the medication (33 days). The utilization of post-transplant cyclophosphamide for GVHD prophylaxis likely eliminates the need for metronidazole; however our findings suggest a benefit in preventing gastrointestinal aGVHD with metronidazole; albeit, caution is warranted given the high incidence of ADE associated with prolonged use. Disclosures All Authors: No reported disclosures

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Effective Management of Patients with Leukemic Transformation of Myelofibrosis.

Blood ◽

10.1182/blood.v114.22.4967.4967 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4967-4967

Author(s):

Shyamala C. Navada ◽

John Mascarenhas ◽

Vesna Najfeld ◽

Ronald Hoffman

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Stem Cell ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Single Agent ◽

Unrelated Donor ◽

Cell Transplant ◽

Leukemic Transformation ◽

Transfusion Requirements

Abstract 4967 Introduction Myelofibrosis (MF) is a clonal stem cell Philadelphia chromosome negative myeloproliferative neoplasm (MPN) characterized by progressive cytopenias, massive splenomegaly, early satiety, and a hypercatabolic state manifested by fevers, fatigue, and weight loss. Approximately 10-20% of MF patients will transform to acute myeloid leukemia (AML) over a 10-year period with a median overall survival at time of transformation of 2.6 months (Mesa 2005). In a multivariate analysis, peripheral blood blast count > 3% and/or a platelet count < 100 × 109/L at time of diagnosis of MF were independent risk factors for leukemic transformation (LT) (Huang 2008). Standard induction chemotherapy improved survival to 3.9-5 months (Mesa 2005, Tam 2008). Survival was decreased due to a high relapse rate and treatment-related mortality. Patients who received an allogeneic stem cell transplant early in the disease course had superior survival. We describe the outcome of ten consecutive patients with MF-LT at our institution. Patients and Methods A retrospective chart review was performed to evaluate patients with MF-LT, including clinical characteristics, therapies administered, and survival outcomes. Between the years of 2007 and 2009, ten MF-LT patients were identified in our institution. The median age was 66 (range 45-77) with 60 percent male and 40 percent female patients. Thirty percent (3/10) of patients were JAK2 V617F positive. Seven patients were cytogenetically abnormal and three had a normal karyotype. Chromosomal abnormalities included +1q (2 pts), +8 (2 pts), -7 (2 pts), inv 3 (1 pt), and t(6;9) (1 pt). Fifty percent of patients had a post-essential thrombocythemia related MF, while 30 percent had an MDS/MF overlap syndrome. Time to LT ranged from 3 months to 12 years with a median of 12 months. In three cases, there was discordance between bone marrow blasts by immunohistochemical staining and peripheral blood manual count. Six patients were treated with decitabine at 20 mg/m2 for 5 days (for two to ten cycles), and four received reduced intensity conditioning allogeneic stem cell transplantation (RIC-ASCT). Patients were eligible for RIC-ASCT if they were under 70 years of age, had no significant comorbidities, and had either an HLA compatible sibling or an unrelated donor with at most one mismatched allele. Results The median survival from diagnosis of LT with the use of decitabine has not yet been reached but exceeds 7.5 months in this patient population. Two out of six patients treated with decitabine died 6 and 8 months after LT. The remaining four patients are still alive at 6, 7, 9, and 36 months after LT and are actively receiving therapy. Four out of six patients who received decitabine had subjective improvement in fatigue as well as decrease in splenomegaly. Three out of six patients had a decrease in transfusion requirements. The four patients who underwent RIC-ASCT are all alive after a median follow-up of 16.5 months with no evidence of leukemia in the bone marrow. Conclusions These results demonstrate that single-agent decitabine for those who are not eligible for transplant or RIC-ASCT for eligible patients, leads to a significant improvement in overall survival. Further investigation using these therapeutic modalities is warranted given the aggressive nature of this disease. Furthermore, the noted discordance between bone marrow and peripheral blood blast percentage most likely reflects leukemic cell production originating at sites of extramedullary hematopoiesis. Disclosures No relevant conflicts of interest to declare.

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Validation of the EBMT Risk Score for Patients with Hematologic Malignancies Receiving Allogeneic Hematopoietic Stem Cell Transplant in a Transplant Center in Colombia over 20 Years

Blood ◽

10.1182/blood.v126.23.5542.5542 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5542-5542

Author(s):

Virginia Abello ◽

Carmen Rosales ◽

Manuel Rosales ◽

Javier Figueroa ◽

Iris Cordoba ◽

...

Keyword(s):

Overall Survival ◽

Latin America ◽

Risk Score ◽

Conflicts Of Interest ◽

Risk Groups ◽

Hematologic Malignancies ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Significant Difference

Abstract INTRODUCCION EMBT the risk score has been validated in several studies in different types of diseases and modalities of transplantation. The conditions of the patients and the resources available in Latin America are different from those of European centers, so we consider important to validate this scale in our own patients. METHODS EBMT risk scale was validated in 965 of 1176 (750 autologous, allogeneic 426) transplanted from 1993 to 2014; that had all the information available and were not lost to follow up. Kaplan-Meier survival curves and log-rank test (p <0.05) were used to estimate the one (OS1) and three (OS3) probabilities of overall survival according to risk groups. RESULTS The mean age was 39.8 (SD 15.5). The median follow-up was 363 days (range: 179-1096) for the whole group. Most frequent diagnoses were Non-hodgkins lymphoma (314: 26.7%) and multiple myeloma (262: 22.22%). 96.3% transplants were performed using peripheral blood stem cells. Most donors were identical siblings; only 19.5% (n = 79) were transplanted before 2004. 81.9% of transplanted patients had 2-4 points on EBMT risk score. Upon analysis it became clear that at 1 and 3 years, two groups were defined: Low (0-3 points) and high (4-7), with a significant difference in overall survival for AML (1 year: p = <0.00; 3 years: p = <0.00) and ALL (1 year: p = 0.04; 3 years: p = 0.01). In NHL 4 risk groups remain significantly different in regards to 1 and 3 years overall survival (1 year: p = 0.04; 3 years: p = 0.02). In patients with diagnosis of MDS EBMT was predictive of survival only significant at one year (p = 0.01). The EBMT score did to delineate risk groups patients with MM, LH, ASMO, or CML in this group. CONCLUSION EBMT score was validated in patients with hematologic malignancies transplanted in a center in Colombia, to our knowledge this is the first validation of this risk score in Latin America. Disclosures No relevant conflicts of interest to declare.

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