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

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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Colony-Forming Unit Cell (CFU-C) Assays in Myelodysplastic Syndrome

Blood ◽

10.1182/blood.v126.23.2874.2874 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2874-2874

Author(s):

Bing Li ◽

Jinqin Liu ◽

Shiqiang Qu ◽

Robert Peter Gale ◽

Ruixian Xing ◽

...

Keyword(s):

Overall Survival ◽

Scoring System ◽

Conflicts Of Interest ◽

Unit Cell ◽

International Prognostic Scoring System ◽

Hematopoietic Stem ◽

Colony Forming Unit ◽

Significant Difference

Abstract Introduction: The myelodysplastic syndromes (MDS) are a group of clonal diseases derived from hematopoietic stem cells (HSC). Colony-forming unit cell (CFU-C) assay is an effective method to study the number and the function of HSC in vitro. In this study, we focus on the characteristics and the prognostic value of CFU-C in patients with MDS. Patients and Method: CFU-C assays were performed according to the protocol of MethoCultTM H4435 Enriched (STEMCELL Technologies). A colony was defined as an aggregate of >40 cells. Clusters consisted of 4 to 40 cells. 560 consecutive newly-diagnosed, untreated subjects with MDS diagnosed from March, 2001 to April, 2013 were studied. All subjects were reclassified according to the 2008 WHO criteria. 535 subjects with evaluable cytogenetics were classified using the International Prognostic Scoring System (IPSS) and the revised International Prognostic Scoring System (IPSS-R) criteria. Follow-up data were available for 470£¨84%£©subjects. Median follow-up of survivors was 26 months (range, 1-170) months. Subjects receiving an allotransplants were censored in survival analyses. Erythroid and myeloid colonies were isolated from each subject with one cytogenetic abnormality such as del(5/5q-) or +8. Cytogenetic abnormalities of each colony were analyzed by fluorescence in situ hybridization (FISH). SPSS 17.0 software was used to make statistical analysis. Results: Frequencies of burst-forming units-erythroid (BFU-E), colony forming unit-erythroid (CFU-E) and colony forming unit-granulocytes/macrophages (CFU-G/M) were significantly lower than normals (P<0.05) (Table 1). Subjects classified as lower risk in IPSS and IPSS-R had significantly higher numbers of BFU-E and CFU-E (P<0.05) but similar numbers CFU-G/M and clusters-G/M compared with higher risk subjects (Table 2). In 11 subjects with del(-5/5q-) or +8 identified by G- and/or R-banding, both normal and abnormal CFU-Cs were identified in 8 subjects studied by FISH. A high ratio of cluster- to CFU-G/M (>0.6) was associated with poor-risk cytogenetics (Table 2) and with worse overall survival in univariable (Figure 1, P=0.001) and multivariable analyses (HR 1.748, [1.01-3.0]; P=0.046) after adjusting for IPSS. Conclusions: These data suggest abnormalities of proliferation and differentiation of erythroid and myeloid precursor cells in vitro parallel the ineffective hematopoiesis typical of MDS and may be useful in predicting outcomes of patients with MDS. Table 1. CFU-C in MDS subtypes N BFU-E CFU-E CFU-G/M N Ratio of cluster- to CFU-G/M RA 21 8 (0-44) 40 (0-134) 14 (0-127)1 6 0.25 (0.40-1.00) RT 4 18 (4-55) 75 (60-90)1 30 (18-70)1 2 2 RARS 27 12 (0-33) 35 (1-140) 12 (0-70)1 10 0.45 (0.17-0.80) RCMD 275 10 (0-80) 33 (0-178) 14 (0-100) 126 0.35 (0-0.83) RAEB1 112 10 (0-258) 32 (0-312) 14 (0-89) 53 0.47 (0-1.00) RAEB2 103 9 (0-46) 25 (0-120) 13 (0-72) 42 0.37 (0-1.00) MDS-U 15 4 (0-58) 25 (0-161) 10 (0-43) 3 2 Del(5q) 3 2 (2-4) 15 (0-20) 5 (5-41)1 1 2 1No significant difference compared with normals. 2Too few cases to analyze. Table 2. Associations between CFU-C and clinical and laboratory variables N BFU-E P CFU-E P CFU-G/M P Number Ratio of cluster- to CFU-GM P IPSS 0.064 0.006 0.361 0.089 Low 30 13 (0-44) 60 (0-169) 19 (0-45) 10 0.44 (0.24-0.70) Int-1 361 10 (0-258) 33 (0-312) 14 (0-127) 150 0.33 (0-1.00) Int-2 115 9 (0-61) 30 (0-137) 14 (0-72) 52 0.45 (0-1.00) High 29 7 (0-34) 21 (0-93) 12 (0-67) 12 0.44 (0-1.00) IPSS-R 0.003 0.003 0.125 0.209 Very low 7 16 (9-25) 30 (15-120) 18 (5-33) 2 0.29 (0.10-0.49) Low 130 14 (0-80) 42 (0-178) 17 (0-70) 48 0.31 (0-0.77) Intermediate 173 10 (0-66) 34 (0-161) 13 (0-127) 81 0.37 (0-1.00) High 139 9 (0-259) 29 (0-312) 11 (0-89) 51 0.33 (0-1.00) Very high 86 8 (0-61) 25 (0-137) 14 (0-91) 42 0.47 (0-1.00) Cytogenetics (IPSS) 0.867 0.055 0.290 0.007 Good 327 10 (0-258) 36 (0-312) 15 (0-89) 133 0.33 (0-1.00) Intermediate 133 10 (0-69) 30 (0-162) 12 (0-127) 63 0.45 (0-1.00) Poor 75 10 (0-61) 25 (0-137) 14 (0-91) 28 0.42 (0-1.00) Cytogenetics (IPSS-R) 0.990 0.090 0.676 0.022 Very good 7 11 (4-20) 48 (1-110) 14 (8-28) 2 0.49 (0.43-0.56) Good 324 10 (0-258) 35 (0-312) 15 (0-89) 132 0.33 (0-1.00) Intermediate 129 10 (0-69) 30 (0-162) 12 (0-127) 62 0.45 (0-1.00) Poor 27 10 (0-61) 35 (0-137) 16 (0-48) 8 0.36 (0.15-1.00) Very poor 48 11 (0-42) 22 (0-120) 14 (0-91) 20 0.53 (0-1.00) Figure 1. Overall survival in subjects with cluster- to CFU-G/M ratios ¡Ü or > 60%. Figure 1. Overall survival in subjects with cluster- to CFU-G/M ratios ¡Ü or > 60%. Disclosures No relevant conflicts of interest to declare.

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A Comparison Study Between Allogeneic and Autologous Hematopoietic Stem Cell Transplant for High-Risk Peripheral T-Cell Lymphomas (PTCL)

Blood ◽

10.1182/blood.v128.22.5845.5845 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5845-5845 ◽

Cited By ~ 2

Author(s):

Haiwen Huang ◽

Qiangli Wang ◽

Zhengming Jin ◽

XiaoWen Tang ◽

Huiying Qiu ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Term Survival ◽

Hematopoietic Stem ◽

Significant Difference

Abstract Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (13-55) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 with ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 with angioimmunoblastic T-cell lymphoma (AITL). Twenty-one (21/60) received allo-HSCT and thirty-nine patients (39/60) received auto-HSCT. Before receiving transplantation, 40/60 patients were in complete remission (CR), 2/60 patients were partial remission (PR) and 18/60 patients were not remission (NR). In the 40 CR patients before transplant, 10 patients received allo-HSCT and 30 patients received auto-HSCT. In the 20 PR/NR patients before transplant, 11 patients received allo-HSCT and 9 patients received auto-HSCT. After a median follow-up of 39 (range 1-96) months, the K-M analysis showed that the 5-year PFS for auto-HSCT and allo-HSCT were 61% and 60% (P = 0.724). The 5-year OS for auto-HSCT and allo-HSCT were 62% and 61% (P = 0.724). There were no statistically significant differences between the auto-HSCT and allo-HSCT. And the cumulative TRM of allo-HSCT and auto-HSCT were 16.5% and 0 (P=0.250) within 5-years after transplantation. At the end of the last follow-up, 7 patients relapsed in auto-HSCT group and 2 patients relapsed in allo-HSCT group, the 5-year cumulative recurrence rates of auto-HSCT and allo-HSCT transplantation were 37.2% and 10.1% (P=0.298), respectively. Conclusion: There was no significant difference in the long-term survival between auto-HSCT and allo-HSCT for high risk PTCL patients. The effect of allo-HSCT may be better for NR patients. Disclosures No relevant conflicts of interest to declare.

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The Platelet Millionaire: A Rare Cause of Thrombocytosis in an Adolescent

Blood ◽

10.1182/blood-2019-129278 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5391-5391

Author(s):

Ritika Walia ◽

Theresa Sepulveda ◽

Sharon Wretzel ◽

Philip H Brandt

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

Primary Care Physicians ◽

Conflicts Of Interest ◽

Abdominal Ultrasound ◽

Cell Transplant ◽

Peripheral Smear ◽

Hematopoietic Stem ◽

Marrow Fibrosis

Objectives: Primary myelofibrosis is rare in pediatrics, often manifesting as persistent idiopathic thrombocytosis.Transitions from pediatric to adult medical care can be complicated by workup requiring invasive procedures. J.M., an 18-year-old healthy male, presented for excessive gingival bleeding after wisdom tooth extraction. Workup revealed persistent thrombocytosis to 1,165K, prompting a referral to hematology-oncology. A peripheral smear was notable for many platelets but normal RBC morphology. He had splenomegaly on abdominal ultrasound and a decreased von-Willebrand's activity to antigen ratio, suggesting acquired vWD. A bone marrow biopsy was advised; however, J.M. became lost to follow up for over 9 months owing to self-reported anxiety about the procedure. He remained asymptomatic in this interim until he re-presented to clinic for easy bruising, with no other evidence of bleeding at the time. The biopsy was pursued, revealing hypercellular marrow for age with left shifted granulocytic and erythroid maturation, abnormal megakaryocytes, and 3% blasts. This was consistent with primary early myelofibrosis (PMF), positive for MF-1, CALR, and TP53 mutations and negative for JAK2 and BCR-ABL. He was transitioned to adult hematology, maintained on baby aspirin, and referred for potential allogeneic hematopoietic stem cell transplant (HSCT). PMF is characterized by marrow fibrosis due to secretion of fibroblast growth factor by clonally proliferative megakaryocytes. It is a disease of adulthood, with 67 years being the median age at diagnosis. Only 100 cases have been reported in children, most of which are secondary to AML, ALL or other malignancies.1 Most patients present with complications of extramedullary hematopoiesis or bleeding.2 Diagnosis is suggested by a leukoerythroblastic picture on peripheral smear and confirmed with a bone marrow biopsy "dry tap" revealing marrow fibrosis.3 Prognosis in pediatric PMF is difficult to predict but outcomes tend to be worse;4 TP53 mutation is rare and based on limited adult studies may portend a poorer prognosis.5 Our young patient with this rare mutation was therefore referred for HSCT evaluation. Further complicating this case was J.M.'s anxiety, which delayed definitive diagnosis by biopsy. He only agreed to it when, at the med-peds clinic, the concept of local pain management was discussed. Anticipation of upcoming procedures by primary care physicians and close follow-up is especially important for patients transitioning from pediatric to adult providers. 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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Hematopoietic Cell Transplant Co-Morbidity Index (HCTCI) and Multiple Myeloma (MM) Survival After Autologous Hematopoietic Cell Transplantation (AHCT)

Blood ◽

10.1182/blood.v120.21.4217.4217 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4217-4217

Author(s):

Anuj Mahindra ◽

Ayman A Saad ◽

Mei-Jie Zhang ◽

Xiaobo Zhong ◽

Angela Dispenzieri ◽

...

Keyword(s):

Dose Reduction ◽

Cox Regression ◽

Conflicts Of Interest ◽

Risk Groups ◽

Hematopoietic Cell ◽

High Dose ◽

Cell Transplant ◽

Co Morbidity ◽

Significant Difference ◽

The Impact

Abstract Abstract 4217 Background: AHCT improves survival (OS) in newly diagnosed MM patients (pts) in large randomized trials. These trials have limited eligibility to younger, healthier pts. Selection of older pts and those with co-morbid illness for AHCT is problematic. HCT-CI, originally developed as predictor of post-allogeneic transplant outcomes, maybe valuable in stratifying risk of transplant related mortality (TRM) risk and OS in the AHCT setting. We investigated the relative impact of HCT CI along with other patient and MM related variables on outcomes after AHCT in a large cohort of transplant recipients. Methods: Outcomes of 1156 MM pts receiving AHCT after high dose Melphalan (MEL) between 2007 and 2010 reported to the CIBMTR (Center for International Blood and Marrow Transplant Research) were analyzed. HCTCI scores and individual comorbidities were prospectively reported at time of AHCT. Median follow up of survivors was 26 month. The impact of HCTCI and other potential prognostic factors including Karnofsky performance status (KPS) on OS were studied in multivariate Cox regression models. Results: HCTCI score was 0, 1, 2, 3, >3 in 42%, 18%, 13%, 13% and 14% respectively. Most common co-morbidities included pulmonary, diabetes, obesity, psychiatric, cardiac, renal and prior solid tumor. Using consolidated HCTCI scores, patients were stratified initially into 3 risk groups – HCTCI 0 (42%) vs. HCTCI 1–2 (32%) vs. HCTCI >2 (26%). Males and Caucasians were more likely to have greater HCTCI score. Higher HCTCI was associated with lower KPS <90 (33% in HCTCI 0 cohort vs. 50% in HCTCI >2). HCTCI score >2 was associated with MEL dose reduction to 140 mg/m2 (22% vs. 10% in score 0 cohort). Cytogenetic risk and MM related factors were not correlated with HCTCI. TRM at 12 month was 2%, 2%, and 3% for 3 risk groups. With extremely few TRM events, multivariate analysis did not suggest an impact of HCTCI. OS was 95%, 92%, 92% at 1 year and 87%, 81%, 80% at 2 year, respectively. OS was inferior for HCTCI >2 cohort (RR of death 1.48, p=0.02) and HCTCI cohort 1–2 (RR 1.37, p=0.04) compared with HCTCI 0 cohort. There was no significant difference in OS between HCTCI >2 vs. HCTCI 1–2 (p=0.64). Therefore the latter 2 groups were combined as the HCTCI >0 cohort [N=667] and compared with HCTCI=0 [N=489] in multivariate models. HCTCI >0 predicted inferior OS (RR of death= 1.41, p=0.01). Other significant predictors of inferior survival were KPS <90 (RR of death 1.61, p<0.01), IgA subtype (RR 1.64, p<0.01), >1 pretransplant regimen (RR 1.47, p<0.01), resistant MM at AHCT (RR 1.78, p<0.01). Major cause of death in both groups was progressive MM. Conclusion: In clinical practice, higher HCTCI score was associated with MEL dose reduction. Mortality after AHCT is predominantly related to MM progression/relapse with low incidence of TRM. Higher HCTCI scores were independently associated with inferior OS. KPS remains an important tool for risk stratification. Disclosures: No relevant conflicts of interest to declare.

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Effect of Immune Modulation for Peripheral T-Cell Lymphoma in Response to Relapse after Allogeneic Hematopoietic Stem Cell Transplant: A Study of 63 Patients By the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

Blood ◽

10.1182/blood.v124.21.3963.3963 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3963-3963

Author(s):

Anne-Claire Mamez ◽

Vincent Levy ◽

Patrice Chevallier ◽

Didier Blaise ◽

Stephane Vigouroux ◽

...

Keyword(s):

Overall Survival ◽

Immunosuppressive Therapy ◽

Immune Modulation ◽

Hematopoietic Stem Cell Transplant ◽

Cell Transplant ◽

French Society ◽

Hematopoietic Stem ◽

Cell Therapies ◽

Combination Treatments

Abstract Introduction: Peripheral T-cell lymphomas (PTCL) are heterogeneous diseases, lightly sensitive to chemotherapy, with an adverse outcome and a 5-year survival rate of about 30%. Allogeneic hematopoietic stem cell transplant (allo-SCT) can lead to durable remission even for patients (pts) who show poor response to chemotherapy. Several observations argue for a Graft Versus Lymphoma (GVL) effect in PTCL. However, allo-SCT is not consensually recommended, at least in first line therapy. The aim of the current study is to highlight GVL effect in PTCL. To do so, we evaluated the benefits of immune modulation on disease control (donor lymphocyte infusions (DLI) and immunosuppressive therapy tapering) with analysis of outcome in pts who relapsed after allo-SCT. Patient selection and methods: Between 1988 and 2012, 373 pts received an allo-SCT for treatment of PTCL. 80 pts in relapse after allo-SCT were identified in 27 SFGM-TC(French Society of Bone Marrow Transplantation and Cell Therapies) transplant centers. Exhaustive data were collected for 63 pts. Median age at transplant was 45 years; 67% were male. The main histopathologic subtypes were T-nos (20, 32%), primary cutaneous TCL (13, 21%) and anaplastic large TCL (11, 17%). Others were angioimmunoblastic TCL (8), T/NK lymphomas (5), HTLV1 lymphomas (5) and EIATL (1). At transplant, 38% were in complete remission (CR), 43% in partial remission (PR) and 19% had progressive disease. Median number of previous lines of treatment was 2 and 25% of the pts had previously received an autologous SCT. Conditioning regimen was myeloablative for 23 pts and non-myeloablative for 40. At relapse, pts were treated with either non-immunologic-based strategy (chemotherapy, radiotherapy) or immune modulation (DLI and/or discontinuation of immunosuppressive therapy), or both (Figure 1). We analyzed their outcomes according to the treatment they received at relapse. Results: Relapse occurred at a median time of 204 days after transplant (interquartile range: 49-190 days); seventeen pts had a localized cutaneous relapse (7 Mycosis fungoides, 2 angioimmunoblastic TCL, 3 T-nos, 3 anaplastic TCL and 2 NK/TCL). Among the 14 pts (22%) who received DLI (DLI alone: 5, DLI + radiation and/or chemotherapy: 9), 9 obtained a response (7CR, 2 PR) and 2 had a stable disease (SD) status (overall response rate: 78%). Six of these 14 pts remained alive at last follow up. Median overall survival (OS) of these 14 pts was 23.6 months. Among the 49 pts who did not receive DLI, immunosuppressive therapy was tapered or stopped for 23. Sustained CR after tapering immunosuppressive drugs was observed in2 pts along with extensive chronic graft versus host disease (cGVHD). In the non-DLI group, 30 out of 49 pts received a radio/chemotherapy treatment with a response rate of 50% and a 1-year survival rate of 25% after relapse. Among the 13/49 pts who experienced a response in this group, six developed a cGVHD after relapse. Median OS of these 49 pts was 3.6 months. Median follow up was 40 months for the whole population. Conclusion: DLI alone or in association with other therapies, when possible, seems to be an efficient salvage option. This study suggests the benefit of DLI in cases of post transplant relapse for PTCL and supports the existence of a GVL effect in these diseases. These findings could potentially lead to the set up of a proactive immune modulation strategy after transplant for pts with high-risk disease. However, the short time frame from transplant to relapse currently observed, might limit the feasibility of this therapeutic option. Figure 1: Combination treatments at relapse and response: Figure 1:. Combination treatments at relapse and response: Figure 2: Overall survival in non- DLI group (n=49) Figure 2:. Overall survival in non- DLI group (n=49) Figure 3: Overall survival in DLI group (n=14): Figure 3:. Overall survival in DLI group (n=14): Disclosures No relevant conflicts of interest to declare.

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Race as a Factor in Donor Selection and Survival of Children with Hematologic Malignancies Undergoing Hematopoietic Stem Cell Transplant in Florida

10.22541/au.161800122.22940406/v1 ◽

2021 ◽

Author(s):

Biljana Horn ◽

Deepak Chellapandian ◽

Nikhil Lamba ◽

Gauri Sunkersett ◽

Jorge GalvezSilva ◽

...

Keyword(s):

Hematologic Malignancies ◽

Unrelated Donor ◽

Cell Transplant ◽

Hla Matching ◽

Hematopoietic Cell Transplant ◽

Hematopoietic Stem ◽

Significant Difference ◽

Related Donor ◽

The Impact ◽

To Receive

Background Previous studies have explored post-hematopoietic cell transplant (HCT) outcomes by race in adults; however, pediatric data addressing this topic are scarce. Procedure This retrospective registry study included 238 White (W) and 57 Black (B) children with hematologic malignancies (HM) receiving first allogeneic HCT between 2010 and 2019 in one of five Florida pediatric HCT centers. Results We found no differences between W and B children by transplant characteristics, other than donor type. There was a significant difference in use of HLA-mismatched donors (HLA-MMD) (53% W, 71% B, p=0.01). When comparing HLA-MMD use to fully HLA-matched donors, B had RR of 1.47 [95% CI 0.7-3] of receiving a mismatched unrelated donor (MMUD), RR of 2.34 [95% CI 1.2-4.4] of receiving a mismatched related donor (MMRD), and a RR of 1.9 [95% CI 0.99-3.6] of receiving a mismatched cord blood donor (MMCBD) HCT, respectively. There was no significant difference in the incidence of aGVHD (48% W, 35% B), p=0.1 or cGVHD (19% W 28% B, p=0.1), or primary cause of death. Overall 24-month survival was 61% [95% CI 54-68%] for W, and 60% [95% CI 38-68] for B children, log-rank p=0.72. While HLA matching improved survival in W children, the number of B children receiving HLA-matched HCT was too small to identify the impact of HLA matching on survival. Conclusions In this contemporary cohort of children with HM we found that B children were more likely to receive HLA-MMD transplants, but this did not adversely affect survival or GVHD rates.

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Complex Karyotype Predicts Outcome Better Than Monosomal Karyotype In Patients with MDS/Secondary Acute Leukemia Treated with Allogeneic Hematopoietic Stem Cell Transplantation (HSCT): a Retrospective Survey on Behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Blood ◽

10.1182/blood.v116.21.578.578 ◽

2010 ◽

Vol 116 (21) ◽

pp. 578-578 ◽

Cited By ~ 2

Author(s):

Angelique .M. Brands-Nijenhuis ◽

Michel van Gelder ◽

Theo M. de Witte ◽

Johannes Schetelig ◽

Anja van Biezen ◽

...

Keyword(s):

Overall Survival ◽

Acute Leukemia ◽

Conflicts Of Interest ◽

Chromosome 7 ◽

Complex Karyotype ◽

Hematopoietic Stem ◽

Allogeneic Hsct ◽

Significant Difference ◽

Monosomal Karyotype ◽

Better Than

Abstract Abstract 578 Introduction Monosomal Karyotype (MK) has been shown to be associated with a very poor prognosis in AML patients. Last year at ASH, we presented data from the EBMT on patients diagnosed with MDS and chromosome 7 abnormalities, showing that MK predicts better than complex karyotype (CK) for a dismal outcome after allogeneic HSCT (abstract #293). We now performed a retrospective analysis on data from the registry in the complete cohort of patients with MDS and secondary AL (sAL) to determine the effect of MK on outcome after allogeneic HSCT. Methods A total of 1689 patients from 172 centres in 23 countries with diagnosis MDS or secondary acute leukemia (sAL) with known cytogenetic abnormalities (karyotype only) at diagnosis or later in the disease course were assessed. 1437 were included in the analysis; 226 were excluded because of insufficient data. Kaplan-Meier survival curves were used and log rank test to determine statistical significance. Results 1041 patients were diagnosed with MDS and 396 with sAL. Median follow up for sAL patients was 7.5 months (range 0–253) and MDS 8.0 months (range 0–276). 201 patients fulfilled criteria for MK and 279 patients for complex karyotype (CK). MK outcome was worse than no MK: overall survival 32 months versus 97 months (p=0.002). CK outcome was worse than no CK: overall survival 26 months versus 100 months (p<0.0001). No difference in outcome between MK and CK existed: overall survival of 32 months and 26 months respectively (p= 0.274). There was considerable overlap between MK and CK (i.e. patients fulfilling criteria both for MK and CK). To see how we could further differentiate, we analyzed three subgroups: MK but not CK (43 patients; MK+CK−), no MK but CK (98 patients; MK−CK+) and MK and CK (150 patients; MK+CK+). The survival of patients in each of these groups was compared with the group having no MK and no CK (n=1050). Overall survival was not different for patients with MK+CK− (median 13 vs 19 months, p=0.983), but for patients with MK-CK+ or MK+CK+ a significant difference in survival was observed with a median of 8 months (p=0.008) and 7 months (p< 0.0001) respectively. MK−CK+ and MK+CK+ did not differ statistically (p=0.42) from each other. See figure. These results differ from the results presented at ASH last year. Since this cohort consists of patients with and without chromosome 7 abnormalities, we suspect that presence of this specific chromosomal aberration is the main reason for the observed difference. Multivariate analysis will be performed the coming months. Conclusion These results indicate that CK is a better predictor for poor outcome than MK after allogeneic HSCT in this cohort of MDS and sAL patients with and without chromosome 7 abnormalities. Disclosures: No relevant conflicts of interest to declare.

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Outcome after Relapse of Childhood Acute Myeloid Leukemia: The St. Jude Experience.

Blood ◽

10.1182/blood.v106.11.273.273 ◽

2005 ◽

Vol 106 (11) ◽

pp. 273-273

Author(s):

Jeffrey Rubnitz ◽

Bassem Razzouk ◽

Shelly Lensing ◽

Stanley Pounds ◽

Ching-Hon Pui ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Significant Difference ◽

First Remission ◽

Acute Myeloid

Abstract We reviewed the records of 408 patients who were less than 21 years old at the time of diagnosis of acute myeloid leukemia (excluding patients with Down syndrome or acute promyelocytic leukemia) treated on five consecutive institution protocols from 1980–2002 to investigate prognostic factors for attainment of second complete remission (CR2) and overall survival (OS) after first relapse. Of the 320 (78%) patients who achieved CR, 158 patients suffered hematologic relapses at a median of 11.9 months (range, 2.9–119.9 months) from the time of diagnosis. Forty-one patients relapsed on therapy and 117 relapsed after the completion of all planned therapy. For patients who relapsed off therapy, 38 were diagnosed with relapse because of symptoms suggestive of recurrent leukemia and 78 were diagnosed at the time of a routine follow up (information not available for one patient). After relapse, 20 patients received palliative care, 82 received chemotherapy alone, 36 received chemotherapy followed by hematopoietic stem cell transplant (SCT), and 20 proceeded directly to SCT. Eighty-five (54%) patients attained CR2. In univariate analyses, factors associated with the achievement of CR2 include initial therapy (chemotherapy alone, 56%; autologous SCT, 71%; allogeneic SCT, 20%; p=0.008) and time from the diagnosis of AML to relapse (≤ 1 year, 44%; > 1 year, 65%; p=0.010). Logistic regression analysis demonstrated that patients with male gender (odds ratio [OR], 2.46; 95% confidence interval [CI], 1.14–5.28; p=0.021) and greater time from diagnosis to relapse (OR, 1.05; CI, 1.01–1.09; p=0.016) were more likely to achieve CR2, whereas patients with M7 morphology (OR, 0.11; CI, 0.01–1.04; p=0.054) and allogeneic SCT in first remission (OR, 0.17; CI, 0.03–0.85; p=0.031) were less likely to achieve CR2. At the time of last follow up, 19 patients were alive, 115 died of progressive disease, and 24 died of regimen-related toxicity. The 2-year OS estimate ± SE for the entire cohort of 158 patients was 15.8% ± 2.8%. For patients who relapsed off therapy, there was no significant difference in outcome between those whose relapse was diagnosed at the time of a routine follow up and those diagnosed because of symptoms. Cox proportional-hazards regression modeling indicated that M7 morphology (hazard ratio [HR], 3.06; CI, 1.44–6.51; p=0.004) and allogeneic SCT in first remission (HR, 2.17; CI, 1.22–3.87; p=0.008) were associated with significantly worse OS after relapse. In fact, there were no survivors in these two groups of patients. In contrast, age 1–10 years (HR, 0.53; CI, 0.36–0.77; p=0.001), M2 morphology (HR, 0.57; CI, 0.39–0.85; p=0.006), allogeneic SCT after relapse (HR, 0.34; CI, 0.22–0.53; p<0.001), and greater time from diagnosis to relapse (HR, 0.97; CI, 0.95–0.99; p=0.003) had significantly favorable effects on OS. However, outcome was poor even among patients who underwent allogeneic SCT after relapse (2-year OS, 34.5% ± 6.1%) and among patients who relapsed greater than one year from diagnosis (2-year OS, 19.2% ± 4.3%), suggesting that novel therapies are warranted for all patients with relapsed AML.

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Utility of Plerixafor In Addition to Chemotherapy and G-CSF Mobilization Regimens

Blood ◽

10.1182/blood.v116.21.4443.4443 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4443-4443

Author(s):

Farrukh Awan ◽

David Deremer ◽

Elaine Mebel ◽

Samith Thomas Kochuparambil ◽

Anand P. Jillella

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Peripheral Blood ◽

Conflicts Of Interest ◽

Chemotherapeutic Agents ◽

Phase Iii ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Cd34 Cells ◽

Significant Difference

Abstract Abstract 4443 Introduction: Various chemotherapeutic agents particularly cyclophosphamide (CY) are utilized in combination with growth factors in an attempt to increase the number of stem cells available for collection in the peripheral blood. Plerixafor (P) is a reversible antagonist of CXCR4 and interrupts its interaction with SDF-1. This results in a rapid release of hematopoietic stem cells from the marrow to the circulation. Recent pivotal phase III trial data has established the efficacy of P in combination with G-CSF (G) in patients who had failed prior attempts at stem cell collection. However, there is limited data about the utility of plerixafor in patients who are being mobilized with chemotherapy and G. Method: In this single institution study of uniformly treated patients we describe our experience with the use of P as a salvage option in patients who fail to optimally mobilize CD34+ cells (>5 × 106 CD34+ cells/kg). Patients received CY (3-4 g/m2) followed by GCSF (10 mcg/kg) from day 1 to day 10. Thirteen patients (6 NHL, 4 MM, 2 Hodgkin lymphoma, 1 Ewings sarcoma) received salvage P from 2008–2010. Their outcomes were compared with 10 matched, historic controls mobilized with (CY n=8; CY + etoposide n=1; CY + topotecan n=1) plus G-CSF (10mcg/kg/d) identified from our institutional database. Data was collected on mobilization and transplant outcomes and analyzed utilizing SPSS version 13.0. Patients receiving P were closely matched to historic controls (CY+G). Result: Both groups were similar with regards to age, gender, disease type, prior therapies and performance status (p>0.05 for all). Patients in the P arm received a median of 2.5 doses (range 1–8). The mean CD34+ count was 21.5cells/ul in the P arm and 32.5 cells/ul in the CY+G arm (p=0.2). Similarly, no significant difference was observed in the average number of apheresis sessions in the P vs. CY+G arms (4.2 vs. 4.4, p=0.8) or the total number of CD34+ stem cells collected (4.0×106/kg vs. 3.9×106/kg, p=0.9). However, 7 out of the 13 patients who received P did have an increase of >10 CD34+ cells/ul in their peripheral blood. Utilizing a cut-off of 5×106 CD34+/kg, 3 (23%) patients in the P arm and 3 (30%) patients in the CY+G arm had a successful harvest. Three NHL patients required >4 doses of P, but all eventually collected >2 × 106 CD34+ cells/kg. Neutrophil and platelet engraftment dynamics were similar in both groups of patients. Median time to neutrophil engraftment was 10 days for both groups, p=0.8, and to platelet engraftment was 22 days vs. 20.5 days, p=0.1, respectively for P vs. CY+G. Conclusion: Our limited single-center retrospective case-controlled outcomes data, suggests that when compared with CY+G, the addition of P as a salvage agent does not significantly improve mobilization outcomes. Further evaluation is needed to combine P with CY+G in terms of optimal timing and potentially dosing of chemotherapy agents utilized. We suggest that the combination P+G would provide better potential outcomes such as improved collection and less hospitalization and reduce the use of chemo-mobilization prior to an Autologous Hematopoietic Stem Cell Transplant. Disclosures: No relevant conflicts of interest to declare.

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