Treatment Related Mortality of AML Pediatric Patients in a Single Center in Saudi Arabia

Abstract Abstract 4291 Despite minimal changes in therapeutic approach, the outcome of acute myeloid leukemia (AML) in pediatric patients has improved significantly in the past two decades. Supportive care measures may have contributed to this success by reducing treatment related mortality (TRM) and thereby improving the overall survival (OS) of patients. Yet their impact on outcome remained unknown and masked under protocol effect. To assess the impact of supportive care measures on outcome, we undertook a retrospective review of all pediatric patients diagnosed with AML between 1986 and 2011and treated in our institution, the Princess Norah Oncology Center, King Abdulaziz Medical City, Jeddah. A total of 87 patients were reviewed. Of these, two patients whose parents refused treatment and one lost to follow-up were excluded. A total of 84 patients were qualified for the study. These patients were treated with two different protocols based on treatment eras. Patients diagnosed between 1986 and 1995 (era 1) were treated following AML-BFM-78 protocol while patients diagnosed between 1996 and 2011 (era 2) were treated following the MRC AML10. The cumulative TRM incidence was 76% in era1 compared to 11.5% in era 2 (P = 0.0001). This resulted in an improved 5-year OS from 10.5% in era 1 to 56% in era 2 (P = 0.007). The protocols used in both eras were different and may have improved OS. Significant difference in TRM however, suggests that other factors contributed to the improved OS. To gain further insight of the contributing factors, patients who received only MRC AML10 protocol (in era2) were partitioned into two sub-eras based on supportive care measures introduced sequentially in our institution as follows: 1996 to 2002 (era 2a) and 2003 to 2011 (era 2b).The cumulative TRM incidence was 48.6% in era 2a and 4.7% in era 2b (P = 0.001). This also resulted in an improved OS from 33.3% in era 2a to 56.2% in era 2b despite using the same protocol (P = 0.007). Our findings highlight the importance of supportive care as a significant factor in outcome of children. Comparing protocols per se masks the importance of supportive care measures in impacting outcome. We suggest devising a standardized scoring system to evaluate center-specific supportive care measures to quantify the impact of supportive care on TRM and survival outcomes while simultaneously allowing us to distinguish the effect of supportive care from that of protocol and other factors such as ethnicity. Disclosures: No relevant conflicts of interest to declare.

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Declining Rates of Treatment-Related Mortality in Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Given “Intensive” Induction Regimens: A Report From the Southwest Oncology Group (SWOG) and MD Anderson Cancer Center (MDA)

Blood ◽

10.1182/blood.v120.21.129.129 ◽

2012 ◽

Vol 120 (21) ◽

pp. 129-129 ◽

Cited By ~ 3

Author(s):

Megan Othus ◽

Hagop M. Kantarjian ◽

Stephen Petersdorf ◽

Farhad Ravandi ◽

Jorge E. Cortes ◽

...

Keyword(s):

Supportive Care ◽

Conflicts Of Interest ◽

Performance Status ◽

Cancer Center ◽

Cell Transplant ◽

Newly Diagnosed ◽

Secondary Aml ◽

Over Time ◽

Treatment Related Mortality ◽

Related Mortality

Abstract Abstract 129 Background Recent emphasis has been placed on administration of induction regimens less intense than standard 3+7 for patients with newly diagnosed AML. A primary goal is to reduce the presumed average treatment related mortality (TRM) rate of 10% occurring within the first 28 days after start of 3+7 or higher intensity therapies; TRM rates have been > 30% in patients who are older and/or have poor performance status (PS]. (Walter et al. JCO 2012). This practice presupposes that TRM rates with higher intensity induction regimens are static, a notion seemingly difficult to reconcile with advances in supportive care (e.g. newer anti-aspergillosis drugs) that have sharply reduced rates of non-relapse mortality after allogeneic hematopoietic cell transplant (Gooley et al. NEJM 2010). Methods We thus addressed rates of TRM from 1991–2009 in 1,409 patients given 3+7 induction regimens on SWOG protocols (cytarabine dose 100 mg/m2 daily × 7) and 1,933 patients given induction regimens containing higher cytarabine doses (at least 1.0 g/m2 daily × 4–5 days) at MDA, variably combined with idarubicin, fludarabine or other agents. Multivariate analyses were used to account for confounding factors. Results TRM rates declined both in SWOG and at MDA. However this reduction must account for the declining ages of patient given 3+7 or more intense induction (p<0.001 in both SWOG and at MDA) and their improved PS (p<0.001 SWOG and MDA);the considerably younger nature of SWOG patients during 2006–2009 reflects the switch to less intense induction regimens for many older patients; such regimens were not included in this analysis. Additionally other covariates associated with TRM (more blood blasts, lower platelets, secondary AML) by Walter et al. (JCO 2012)were unevenly distributed in the various time periods(for example no secondary AML in SWOG 2006–2009). Multivariate logistic regression was thus performed to account for the effect of age, PS, and these other covariates in the reduction in TRM. After such accounting, odds ratios (ORs) for TRM at MDA were (relative to 1995) 0.89, 0.7, and 0.36 for 1996–2000,2001–2005, and 2006–2009 respectively with the null hypothesis of no change over time rejected at p = 0.006. For SWOG, not including secondary AML as a covariate ORs were (relative to 1991– 1995) 0.75,0.78, and 0.42 for 1996–2000,2001–2005,and 2006–2009 respectively; again the hypothesis of no change with time was rejected (p = 0.037). There were no interactions between reduced TRM and age, WBC or performance status suggesting the reduction in TRM was a general phenomenon. Conclusion There has been a reduction over time in TRM after “intensive” induction possibly due to better supportive care. Although various selection biases cannot be excluded, this decline is not due to younger age or better performance status and needs to be considered when choosing AML induction therapy. Disclosures: No relevant conflicts of interest to declare.

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Increased Use of Allogeneic Transplant in CR2 Improves the Outcome for Children with Acute Myeloid Leukaemia

Blood ◽

10.1182/blood.v126.23.2521.2521 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2521-2521

Author(s):

Aditi Vedi ◽

Richard Mitchell ◽

Cecelia Oswald ◽

Glenn M Marshall ◽

Toby Trahair ◽

...

Keyword(s):

Acute Myeloid Leukaemia ◽

Supportive Care ◽

Myeloid Leukaemia ◽

De Novo ◽

Conflicts Of Interest ◽

Induction Treatment ◽

Allogeneic Transplant ◽

Significant Difference ◽

Related Mortality ◽

Acute Myeloid

Abstract Improvements in Outcome for Paediatric de novo Acute Myeloid Leukaemia Aditi Vedi1,2, Richard Mitchell1, Cecelia Oswald1, Glenn Marshall1,2, Toby Trahair1, David S Ziegler1,2 1Kids Cancer Centre, Sydney ChildrenÕs Hospital, Randwick, NSW, Australia, 2 School of Women and Children's Health, University of New South Wales, Randwick, NSW, Australia ABSTRACT The treatment for paediatric acute myeloid leukaemia (AML) has not changed significantly over the past 3 decades, yet outcomes have improved with cure rates increasing from 30% to over 50% of all newly diagnosed children over this period. This improvement in survival has been attributed to both treatment intensification and improved supportive care over the decades, although the precise impact of each remains unknown. Our group has retrospectively analysed a unique cohort of patients with de novo AML diagnosed in childhood (n=276), all treated with the same chemotherapy protocol over a 25-year period from 1986-2012. The contemporary cohort (2000-12), compared to historical cohorts (1986-99) had significantly improved overall survival (OS, 75% vs. 50%, p = 0.01), lower disease related mortality (38% vs. 19%, p = 0.02) and were significantly more likely to receive allogeneic transplant after relapse (SCT, 73% vs. 12%, p <0.0001). Allogeneic transplant post relapse was associated with a significantly improved survival across the entire cohort (OS 50% for allogeneic SCT vs. 12% for autologous or none, p<0.0001). There was no significant difference between the contemporary and historical cohorts in treatment related mortality (13% vs. 7%, p = 0.42) or relapse rates after induction (50% in older cohort vs. 40% in recent era, p=0.25), suggesting consistency of induction treatment efficacy and toxicity across the two periods. This data suggests improved survival in paediatric AML in the modern era has predominantly resulted from increased use of allogeneic SCT after relapse rather than from improved supportive care and is independent of chemotherapy intensification. Disclosures No relevant conflicts of interest to declare.

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A strategy to improve treatment-related mortality and abandonment of therapy for childhood ALL in a developing country reveals the impact of treatment delays

Pediatric Blood & Cancer ◽

10.1002/pbc.25510 ◽

2015 ◽

Vol 62 (8) ◽

pp. 1395-1402 ◽

Cited By ~ 24

Author(s):

Amaranto Suarez ◽

Martha Piña ◽

Diana X. Nichols-Vinueza ◽

John Lopera ◽

Lyda Rengifo ◽

...

Keyword(s):

Developing Country ◽

Childhood All ◽

Treatment Delays ◽

Improve Treatment ◽

The Impact ◽

Treatment Related Mortality ◽

Related Mortality

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Comorbidities Index Is Not Predictive of Treatment Related Mortality in Patients (pts) Older Than 60 Years Treated with Reduced Intensity Conditioning and Allogeneic Stem Cell Transplantation (RIC-ALLO).

Blood ◽

10.1182/blood.v114.22.1180.1180 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1180-1180

Author(s):

Luca Castagna ◽

Sabine Furst ◽

Jean El Cheikh ◽

Catherine Faucher ◽

Mohamad Mohty ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Viral Infections ◽

Conflicts Of Interest ◽

Chronic Gvhd ◽

Univariate Analysis ◽

Treatment Related Mortality ◽

Related Mortality

Abstract Abstract 1180 Poster Board I-202 Benjamin Esterni, Didier Blaise Background: Allogeneic stem cell transplantation (ALLO) is the only curative therapy for many hematological malignancies. For many of these diseases, the median age at diagnosis is around the sixth decade of life, precluding myeloablative ALLO (MAC-ALLO). RIC-ALLO is less toxic and it has been performed in elderly pts, mainly affected by acute leukemia. Finally, comorbidities index seem to predict treatment related mortality (TRM) and overall survival (OS). Patients and methods: From 2001 and 2008, 67 pts older than 60 years (median age 63 y, range 60-70) received RIC-ALLO. Diseases were: acute myeloid leukemia 45%, multiple myeloma 18%, chronic lymphocytic leukemia 12%, non-Hodgkin lymphoma 10%, myelodysplasia 6%, plasmacellular leukemia 3%, others 6%. Disease status at RIC-ALLO was: complete remission 54%, partial remission 16%, and active disease 30%. RIC consisted of fludarabine-based with thymoglobulin 64%, or low-dose TBI-based 36%. Donors were: HLAid sibling 73%, matched unrelated 21%, and cord blood 6%. Previous autologous transplant was performed in 59% of pts. The median number of CD34+ and CD3+ cells infused was 5 (range 1-9.4) and 296 (range 84-704), respectively. Karnofski score was 60-80% in 25% and 90-100% in 75%; HCT-CI was 0 in 33%, 1-2 in 33%, and more than 3 in 34%; PAM score was 8-16 in 9%, 17-33 in 65%, 24-30 in 22%, and more than 31 in 3%; EBMT score was 2 in 22%, 3 in 36%, 4 in 28%, more than 5 in 12%. Results: The median follow-up was 22 months. The 2-y OS and PFS were 66.8% (IC95 [55.5-80.4]) and 52.4% (IC95 [39.5-69.5]), respectively. Grade II-IV acute graft versus host disease (aGVHD) and chronic GVHD (cGVHD) incidence were 49% and 43%, respectively. Early infections were fever of unknown origin in 42% of pts, bacterial infection in 6 cases, pneumonia in 8, and viral infections in 14. The early infection-related mortality was null. Late infections were bacterial in 3 cases, pneumonia in 1, viral infections in 6, and candidemia in 1. Seven pts died from late infective complications. Overall, the cause of death was toxicities in 18 pts and disease progression in 6 pts. The 100-d and 1-y TRM were 6.35% (IC95 [0.278-12.4]) and 24.2% (IC95 [12.9-35.4]), respectively. In univariate analysis, HCT-CI, EBMT score, and PAM score did not influence TRM or OS. Furthermore, age (60-65 vs 66-70) was not related to TRM. Conclusions: The aim of this retrospective study was to verify if TRM was excessively high in elderly pts, affected from several haematological diseases and receiving ALLO from different donors and after different RIC. A secondary objective was to evaluate if several comorbidities index could predict TRM and OS. This heterogeneity should be regarded as a more realistic view of general population. TRM was acceptable and not different when compared to younger pts as reported in literature. Furthermore, neither comorbidities index nor age help segregate a group of pts with different TRM. Disclosures: No relevant conflicts of interest to declare.

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TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽

10.1182/blood.v114.22.4866.4866 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4866-4866

Author(s):

Luciana Correa Oliveira de Oliveira ◽

Juliana Alves Uzuelli ◽

Ana Paula Alencar de Lima Lange ◽

Barbara Amelia Aparecida Santana-Lemos ◽

Marcia Sueli Baggio ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Prognostic Factors ◽

Bone Disease ◽

Cox Regression ◽

Conflicts Of Interest ◽

Newly Diagnosed ◽

Significant Difference ◽

The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

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Re-Exposure of Cord Blood (CB) to Non-Inherited Maternal HLA Antigens (NIMA) Improves Transplant Outcome in Patients (pts) with Hematologic Malignancies and May Reduce Relapse.

Blood ◽

10.1182/blood.v114.22.661.661 ◽

2009 ◽

Vol 114 (22) ◽

pp. 661-661

Author(s):

Jon J van Rood ◽

Cladd E Stevens ◽

Jacqueline Smits ◽

Carmelita Carrier ◽

Carol Carpenter ◽

...

Keyword(s):

Conflicts Of Interest ◽

Chronic Gvhd ◽

Hla Antigens ◽

Human Leukocyte ◽

Hematologic Malignancies ◽

Hematopoietic Stem ◽

Leukocyte Antigens ◽

Grade Ii ◽

The Impact ◽

Related Mortality

Abstract Abstract 661 CB hematopoietic stem cell transplantation (CBT) can be successful even if donor and recipient are not fully matched for human leukocyte antigens (HLA). This may result, at least in part, from tolerance-inducing events during pregnancy, but this concept has not been tested to date. Hence we analyzed the impact of fetal exposure to NIMA of the HLA-A, -B antigens or -DRB1 alleles on the outcome of 1121 pts with hematologic malignancies. All pts received single CB units provided by the NYBC, for treatment of ALL (N=451), AML (N=376), CML (N=116), MDS (N=79), other (N=99); 22% were transplanted in advanced stage. Median age was 9.7 years (range: 0.1-67); 29% of recipients were >16 years. Most pts (96%) received myeloablative cytoreduction. Sixty-two pts received fully matched grafts while 1059 received units mismatched (MM) for one or two HLA antigens. Of these, 79 (7%) had a MM antigen which was identical to a donor NIMA (Example: Pt: A1, A3; CBU: A1, A2; mother-CBU: A1, A3; A3 is NIMA). NIMA match was found in 25 recipients with one HLA MM and 54 of those with two MM. The NIMA match was identified after the transplant and was not used in unit selection. In multivariate analyses, NIMA matched transplants (NMTs), showed faster neutrophil recovery (RR=1.3, p=0.043), even for grafts with cell dose <3×107 (RR=1.6, p=0.053). There was no difference in the incidence of acute (grade II-IV) or chronic GvHD. 3-year relapse risk (cumulative incidence 22%) was reduced compared to 1 or 2 HLA MM no NIMA matched transplants, especially in pts with myelogenous malignancies given units with 1 HLA MM (RR=0.2, p=0.074). Further, 3-year transplant-related mortality was reduced (RR=0.7, p=0.034), particularly in pts ≥5 years old (RR=0.5, p=0.006), as was the 3-year overall mortality (RR= 0.7, p=0.029 and RR=0.6, p=0.015, respectively). As a result, in the NMTs, treatment failure (relapse or death) was significantly lower, particularly in pts ≥5 years (RR=0.7, p=0.019) and DFS was significantly improved (figure) and was similar to that of the 0 HLA MM group. These findings are the first indication that donor exposure to NIMA can improve post-transplant survival in unrelated CBT and might reduce relapse. We propose to include the NIMA of CB units in search algorithms. Thus, for pts lacking fully HLA matched grafts, HLA MM but NIMA matched CB units could be selected preferentially, since no adverse effects were seen. This strategy of selecting HLA MM grafts with optimal outcome effectively “expands” the current CB Inventory several-fold.Patient GroupNRR(95% Cl)p value0 MM360.5(0.3–0.8)0.0051 MM / NIMA Match180.4(0.2–0.9)0.0262 MM / NIMA Match400.8(0.5–1.2)0.3091 MM / No NIMA Match229reference group2 MM / No NIMA Match4871.1(0.9–1.3)0.365 Disclosures: No relevant conflicts of interest to declare.

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Association of PML Expression with Chemotherapy-Resistance In Multiple Myeloma Cells

Blood ◽

10.1182/blood.v116.21.2959.2959 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2959-2959

Author(s):

Daisuke Ohgiya ◽

Makoto Onizuka ◽

Hiromichi Matsushita ◽

Naoya Nakamura ◽

Hiroshi Kawada ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Cellular Proliferation ◽

Conflicts Of Interest ◽

Alkylating Agents ◽

Chemotherapy Resistance ◽

Nuclear Body ◽

Rank Test ◽

Significant Difference ◽

The Impact

Abstract Abstract 2959 Background: Although several novel agents have improved the prognosis of patients with multiple myeloma (MM), it still remains an incurable disease because of the difficulty to eradicate MM cells by current therapeutic approaches. Recent studies have revealed that a subset of malignant cells, cancer stem cells, contribute to chemotherapy-resistance in cancer treatment. Promyelocytic leukemia gene product (PML), known as a tumor suppressor through a variety of cellular functions in a nuclear macromolecular structure called the PML nuclear body, has been reported to be responsible for the chemotherapy-resistance by regulating cell cycle in chronic myeloid leukemia. We therefore investigated the impact of PML expression on the cellular proliferation status of MM cells and patients' prognoses. Materials/Methods: Bone marrow clot sections from 48 patients with newly diagnosed MM from Jan 1998 to Dec 2009 before any therapy at diagnosis were obtained, and analyzed, according to appropriate procedure approved by IRB at the Tokai University School of Medicine (Kanagawa, Japan) with written informed consent. They were doubly-stained with a combination of anti-PML/anti-CD138 and anti-Ki67/anti-CD138. For evaluation of the relation between PML status and cellular proliferation, the positive rates of PML and Ki67 in CD138 positive cells were compared. For investigation of the impact of PML expression on the prognosis of MM, the patients were divided into 3 groups, according to the PML positive rates in the CD138 positive cells: negative/low (less than 25 percentile: 12 cases), intermediate (from 25 to 75 percentile: 24 cases) and high (more than 75 percentile: 12 cases). Their overall survivals were compared using log-rank test. Furthermore, the PML positive rates between before and after treatments were compared using paired t-test. Results: The median observation period of 48 cases was 915 days. The median age of the patients was 62.5 (38-76) at diagnosis. All the patients were underwent combination chemotherapies containing alkylating agents as initial therapies. Two and nine patients were underwent allogeneic and autologous stem cell transplantation during the clinical courses, respectively. The numbers of patients of international staging system (ISS) stage I, II and III were 17, 14 and 17 cases. The PML positive rates in each case ranged from 0% to 83.8%. They were not correlated with ISS stages (Spearman r = 0.083) and the Ki67 positive rates (Spearman r = -0.13). The PML positive rates in the negative/low, intermediate and the high groups were less than 22.1%, from 22.1 to 56.6% and more than 56.6%, respectively. No significant difference in overall survival was observed among the 3 groups (p>0.05). However, there were significant differences in two year survival rate when the 3 groups were compared (100%, 85.2% and 54.7%; p=0.015) (Fig. 1). In 13 patients whose bone marrow clot sections were sequentially collected, the PML positive rates after treatments were significantly higher than those at diagnosis (p=0.0042) (Fig. 2). Especially, PML positive rates in all the 3 patients from the negative/low group were progressively increased (0.3 to 82.6%, 14.1 to 100%, 19.0 to 37.5%), and 2 of them died due to disease progression. On the other hand, 2 patients whose PML positive rates decreased after treatment were alive more than 5 years without therapies. Conclusion: Our data indicated that the level of the PML expression at diagnosis was a possible prognostic factor for early course of the disease (2 years after diagnosis). Chemotherapies might induce PML expression in MM cells or select PML positive MM cells. These findings suggest that PML expression presumably reflect chemotherapy-resistance in MM cells. The molecular mechanism of the association is now under investigation. Disclosures: No relevant conflicts of interest to declare.

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Cytogenetic Evolution (CE) In Patients (pts) with Low and Intermediate Risk Myelodysplastic Syndromes (MDS) Is Associated with Poor Prognosis

Blood ◽

10.1182/blood.v116.21.2941.2941 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2941-2941

Author(s):

Liunan Li ◽

Elias Jabbour ◽

Gautam Borthakur ◽

Stefan Faderl ◽

Tapan Kadia ◽

...

Keyword(s):

Disease Progression ◽

Cytogenetic Analysis ◽

Conflicts Of Interest ◽

Myelogenous Leukemia ◽

Intermediate Risk ◽

Hematopoietic Stem ◽

Increased Risk ◽

Significant Difference ◽

The Impact ◽

Cytogenetic Evolution

Abstract Abstract 2941 Introduction: MDS is a spectrum of abnormalities in the proliferation and differentiation of hematopoietic stem cells that result in peripheral cytopenias, bone marrow dysplasia and increased risk of transformation to acute myelogenous leukemia (AML). Cytogenetic abnormalities occur in more than 50% of patients (pts) and have an impact on survival and risk of transformation to AML. CE, or acquisition of additional clonal chromosomal abnormalities, has been reported to occur in 30 to 50% of primary MDS pts. Their impact on prognosis and transformation into AML among pts with low and intermediate risk MDS is not known. In this study, we analyzed the impact of CE on prognosis in lower risk MDS. Methods: we reviewed 722 pts clinic records of low and intermediate risk MDS pts at MD Anderson Cancer Center (MDACC) from 2000–2010 and conducted a retrospective analysis of all MDS pts with at least two consecutive cytogenetic analysis (365 patients, 50.6%) and compared the cytogenetic evolution group (CE group) with the group without cytogenetic changes (no CE group). Cytogenetic analysis was performed in the Cytogenetics Laboratory at MDACC. Results: CE was detected in 200 pts (55%). Characteristics of patients with CE are: median age 65 years (23-91), IPSS int-1 79%, diploid CG 42%, excess blasts 25%. Pts with CE were more frequently female (p=0.005), and had more frequently abnormalities of chromosome 5 and 7 (p<0.001) at baseline. There were no statistically significant difference between these two groups (p>0.05) regarding age, WBC, platelet, hgb, ANC, BM blasts percent, diagnosis (RA or RAEB), and IPSS score. There were more chr.-5/-7, insufficient metaphases, and other abnormalities, but less diploid cases in CE group compared with no CE group (p<0.001). History of malignancy (p=0.001) and prior chemotherapy exposure were also associated with CE (p=0.001), but this was not as strong for radiation exposure (p=0.066). Also, more CE patients required therapy for MDS compared to no CE patients (p=0.039). Progression free survival was significantly extended in no CE patients (p=0.02). Overall survival was a longer in no CE (34.1months), compared with CE group (26.2 months), although this was not statistically significant. Conclusion: CE is more commonly observed among pts with high-risk features, and is usually associated with disease progression and resistance. Also, prior malignancy and chemotherapy exposure were associated with CE in this study. This data indicates that genomic instability has a role in disease progression in MDS. Further analysis of CE in MDS is needed. Disclosures: No relevant conflicts of interest to declare.

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Evaluation of Enteral Versus Parenteral Feeding As Nutritional Support In Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v118.21.4576.4576 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4576-4576

Author(s):

Richard Lemal ◽

Romain Guièze ◽

Cécile Moluçon-Chabrot ◽

Eric Hermet ◽

Aurélie Ravinet ◽

...

Keyword(s):

Stem Cell ◽

Median Duration ◽

Nutritional Support ◽

Conflicts Of Interest ◽

Conditioning Regimen ◽

Hematopoietic Stem ◽

Early Outcome ◽

Transfusion Requirements ◽

Significant Difference ◽

The Impact

Abstract Abstract 4576 Introduction Allo-HSCT procedure is associated with a frequent and potentially severe malnutrition which could highly participate to the transplant-related morbidity (TRM). Optimal nutritional management is still poorly known while both enteral nutrition (EN) and parenteral nutrition (PN) are effective. We proposed to retrospectively evaluate the impact of EN versus PN as nutritional support on early outcome of allo-HSCT. Patients and methods We retrospectively analyzed all the successive patients who needed a nutritional support during their first allo-HSCT in our center from January 2009 to October 2010, excepting whose who had a progressive disease at time of transplant. Datas were compared in an intent to treat analysis according the EN or PN initial nutritional support strategy. Results We analysed early outcome of 56 successive patients. Twenty of them received a myeloablative conditioning regimen and 36 a reduced intensity one. A total of 28 agreed to receive EN via a nasogastric feeding tube and the remaining 28 received PN. No significant difference in terms of age, diagnosis, disease status at transplant, conditioning regimens, stem cell source, GVHD nor antifungal secondary prophylaxis could be observed between the EN and PN groups. We found a lower median duration of fever in EN (2[0–8] vs. 5[0–17] (days); p=0.0026) and a lower need for antifungal therapy in EN group (7/28 vs. 17/28; p=0.0069), with a lower median duration of intravenous antifungal use (0 day [0–99] in EN vs. 7 days [0–93] in PN; p=0.00034) while incidence of bacteriemiae was not different. We observed a lower rate of replacement of central veinous catheter in EN group (3/28 in EN vs. 9/28 in PN; p=0.05) and a lower rate of transfer to ICU in the EN group (2/28 in EN vs. 8/28 in PN, p=0.036) but early death rate (<100 days) was the same in each group (4/28 vs. 4/28, p=NS). Median neutropenia and thrombopenia duration and median transfusion requirements were not significantly different. Fourteen patients in EN group and 18 in PN group presented a grade 3–4 oral mucositis (p=NS). Grade III-IV GVHD incidence was comparable in both groups (4/28 vs. 8/28; p=0.19). Conclusion Compared with PN, EN directly decreases the infectious risk, particularly the fungal risk, and its complications in allo-HSCT, without influencing hematopoietic toxicity nor GVHD incidence. Based on these encouraging results, we are now conducting a prospective, multicentric and randomized trial to confirm EN benefice in allo-HSCT. 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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