Hospitalization for Chemotherapy Toxicities (Chemotoxicities) during Treatment of Pediatric Hematologic Malignancies

Abstract Background: The projected 5y survival rates for pediatric hematologic malignancies exceed 85% (SEER statistics, 2017), in large part due to risk-stratified intensive multi-agent therapeutic approaches. However, these regimens result in chemotoxicity, often requiring hospitalization. However, the burden of chemotoxicity-related hospitalizations in children with hematologic malignancies remains understudied. Methods: Using an administrative claims database (Truven Marketscan ®), we describe chemotoxicity-related hospitalizations within the first 12 mo from first claim of chemotherapy in children with hematologic malignancies who were <21y at diagnosis. Eligibility included (i) incident acute lymphoblastic leukemia (ALL; ICD-10-CM code: C91), acute myeloid leukemia (AML; C92), Hodgkin lymphoma (HL; C81) or non-Hodgkin lymphoma (NHL; C83.0, C83.3, C83.5, C83.7, C84.4, C85) diagnosed between 2011 and 2018; and (ii) continued insurance coverage 30d prior to and 365d after cancer diagnosis. Chemotoxicities (identified using ICD-9 and -10 codes) were grouped into organ systems (hematologic, infectious, gastrointestinal, renal, allergic, pulmonary, central nervous system, cardiovascular and miscellaneous). A hospitalization was considered chemotoxicity-related if a toxicity diagnosis was the primary reason for admission (i.e., first billing code) or occurred in the second billing position only if the cancer diagnosis was in the primary billing position. Hospitalizations for chemotherapy administration for primary or relapsed cancer were excluded. Logistic regression was used to examine the following factors for their association with chemotoxicity-related hospitalization: age at cancer diagnosis, sex, year of diagnosis (2011-2014; 2015-2018), insurance (commercial, Medicaid) and primary cancer diagnosis. Results: We identified 897 eligible patients (ALL: n=461, AML: n=79, HL: n=202, NHL: n=155). Median age at diagnosis was 15y (range, 0-21), 52.7% were male, 54.2% were diagnosed between 2011 and 2014, and 70.2% had commercial insurance. Medicaid patients were younger than those with commercial insurance (median age at diagnosis: 12y [range, 0.9-21] vs. 17y [0-21y]), and were less likely to carry a diagnosis of ALL (46% vs. 54%, P<0.001) but more likely to have AML (15% vs. 6%, P<0.001). Over the 4,736 person-months of follow-up, 360 patients (40.1%) had 636 chemotoxicity-related hospitalizations (ALL: 56.9%, AML: 8.9%, HL: 20.9%, NHL: 13.2%); 164 (18.3%) patients had ≥1 chemotoxicity-related hospitalization. Median time to first chemotoxicity-related hospitalization from start of therapy was 37d (interquartile range, 12-78). Chemotoxicity claims included hematologic toxicities (63.6%), infections (22.7%) and gastrointestinal toxicities (6.1%); the figure shows the distribution of claims during these hospitalizations by hematologic malignancy. The average length of stay (LOS) for chemotoxicity-related hospitalization was 6.8±8.7d [5.8±7.8d (HL) to 8.6±12.6d (AML)]. Multivariable logistic regression analysis identified Medicaid insurance (vs. commercial) to be associated with lower odds of chemotoxicity-related hospitalization (odds ratio=0.68, 95% confidence interval 0.56-0.84, P<0.001). Conclusions: Over 40% of children with hematologic malignancies require chemotoxicity-related hospitalizations during the first year of treatment. These data could be used to provide guidance to patients and their families and inform healthcare policy decisions. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Fludarabine, Mitoxantrone and Rituximab (FMR) Regimen in Previously Untreated Patients with Indolent Non-Hodgkin Lymphoma: Efficacy, Safety and PET Data On 285 Patients.

Blood ◽

10.1182/blood.v120.21.2736.2736 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2736-2736

Author(s):

Pier Luigi Zinzani ◽

Cinzia Pellegrini ◽

Enrico Derenzini ◽

Alessandro Broccoli ◽

Letizia Gandolfi ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Bone Marrow Involvement ◽

Stage Ii ◽

Hematologic Toxicity ◽

Free Survival ◽

Non Hodgkin Lymphoma ◽

Significant Difference ◽

Grade 3

Abstract Abstract 2736 In this retrospective single-center study we aimed at evaluating the efficacy and safety of fludarabine, mitoxantrone and rituximab (FMR) regimen as first line therapy in untreated patients with follicular non-Hodgkin lymphoma (NHL) and indolent non-follicular NHL considering also the role of positron emission tomography (PET) after this chemo-immunotherapy induction as predictor of survival. Between January 2000 and May 2011, 285 patients with stage II-IV untreated indolent follicular (excluding grade IIIb) NHL (n=142) and indolent non-follicular (including marginal zone lymphoma, MZL [n=111] and small lymphocytic lymphoma, SLL [n=31]) NHL (n=143) were diagnosed and treated at our institution in the outpatient clinic. Median age was 63 years (range, 25–83 years) and the median time from diagnosis to study entry was 3 months (range, 1–5 months). 20 patients had stage II, 75 patients had stage III, and 190 had stage IV disease (155 patients had bone marrow involvement). Standard fludarabine (25 mg/m2 iv on days 2, 3 and 4), mitoxantrone (10 mg/m2 iv on day 2) and rituximab (375 mg/m2 iv on day 1) were given every 28 days for six cycles. Globally, after FMR regimen, the overall response rate (ORR) was 83.2%, including a 71.6% complete remission (CR) rate (204 patients) and a 11.6% partial remission (PR) rate (33 patients). According to the histology, in the follicular subset, the ORR was 81.1% with a CR rate of 69.2% while in the indolent non-follicular subset the ORR was 85.2% with a CR rate of 73.9%. In particular, in the indolent non-follicular NHL subgroup the CR rate was 80.2% in MZLs and 51.6% in SLLs, respectively. Toxicities were generally mild and mainly hematologic. Overall 88 (30.8%) patients had grade ≥3 hematologic toxicity, and 26 (9.1%) patients had non-hematologic toxicity with 3 cases of grade ≥3 (1 neurologic toxicity and 2 hepatic toxicity). In terms of secondary malignancies, only 3 (1.0%) hematologic neoplasms were reported (1 myelodisplastic syndrome after 9 months from the end of the treatment and 2 acute lymphoblastic leukemia after 8 and 11 months from the end of the treatment, respectively). Globally with a median follow up of 40 months (range, 12–144 months), at 11 years the overall survival (OS) was 78.8%, the disease-free survival (DFS) was 73.4% (with only 29 relapses), and the progression-free survival (PFS) was 71.9%. Regarding the comparison between the two subsets, follicular vs indolent non-follicular, no statistically significant differences were observed in OS, DFS and PFS curves. Furthermore, a sub-sample of 132 patients (75 follicular NHLs and 57 indolent non-follicular NHLs) had a PET evaluation before the treatment (staging) and 4 to 6 weeks after completion of the sixth cycle of chemo-immunotherapy (restaging, final PET [f-PET]). Post-induction PET-positive patients had a significantly inferior OS at 6 years: 71.4% compared with 98.4% for f-PET-negative patients (p<0.0001, Figure 1a). In terms of PFS at 6 years, there was not a statistically significant difference among f-PET-positive patients and f-PET-negative patients (Figure 1b). Figure 1a. Figure 1a. Figure 1b. Figure 1b. In conclusion, this study suggests and confirms that FMR is a very active, well tolerated (in terms of acute and long-term side effects) chemo-immunotherapy front-line treatment for follicular NHL and indolent non-follicular NHL. PET status at the end of this chemo-immunotherapy induction is quite controversial as a predictor of survival. Disclosures: No relevant conflicts of interest to declare.

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A Myeloablative Conditioning Regimen With Fludarabine Demonstrates Good Results In UCBT With Hematologic Malignancies, Especially Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v122.21.4575.4575 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4575-4575

Author(s):

Juan Tong ◽

Sun Zimin ◽

Liu Huilan ◽

Geng Liangquan ◽

Zheng Changcheng ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Hematologic Malignancies ◽

Good Survival ◽

Myeloablative Conditioning ◽

Blood Transplantation

Objectives We retrospectively analyzed the safety and efficacy of a myeloablative conditioning regimen without anti-thymocyte globulin (ATG) or total body irradiation (TBI) but with fludarabine (FLU) in unrelated cord blood transplantation (UCBT) for 30 patients with hematologic malignancies. Methods The myeloablative conditioning regimen consisted of FLU, busulfan (BU) and cyclophosphamide (CY). All of the patients received Cyclosporine (CSA) and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prophylaxis. Results With this conditioning regimen, we achieved high engraftment rates (96.7%) and rapid hematopoietic reconstitution. Acute GVHD occurred in 12 cases of the 29 engraftment patients (41.4%), and 6 cases (20.7%) were of grade III-IV. Chronic GVHD only occurred in 1 of 28 evaluable patients (3.6%). Twenty-three patients (76.7%) became infected, and 3 cases (10.0%) died of severe infections. Cytomegalovirus (CMV) reactivation occurred in 70.0% of the patients, but no CMV diseases were observed, nor did any patients die of CMV infection. The cumulative incidence of relapse (6.7%) was significantly reduced, and none of the acute lymphoblastic leukemia (ALL) patients relapsed. The 3-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 70.0%, respectively, representing satisfactory survival. The 3-year OS and EFS of the ALL patients was 75.0%. Discussion This conditioning regimen resulted in a high engraftment rate, rapid myeloid reconstruction and a low incidence of infection. Although there were many patients with high-risk disease and disease progression, the regimen resulted in low relapse rates and good survival. None of the ALL patients relapsed after UCBT, indicating that this conditioning regimen could be applied to more patients with ALL. Disclosures: No relevant conflicts of interest to declare.

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Spontaneous Mutations of Bcor and Jak1/2 genes Lead to an Aggressive Leukemia of B-1 Progenitor B Cells

Blood ◽

10.1182/blood.v124.21.3573.3573 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3573-3573

Author(s):

Sheryl M Gough ◽

Liat Goldberg ◽

Marbin Pineda ◽

Robert L Walker ◽

Yuelin J Zhu ◽

...

Keyword(s):

High Risk ◽

B Cell ◽

Progenitor Cell ◽

Conflicts Of Interest ◽

Fusion Gene ◽

Hot Spot ◽

Lymphoblastic Leukemia ◽

Hematologic Malignancies ◽

Janus Kinase ◽

Hematopoietic Stem

Abstract NUP98 gene fusions, generated by non-random chromosomal translocations, are associated with a wide spectrum of high risk hematologic malignancies and have been shown to alter normal hematopoietic stem and progenitor cell (HSPC) gene expression programs. A recurrent t(11;17)(p15;p13) translocation in patients with AML leads to the production of a NUP98–PHF23 (NP23) fusion gene. The consequent NP23 fusion protein retains the PHD domain, known to bind H3K4me3, and is thought to have aberrant chromatin regulation properties. We have generated a transgenic mouse model of the NUP98-PHF23 gene fusion which develops a range of hematologic malignancies, most commonly pre-T LBL and AML. However, approximately 10% of NP23 mice develop an aggressive B-1 progenitor acute lymphoblastic leukemia (pro B-1 ALL). B-1 and B-2 lymphocytes have distinct developmental pathways and are thought to represent arms of the innate and adaptive immune systems, respectively. Mature B-2 lymphocytes predominate in the peripheral circulation, and are characterized by expression of B220; whereas B-1 lymphocytes are more prevalent in the pleural and peritoneal cavities, and do not express B220. Murine B cell malignancies typically stain positive for B220, and represent transformed B-2 cells. In the present study, NP23 progenitor ALLs displayed an immunophenotype (Lin-B220- CD19+ AA4.1+) that was identical to that of the recently described B-1 progenitor cell. All B-1 progenitor ALLs exhibited clonal rearrangements of the IgH gene locus. Specifically, these rearrangements involve favored usage of 3’ VH regions, similar to observations with fetal B-1 progenitor cells, further supporting the notion that these are leukemias of B-1 progenitors. Using whole exome sequencing, we found acquired mutations in the BCL6 interacting corepressor (Bcor) gene in 5 out of 7 B-1 progenitor leukemias. The mutations were all frame shift or nonsense mutations, and were located within a 9 bp “hot spot” in Bcor exon 8. In addition, 4 of 7 cases had somatic mutations of Janus kinase 1 (Jak1) or 2 (Jak2), and 7/7 cases showed hyperphosphorylation of Stat3 or Stat5, consistent with the contention that the Jak1/2 mutations are activating mutations, and leading to a hypothesis that the NP23 pro B-1 ALLs which do not harbor Jak1/2 mutations may have acquired an unidentified mutation in the Jak-Stat pathway. Of note, Jak1/2 mutations have previously been identified in a subset of high-risk pediatric B-cell precursor ALL patients. The striking correlation between Bcor and Jak1/2 mutations, occurring specifically in a subset of NP23 leukemias, implies that these three mutations (NP23, Bcor, and Jak1/2) collaborate and provide the oncogenic setting for B-1 progenitor transformation. Disclosures No relevant conflicts of interest to declare.

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Analysis of the Expression of PHTF1 and Related Genes in Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v126.23.4988.4988 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4988-4988

Author(s):

Xin Huang ◽

Suxia Geng ◽

Jianyu Weng ◽

Zesheng Lu ◽

Linji Zeng ◽

...

Keyword(s):

Gene Expression ◽

Acute Lymphoblastic Leukemia ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Hematologic Malignancies ◽

Expression Level ◽

Newly Diagnosed ◽

Healthy Individuals ◽

Apoptosis Pathway ◽

Cell Proliferation Inhibition

Abstract Background: In the human T-cell acute lymphoblastic leukemia (T-ALL) cell line Molt-4, siRNA-mediated suppression of BCL11B expression was shown to inhibit proliferation and induce apoptosis, which may be related to PHTF1 gene expression, and the FEM1B and Apaf-1 genes may be downstream of PHTF1. In this study, we analyzed the expression level of PHTF1 and related genes in patients with ALL to clarify the role of the PHTF1-FEM1b-Apaf-1 pathway in hematologic malignancies. Methods: Fifteen newly diagnosed and untreated patients with AML, fourteen newly diagnosed and untreated patients with CML in chronic phase, twenty-two newly diagnosed and untreated patients with ALL, and six newly diagnosed and untreated patients with CLL were recruited. Peripheral blood mononuclear cells (PBMCs) from ten healthy individuals (HIs) served as controls. PBMCs were separated using the Ficoll-Hypaque gradient centrifugation method. All procedures were conducted in accordance with the guidelines of the Medical Ethics committees of the Health Bureau of Guangdong Province, China.Real-time PCR was used to determine the gene expression level of PHTF1 in hematologic malignancies. The PHTF1, BCL11B, FEM1B and Apaf-1 gene expression levels and correlations were analyzed in patients with primary ALL and healthy individuals (HIs). Results: PHTF1 overexpression was found in recently diagnosed AML (p <0.001), CML-CP (p<0.001), and ALL (p= 0.016) patients in comparison with HIs. The PHTF1 expression level in CLL patients was not significantly different compared with HIs (p= 0.165). FEM1b and Apaf-1 overexpression was found in recently diagnosed ALL (p<0.005) patients compared with HIs. Positively correlated expression was found for the PHTF1, FEM1b and Apaf-1 genes in patients with ALL (p<0.005) and HIs (p<0.005), and positively correlated expression was found for the PHTF1 and BCL11B genes in HIs (p<0.005). Conclusions: PHTF1 acts as a tumor suppressor gene, and its overexpression might be related to cell proliferation, inhibition and apoptosis. PHTF1 and BCL11B gene disorders may contribute to T-ALL pathogenesis. PHTF1 might be a therapeutic target for triggering the PHTF1-FEM1b-Apaf-1 apoptosis pathway in primary acute lymphoblastic leukemia. Acknowledgment The project was sponsored by grants from National Natural Science Foundation of China (No. 81100384, No. 81270648, No.91129720, and No. 30771980) Disclosures No relevant conflicts of interest to declare.

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Clinical Usefulness and Safety of Peripherally-Inserted Central Catethers (PICC) in Hematological Patients.

Blood ◽

10.1182/blood.v114.22.4545.4545 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4545-4545

Author(s):

Giacomo Salvatore Morano ◽

Caterina Mercanti ◽

Vincenzo Federico ◽

Angela Matturro ◽

Alessandra Micozzi ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Conflicts Of Interest ◽

Wide Spectrum ◽

Lymphoblastic Leukemia ◽

Chronic Phase ◽

Myelogenous Leukemia ◽

Haematological Malignancies ◽

Promising Alternative ◽

Advanced Phase ◽

Median Period

Abstract Abstract 4545 The use of Peripherally-Inserted Central Catheters (PICC) as an alternative to Central Venous Catethers (CVC) is becoming very frequent in different setting of patients. To highlight the role of PICC also in patients with haematological malignancies, we revised our single Institute experience from 11/2008 to 7/2009. On the whole, 33 PICCs (BARD Groshong 4 Fr) were inserted in 32 patients [M/F 11/21, median age 59.9 years, Interquartile Range (IR) 47.1 – 74.7] for a total number of 1979 days. Twelve patients had Acute Myelogenous Leukemia (AML), 3 Acute Lymphoblastic Leukemia (ALL), 6 Non-Hodgkin Lymphoma (NHL), 5 Hodgkin Lymphoma (HD), 6 Myelodysplastic/Myeloproliferative Disorders (MDS/MPD); as to disease phase, 6 patients were at onset, 10 in complete response (3 before consolidation therapy and 7 before autologous peripheral stem-cell transplantation), 5 at disease relapse, 7 in chronic phase with transfusional requirement and 4 in advanced phase. PICC was successfully inserted in all cases with US-guide (in 21 cases via basilica vein, in 11 via brachial vein and in 1 via cephalic vein). At insertion, platelets count was < 50 × 109/l in 17/33 cases (51.5%) while WBC count was < 1.0 × 109/l in 6/33 cases (18.1%). An accidental PICC extraction occurred after 13 days; in addition, there were 2/33 (6.0%) (0,03/1000 gg) thrombophlebitic complications after 15 and 21 days respectively and 6/33 (18.1%)(0.10/1000 gg) infective complications [4 sepsis catheter-related from Staphylococci (3) or Acromobacter (1) and 2 local flogistic infiltration]. On the whole, 17/33 PICCs (51.5%) were removed after a median period of 39 days (IR 17 – 64); the reasons for removal were completion of treatment in 4 patients, death unrelated to the PICC in 6 and catheter-related complications in 7 (5 for infection, 1 for thrombosis and 1 for accidental extraction). The remaining 16/33 PICCs (48.5%) are still in use after a median period of 73 days (IR 30 – 93). In conclusion, PICC seems to be a useful, safe and promising alternative to conventional CVC for many haematological malignancies in a wide spectrum of clinical settings, ranging from intensive chemotherapy (including autotransplant procedure) to chronic management and very advanced phases requiring palliative approach. Disclosures: No relevant conflicts of interest to declare.

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Excessive Early Mortality Drives Poor Long Term Outcomes Among Older Patients With Classical Hodgkin Lymphoma: A Population Study

Blood ◽

10.1182/blood.v122.21.1742.1742 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1742-1742

Author(s):

Luciano J. Costa

Keyword(s):

Hodgkin Lymphoma ◽

Older Patients ◽

Conflicts Of Interest ◽

Age At Diagnosis ◽

Classical Hodgkin Lymphoma ◽

Nodal Disease ◽

Early Stage Disease ◽

Younger Patients ◽

Risk Of Death ◽

One Year

Background Classical Hodgkin Lymphoma (cHL) is a highly curable malignancy in young adults. Most of the information available on natural history and management of cHL comes from series and clinical trials in young patients. There is limited information on the outcomes of older patients with cHL Methods We analyzed the characteristics and outcomes of a large contemporary cohort of cHL patients ≥ 65 years diagnosed in the US and reported to the Surveillance Epidemiology and End Results program (SEER-18). Inclusion criteria consisted of diagnosis of cHL as first malignant neoplasm, year of diagnosis 2000-2010, known stage and known race. Cases reported from death certificate or autopsy only were excluded. Information retrieved contained age at diagnosis, year of diagnosis, race, sex, histological subtype, stage, presence of extra-nodal disease and survival time. Characteristics of cHL in patients ≥ 65 years (older) were compared to those < 65 years (younger). We subsequently estimated relative survival (RS) for different stages and age strata among older patients comparing with outcomes in younger patients. Results There were 20815 cases of cHL reported during the period with median follow up of 48 months, including 2884 (13.8%) cases in older patients. Older patients were more likely to present with extra-nodal disease (4.7% vs. 2.2%, P< 0.001), advanced stage (52.6% vs. 37.3%, P<0.001) and with lymphocyte depleted cHL (3.3% vs. 0.9%) or mixed cellularity cHL (22.5% vs. 11.3%, P<0.001) than younger patients. Additionally, older cHL patients with early stage disease were less likely to receive radiation therapy (35.6% vs. 48.2%, P<0.001). RS at one year (64% vs. 95.7%, P<001) and 5-years (49% vs. 89%, P<0.001) was much inferior in older than in younger patients, even when stratified by early (I and II) and advanced (III and IV) stages (Figure). RS deteriorated quickly with increasing age at diagnosis. One year RS was 73.9%, 56.3% and 43.3% and 5-years RS was 57.9%, 41.6% and 30.4% for patients 65-74, 75-84 and 85+ years, respectively. Even with adjustment for histology, sex, year of diagnosis and race, patients 65-74 years (HR = 4.81, 95%CI 4.41-5.26, P<0.001) 75-84 years (HR = 9.60, 95% CI 8.78-10.49, P<0.001) and 85+ years (HR = 16.19, 95% CI 14.15-18.51, P<0.001) were at a much higher risk of death than younger cHL patients. Conclusion cHL has distinct presentation and far worse prognosis in older patients with excessive early (<1 year) mortality. There is a need to further understand patterns of treatment failure and develop age-specific therapeutic interventions for this group. Disclosures: No relevant conflicts of interest to declare.

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Malignant hematologic diseases in adolescents and young adults

Blood ◽

10.1182/blood-2010-12-283093 ◽

2011 ◽

Vol 117 (22) ◽

pp. 5803-5815 ◽

Cited By ~ 57

Author(s):

William A. Wood ◽

Stephanie J. Lee

Keyword(s):

Young Adults ◽

Hodgkin Lymphoma ◽

Care Delivery ◽

Health Care Systems ◽

Lymphoblastic Leukemia ◽

Hematologic Malignancies ◽

Adolescents And Young Adults ◽

Adult Health ◽

Non Hodgkin Lymphoma ◽

Care Systems

Abstract Adolescents and young adults (AYA) with cancer have been designated as a vulnerable population by the National Cancer Institute. This group, defined by the ages of 16-39 years, has not enjoyed the same survival improvements over the past several decades as older and younger cohorts. Several barriers prevent the optimal delivery of oncologic care in this subpopulation. This review will describe these challenges in the context of the major hematologic malignancies affecting this population (acute lymphoblastic leukemia [ALL], acute myeloid leukemia [AML], Hodgkin lymphoma [HL], and non-Hodgkin lymphoma [NHL]). For example, historical differences in care delivery between pediatric and adult health care systems have created confusion about optimal treatment planning for AYAs, a population that spans the pediatric-adult divide. In the case of ALL, retrospective studies have demonstrated significantly better outcomes when AYAs are treated according to pediatric and not adult protocols. Additional challenges more specific to AYAs include increased treatment-related toxicity relative to younger patients; less access to care and, specifically, access to clinical trials; lower adherence to medications and treatment plans; and psychosocial stressors relevant to individuals at this stage of life. Recognizing and responding to these challenges in AYAs may create opportunities to improve the cancer outcomes of this group.

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Central Nervous System (CNS) Infiltration Assessment Using Cerebrospinal Fluid Flow Cytometry in Hematologic Malignancies: A Single Center Retrospective Analysis of Clinical Outcomes

Blood ◽

10.1182/blood-2019-127558 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5773-5773

Author(s):

Eduardo Cerello Chapchap ◽

Carolina Feres ◽

Laiz Cameirão Bento ◽

Daniela Schimidell ◽

Rodolfo Patussi Correia ◽

...

Keyword(s):

Central Nervous System ◽

Flow Cytometry ◽

Overall Survival ◽

Nervous System ◽

Clinical Outcomes ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Hematologic Malignancies ◽

Clinical Approach ◽

Cns Disease

INTRODUCTION: The detection of central nervous system (CNS) disease in hematologic malignancies is important to guide optimal therapeutic approach, refine prognosis and understand patient`s unexplained neurologic symptoms. Newer flow cytometry (FC) techniques are emerging, also there are increasingly reports of higher accuracy than routine cytospin. Moreover, these are becoming incorporated more frequently in clinical work up practices. However, there is still uncertainty on clinical approach of CNS-positive patients, detected only by FC. OBJECTIVE: To analyze accuracy and clinical outcomes of CNS disease by cytopsin or FC in patients with hematologic malignancies. MATERIAL AND METHODS: FC cerebrospinal samples and medical charts of 84 consecutive patients evaluated for CNS infiltration by hematologic malignancies from January/2014 to December/2016 were reviewed. Statistical analysis were done with SPSS and STATA softwares. RESULTS: Baseline patients characteristics were: male (62%), median age 53 years; non-hodgkin lymphoma (52%), Acute Lymphoblastic Leukemia (26%), Acute Myeloblastic Leukemia (15,5%), Multiple Myeloma (6,5%); CNS-positivity rates according to each technique were: Cytopsin-/FC- (71,4%), Cytospin+ (14,3%), Cytospin-/FC+ (14,3%); CNS-disease was detected by FC in 32,3%, while for cytospin was 16,7%. Overall survival was 71,4% and relapse rate 38,1% at 2,5 years of median follow-up. Relapsed (HR: 2,76 p0,023) and CNS-positivity (HR: 2,01 p0,037) patients were significantly associated with an inferior overall survival. Also, progression free survival (PFS) of Cytospin-/FC+ was significantly inferior than CNS-negative subgroup (HR: 2,93 p0,022). CONCLUSION: FC sensitivity appears to be higher than classicaly cytospin methods to detect CNS disease, also CNS-positivity was associated with a worse prognosis, as well as in the subset of patients Cytospin-/FC+. Further studies with a more homogeneous cohort and larger sample sizes are needed to validate our findings. Figure Disclosures No relevant conflicts of interest to declare.

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Is There an Increased Risk of ALL in Patients with First Cancers Treated with Radiotherapy and/or Chemotherapy?

Blood ◽

10.1182/blood-2018-99-118207 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 900-900

Author(s):

Remco J Molenaar ◽

Tomas Radivoyevitch ◽

Aaron T. Gerds ◽

Aziz Nazha ◽

Hetty E. Carraway ◽

...

Keyword(s):

Breast Cancer ◽

Board Of Directors ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Lymphoblastic Leukemia ◽

Age At Diagnosis ◽

Regression Analyses ◽

Advisory Committees ◽

Increased Risk ◽

The Us

Abstract Background External-beam radiotherapy (RT) and chemotherapy (CT) are commonly used modalities in cancer therapy and have been associated with increased risk of second hematological malignancies, especially myeloid neoplasms. Acute lymphoblastic leukemia (ALL) is typically not considered a treatment-related complication and the risk of ALL in patients treated with chemotherapy and radiation for other cancers is poorly defined. In this study, we interrogated the US Surveillance Epidemiology and End Results (SEER) registry to analyze the risks of ALL in cancer patients treated with RT, CT or combined modality regimens at the population level. Methods We used our previously validated R program, SEERaBomb (Leukemia 2016; 30: 285-94) to query all 18 SEER registries, 1973-2014. We identified all first cancer cases treated with RT and/or CT that subsequently developed ALL ≥1 year after diagnosis of the first cancer. First cancer cases of lymphoid lineage were excluded. Diagnosis was derived from the International Classification of Diseases. Relative risk (RR) time courses for developing ALL after treatment of first cancers was calculated based on the ratio of the observed and expected cases of ALL. The expected number of ALL patients was calculated using the background incidence rates of ALL in the US population and the person-years at risk for ALL after treatment of first cancer. RRs were adjusted for age at diagnosis, sex, and year of diagnosis. Multivariate Cox regression analyses were used to calculate hazards of ALL development to adjust for more covariates. Results In total, 4,851,222 eligible first cancer patients were identified, of whom 821,004 (17%) received RT only, 571,035 (12%) received CT only, 488,930 (10%) received RT + CT and 2,970,253 (61%) received neither. A total of 849 patients developed ALL; 176 (21%) in the RT only group, 137 (16%) in the CT only group, 106 (12%) in the RT + CT group and 430 (51%) in the no RT/CT group. Compared to the risk in general population, patients treated with CT or RT had an elevated risk of developing ALL in the first 10 years after first cancer diagnosis (RR for RT only, 1.59 [95% CI 1.33-1.88] P < 0.0001; RR for CT only, 3.47 [2.87-4.16] P < 0.0001; RR for CT + RT, 3.22 [2.69-3.97] P < 0.0001). Patients with prior cancers but not treated with these modalities had no increased risks for ALL (RR for no RT/CT, 1.05 [0.93-1.17] P = 0.44; see Figure). In a more homogeneous cohort of breast cancer patients, elevated risks of developing ALL in the first 10 years after breast cancer diagnosis were seen in patients treated with CT + RT (RR, 3.46 [2.46-4.73] P < 0.0001) or RT only (RR, 1.82 [1.33-2.43] P = 0.0001) but not in those treated with CT only (RR, 1.76 [0.98-2.89] P = 0.06) or no CT/RT (RR, 0.77 [0.53-1.07] P = 0.15). In multivariate regression analyses in the entire cohort of cancer patients, significant predictors for subsequent ALL were younger age at diagnosis, male sex, receipt of CT or RT and if a non-lymphoid hematological malignancy preceded development of ALL (Table 1). Among patients with solid tumors as first cancers, CT + RT was associated with the highest hazards for developing ALL followed by RT only and then CT. Among patients with hematological first cancers, CT only, but not CT + RT or RT only, was associated with increased hazards for ALL. Conclusion Among patients treated for a first cancer, receipt of RT and/or CT was associated with higher relative risks and hazards for developing ALL than those not receiving cytotoxic modalities. Patients with hematologic first cancers (myeloid lineage or plasma cell dyscrasias) had the highest hazards of developing ALL as second cancer. When considering the risk kinetics and subgroup analyses in patients with solid first cancers, RT only or RT + CT, but not CT only, associate with increased risks for ALL. To our knowledge this is the largest evaluation of the risk of ALL in cancer patients treated with various modalities. Differentially elevated risks of ALL observed in cancer cohorts based on the treatment modality that was received for a prior cancer suggests a possible biological mechanism that needs to be explored further. Disclosures Gerds: Celgene: Consultancy; CTI Biopharma: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy. Nazha:MEI: Consultancy. Carraway:Jazz: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; FibroGen: Consultancy; Novartis: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria. Maciejewski:Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.

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Combination of Haploidentical Hematopoietic with Low-Dose TBI and Cord Blood Transplantation for Hematologic Malignancies

Blood ◽

10.1182/blood-2021-152290 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4856-4856

Author(s):

Shenxian Qian ◽

Fan Yang ◽

Pengfei Shi

Keyword(s):

Cord Blood ◽

Low Dose ◽

Conflicts Of Interest ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Cord Blood Transplantation ◽

Hematologic Malignancies ◽

Hla Typing ◽

Blood Transplantation ◽

Cell Counts

Abstract Objective: To evaluate the efficacy and safety of the combination of haploidentical hematopoietic with low-doseTotal body irradiation（TBI）and cord blood transplantation for hematologic malignancies. Methods: This study was conducted as a retrospective review of medical records of 5 patients with hematologic malignancies who received a combination of haploidentical hematopoietic with low-dose TBI and cord blood transplantation at Affiliated HangZhou first people's hospital of Zhejiang University school of medicine, from March to June 2021. Results: 5 patients were included for the analysis. There were 1 acute myeloid leukemia (AML),2 acute lymphoblastic leukemia (ALL) and 2 Non-Hodgkin's Lymphoma(NHL). The minimal residual disease (MRD) of the two patients with ALL was positive before allo-HCT.Median age of patients at the time of allo-HCT was 30 years (range 21-63 years). All patients received low-dose TBI(4-6GY) +antithymocyte globulin（ATG）based conditioning.Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. The median values of absolute total nucleated cell counts were 139.0 (80.8-240.0) × 10 7 / kg in The haploidentical grafts and 2.25 (1.32-3.10)× 10 7 / kg in the cord blood units,respectively. The median doses of CD34+ cells infused were 28.6 (22.0-51.1) × 10 5 / kg in the haploidentical grafts and 1.5 (1.0-3.5)×10 5/kg in the cord blood units, respectively.All patients attained complete engraftment,of which 3 were haploidentical engraftment and 2 were mixed hematopoietic chimerism that included haploidentical and cord blood engraftment.The median time to neutrophil engraftment was 12 (10-22) days and 13 (11-22) days for platelets. All patients were in complete remission with MRD-negetive during a median follow-up of 83 (34-136) days.No patients developed grade II-IV acute graft versus host desease. Conclusion:The results suggested that the combination of haploidentical hematopoietic with low-dose TBI and cord blood transplantation may potentially improve the outcome of HSCT. It offers a transplant alternative for patients with hematologic malignancies who lack matching donors. Disclosures No relevant conflicts of interest to declare.

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