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PURPOSE: To analyze the rates of concordance in the diagnosis of various hematological malignancies among patients referred to a tertiary cancer center, comparing the referring diagnosis with the final diagnosis at the M.D. Anderson Cancer Center. PATIENTS AND METHODS: This was a cross-sectional study analyzing the 409 patients referred to the M.D. Anderson Leukemia Service in 1995 in whom a bone marrow examination was performed by the referring physician and in whom this examination was repeated at our institution. We also analyzed 100 cases, including 84 of the 409 referred patients for whom the diagnostic outside bone marrow slide had been sent for review. RESULTS: The overall concordance rate was 73%. In 18% discordances were present and considered of major importance (affecting treatment and/or prognosis) while in 9% there were minor discordances. Major discordance rates were 2% for chronic lymphocytic leukemic leukemia and 5% for chronic myelogenous leukemia, but 29% for acute myelogenous leukemia (79 patients), 43% for acute promyelocytic leukemia (7 patients), 19% for acute Iymphocytic leukemia (42 patients), 57% for hairy cell leukemia (7 patients), and 23% for the myelodysplastic syndromes (75 patients). The concordance rate was 76% in the 100 cases in which bone marrow specimens permitted comparison of the morphologic diagnosis made by M.D. Anderson and the referring physician using the same slide, with a rate of 75% in the acute leukemias as finally diagnosed at our institution. CONCLUSION: Although in the majority of cases the referring physicians and the specialty service agreed on diagnosis, major discordance occurs in a significant number of cases, including highly treatable diseases such as acute promyelocystic leukemia and hairy cell leukemia. Am J Med. 1998;104: 246-251. [C] 1998 by Excerpta Medica, Inc.

The purpose of this review is to provide a framework for the cardiovascular evaluation and management of patients undergoing hematopoietic cell transplantation (HCT). To accomplish this, we have performed an extensive literature review, critically analyzed the available evidence, and developed a set of recommendations to guide best practice. Herein, we discuss the cardiovascular risk profile of patients undergoing HCT along with putative mechanisms of HCT-induced cardiovascular injury. We then present an algorithm for cardiovascular testing and risk mitigation of potential recipients. Last, we address the management of the most prevalent cardiovascular conditions associated with HCT recipients.

Mukherjee: Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Caimi:Genentech: Speakers Bureau; Gilead: Consultancy; Roche: Research Funding; Novartis: Consultancy. Maciejewski:Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Speakers Bureau; Apellis Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Speakers Bureau. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

ATG appears to reduce the incidence of acute and chronic GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Potential risks of this strategy include viral reactivation, delayed immune recovery and increased relapse rates. The ideal dosing of rabbit ATG in this context is largely unknown. We therefore hypothesized that low dose ATG would reduce the incidence of acute and chronic GVHD in matched unrelated donor (MUD) transplants without compromising survival and relapse rate. A retrospective analysis was performed of a cohort of high-risk MUD HSCT recipients treated since year 2013, when our practice changed to include rabbit ATG at 3 mg/Kg for all MUD transplants at the Case Medical Center in Cleveland, Ohio. Herein we present the results of this analysis.

The median age for the Post- CY group and control group was 61 (range, 39–72) and 62 years (range, 37–72). Eight-one (81) % of patients in both groups had AML or MDS, 3% had ALL and 16% had NHL or CLL. Fifty-nine (59) % of patients in both groups had unrelated donors and received ATG in the conditioning. Disease status for the Post-CY and control groups respectively were CR1: 14 and 14%, CR2: 8 and 11%, >CR2: 38 and 32% and Primary Induction Failure / Untreated: 40 and 32%. Seventy (70) % of the post-CY group received BM versus 48% of the control group, whereas sex mismatching (Male donor for Female patient) occurred in 22% of the post-Cy and 8% of the control group. The cumulative incidence of grade II-IV acute GVHD and chronic GVHD in the post-CY and control groups were: 46% versus 19% (Hazard Ratio (HR): 2.8, 95% CI, 1.1–6.7; p=0.02) and 14% versus 21% (HR: 0.8, 95% CI, 0.2–2.6, p=0.7). Grades III/IV acute GVHD occurred in 14% (95% CI, 6–32) of the patients in the post-CY group whereas there were no cases of grade III/IV in the control group (p=0.02). Overall, progression-free and non-relapse mortality at 2-years are shown in the table below.Post-transplant CY following RIC is associated with higher rates of acute GVHD, with resultant trends for higher non-relapse mortality and lower overall survival when compared to tacrolimus and mini-dose MTX. The use of post-transplant CY as a sole GVHD prophylaxis regimen should be avoided following RIC transplant in matched-related and unrelated donors.Off Label Use: azacitidine: off-label use as maintenance therapy following allogeneic stem cell transplant for MDS/AML.

Abstract 2032This icon denotes a clinically relevant abstract

No relevant conflicts of interest to declare.

A total of 851 consecutive autologous apheresis procedures were performed at M.D. Anderson Cancer Center between January 2005 and December 2009. We randomly selected half (N=413) of this study population to serve as a study sample (described in table), and preserved the remaining for validation studies. In this study population, we observed that 96% of patients with PB pre-apheresis CD34+ counts of >40/μL collected >2×106 CD34+cells/Kg on the first day of apheresis. We sought to determine patient and disease characteristics that are associated with higher PB pre-apheresis CD34+ counts (>40/μL). These factors included patient age (quartiles), gender, weight (quartiles), diagnosis (Multiple Myeloma vs. Hodgkin's and Non-Hodgkin's Lymphoma), disease status at transplant (remission vs. active disease), number of prior chemotherapy regimens (< 2 vs. ≥2), blood count on day of collection: hemoglobin level (≤10 vs. >10 g/dL), WBC (<4 vs. ≥ 4 ×109/L), absolute neutrophil count [ANC] (< vs.≥ median), and platelet count (≤150 vs. <150 ×109/L); and number days (≤ vs. > median) from the beginning of mobilization to the first apheresis procedure.On univariate analysis, shorter duration from beginning of mobilization therapy to first day of apheresis (odds ratio [OR] =4.7, p <0.001), and weight >95 Kg (OR=1.8, p=0.01), were significantly associated with a PB CD34+count >40/μL; whereas a diagnosis of Multiple Myeloma (OR=0.5, p=0.002), age >60 years (OR=0.6, p=0.009), pre-apheresis WBC <4 × 109/L (OR=0.5, p=0.004) and ANC (< median p=0.003) were significantly associated with PB CD34+ counts of ≤ 40/μL. These factors, with the exception of age, remained significant on multivariate analysis. Shorter duration of mobilization (OR=8.1, p<0.001) had the strongest association with PB CD34+ count >40/μL. A diagnosis of Multiple Myeloma was associated with lower PB CD34+ count in patients who had a shorter mobilization course (OR=0.3, p<0.001), but not in those who took longer to mobilize. Lower WBC and ANC counts were associated with lower PB CD34+ count, and this effect was more pronounced for patients who had both low WBC and ANC (OR=0.4, p=0.001) than for those who had low ANC but high WBC count (OR=0.5, p=0.025). Weight >95 Kg was still associated with higher PB CD34+ count, (OR=1.9, p 0.01). There was no association between PB CD34+ count and any of the remaining factors evaluated.Our data suggest that patients who take longer to mobilize, have low WBC and [ANC] pre-apheresis might benefit from early intervention with novel mobilization strategies.Totals may vary because of missing data.Popat: Otsuka: Research Funding.

Gupta: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

BACKGROUND: Both autologous and allogeneic stem cell transplantation (SCT) are potentially curative treatment options for patients with hematologic malignancies. Due to a high risk of regimen-related toxicity, only patients with satisfactory organ-system function are considered eligible for this treatment. A low left ventricular ejection fraction (LVEF) of ≤ 45% is considered to be a major risk factor for post-transplant cardiac toxicity and non-relapse mortality (NRM). However, many patients with advanced hematologic malignancies and low LVEF can potentially benefit from this therapy. To address this issue, we studied the incidence of cardiac toxicity and NRM in 89 patients with low LVEF undergoing SCT. METHODS: We performed a retrospective analysis on 89 patients with impaired cardiac function, who underwent an autologous (33 patients) or allogeneic (56 patients) SCT between January 2000 and February 2006 at our institution. Pre-transplant evaluation included bidimensional echocardiogram and an electrocardiogram. Cardiac toxicity was defined as congestive heart failure (CHF), atrial/ventricular arrhythmia or acute myocardial ischemia. In the allogeneic group, 22 patients received a myeloablative (16 busulfan-based, 6 TBI-based), while 34 patients received a fludarabine-based reduced-intensity preparative regimen. Twenty-three patients (41%) received allo SCT from an unrelated donor. The majority of patients in the autologous group received BEAM (with rituximab or IL-2) based regimen (24 patients) and 6 patients received high dose melphalan. RESULTS: 57% of the allogeneic transplants were for acute leukemia. 76% of autologous transplant recipients had Hodgkin’s or non-Hodgkin’s lymphoma. Baseline LVEF, within 30 days prior to SCT, ranged from 20 to 45%. After a minimum of 6-month follow up, cardiac toxicity was seen in 6 patients in the auto SCT group and 6 patients in the allo SCT group (13%). In 9 of the 12 patients toxicity occurred within 60 days of SCT. Major causes of cardiac toxicity were CHF in 6 patients (7%) and atrial fibrillation in 5 patients (6%). Two patients had both CHF and AF. There were no documented episodes of acute myocardial ischemia. Median time to develop a cardiac event was 23 days from SCT (range, 9–200 days). Cumulative incidence of NRM at 100 days was 15% (95% CI 9–24). Only 1 death was directly attributable to a cardiac cause. These results are comparable to SCT performed in patients with normal LVEF. On univariate analysis age > 60 years at the time of SCT and history of smoking were significant predictors for development of cardiac toxicity after SCT. Prior history of smoking remained significant on multivariate analysis (HR 5.7, 95% CI 1.2–29, P=0.03). LVEF, type of transplant or the underlying disease did not emerge as significant predictors of post-transplant cardiac toxicity or NRM. Median survival was worse in patients who developed cardiac complications after SCT (median survival 108 days versus 889 days respectively). CONCLUSIONS: Both allogeneic and autologous SCT are feasible in patients with hematologic malignancies and low LVEF. A prospective study with stratification for cardiac risk factors is warranted in patients with low LVEF.

Both G-CSF and GM-CSF (alone or in combination) may be used for mobilization of hematopoietic progenitor cells in patients undergoing autologous stem cell transplantation (ASCT). It has been suggested that GM-CSF use during mobilization may impact graft composition and therefore clinical outcomes. METHODS: We prospectively evaluated patients ≤ 70 years old with relapsed CD20+ NHL who were candidates for ASCT. Additional eligibility criteria included adequate marrow and organ function. Patients with history of pelvic radiation, > 3 prior chemoregimens or > 6 cycles of fludarabine chemotherapy were excluded. Patients recieved chemotherapy with ifosfamide 3.33 g/m2 daily × 3 days, etoposide 150 mg/m2 × 6 doses and rituximab (375 mg/m2 on day 1 and 1 g/m2 on day 8). Using a Bayesian adaptive randomization based on treatment outcomes, patient’s were randomized to receive G-CSF 12 μg/kg/d (Group G) or G-CSF 12 μg/kg/d plus GM-CSF 500 μg/d (Group G/GM). We assumed that the success rate for each treatment arm had a β prior distribution with mean 0.90 and variance 0.03. Cytokines started 24 hours after completion of chemotherapy and continued until completion of apheresis. RESULTS: Forty-three patients were randomized to Group G and 41 patients to Group G/GM. In each arm 1 patient withdrew consent after randomization. Baseline characteristics were similar in the 2 groups (Table 1). Both regimens were equally well tolerated. Data are presented as intent to treat analysis. Thirty-nine patients (90.7%) in Group G and 35 patients (85.4%) in Group G/GM collected ≥ 4 × 106 CD34+ cells/kg. The probability that Group G has a higher success rate than Group G/GM is 0.778. The median CD34+ cell dose collected was 10.3 × 106/kg (range, 0.1–59) and 7.5 × 106/kg (range, 0.7–73) in Groups G and G/GM respectively (P=NS). A median of 2 apheresis procedures were required in both arms. Seventy-three patients have undergone ASCT. After a median follow up time of 14.5 months (range, 0.6–38.5) in Group G and 14.0 months (range, 1.1–39.9) in Group G/GM, the 3 year PFS is 75% (95% CI 57.9–99.4) and 77% (95% CI 65–91.5) respectively (P=0.41). CONCLUSION: Our study does not support the hypothesis that using G-CSF plus GM-CSF versus G-CSF alone for progenitor cell mobilization alters graft composition in a way that impacts clinical outcomes after ASCT for NHLs. Baseline Patient Characteristics *Missing data 1 patient G-CSF, N (%) G-CSF + GM-CSF, N (%) 43 (51) 41 (49) AGE <39 4 (9.3) 3 (7.3) 40–59 29 (57.4) 26 (63.5) >59 10 (23.2) 12 (29.3) GENDER (Male/Female) 29/14 (67.4/32.6) 24/17 (58.5/41.5) HISTOLOGY Low grade 4 (9.3) 7 (17.1) Intermediate grade 39 (90.7) 34 (82.9) ANN ARBOR STAGE >I 18 (41.9) 18 (43.9) LDH>Normal* 15 (34.9) 11 (27.5) Figure Figure