Vascular access via peripherally inserted central venous catheters (PICCs): experience in 40 patients with acute myeloid leukemia at a single institute.

Reliable long-term vascular access is essential for the treatment of patients with acute myeloid leukemia (AML). Although peripherally inserted central catheters (PICCs) have been in use for many years, little data exist on their use in patients receiving intensive chemotherapy. We retrospectively reviewed all AML patients who had a PICC inserted between July 95 and May 98. Fifty two PICCs were inserted in 40 patients with AML. Thirty three PICCs were inserted during severe thrombocytopenia (platelets < 50 x 10(9)/L), and 31 during severe neutropenia (neutrophils < 0.5 x 10(9)/L). Mean catheter duration was 82 (median 63, range 3-441) days for a total of 4274 catheter days. A mean of 1.8 chemotherapy courses were administered via each PICC. There were 5 early complications of PICC placement. Other mechanical complications occurred in 14 catheters and phlebitis in 12. Twenty blood stream infections (BSI) occurred in 17 patients. All BSIs occurred during neutropenia. Seventeen PICCs were removed due to the following complications - phlebitis (11), possible catheter related BSI (4), mechanical reasons in 3 (2 with concomitant phlebitis) and persistent fever (1). PICC duration was significantly shorter in these 17 catheters (52.9 v 96.4 days in the other 35, p=0.0289). We conclude that PICCs provide long-term vascular access with an acceptable complication rate in patients with AML. However, a randomised trial is required before PICCs can be considered an alternative to tunneled central venous catheters in these patients.     

Antifungal Prophylaxis in AML Patients Receiving Intensive Induction Chemotherapy: A Prospective Observational Study From the Acute Leukaemia French Association (ALFA) Group

BackgroundAlthough recommended in patients with acute myeloblastic leukaemia (AML) after induction chemotherapy, real-life use of antifungal prophylaxis (AFP) is different among centres.Materials and MethodsThis is an ancillary study to a randomized trial on intensive induction chemotherapy in AML patients (ALFA-0702/NCT00932412), where AFP with posaconazole was recommended. IFIs were graded by investigators and by central reviewers according to the revised EORTC definitions. Experts conclusions were compared to the investigators’ ones.ResultsA total of 677 patients were included. Four AFP strategies were reported: Group-1: no AFP (n = 203, 30%), Group-2: posaconazole (n = 241, 36%), Group-3: posaconazole with other AFP (n = 142, 21%), Group-4: other AFP (n = 91, 13%). Experts graded more IFI than investigators: proven/probable IFI, 9.0% (n = 61) versus 6.2% (n = 42). The cumulative incidence at day60 of probable/proven IFI was 13.9% (Group-1); 7.9% (Group-2); 5.6% (Group-3); and 6.6% (Group-4). IFI onset was 26 (19-31) days after induction in Groups 2-3, versus 16 (9-25) days in Group 1 and 20 (12-24) days in Group 4 (P< .001). After a median follow-up of 27.5 months (0.4-73.4), the mortality rate was 38.3%, with 5.4% attributed to IFI. In multivariate analysis, IFI occurrence was an independent risk of death (HR5.63, 95%-CI 2.62-12.08, P< .001). EORTC recommendations were applied in only 57% of patients. In patients without IFI, the rate of AML complete remission was higher.ConclusionsIn AML patients, AFP delayed the onset of IFI in addition of decreasing their rate. The frequent misidentification of IFI impacts their appropriate management according to recommendations. hematological remission was more frequent in patients without IFI.     

Clinical profile of gilteritinib in Japanese patients with relapsed/refractory acute myeloid leukemia: An open‐label phase 1 study

Gilteritinib, a novel, highly specific, potent fms‐like tyrosine kinase 3/AXL inhibitor, demonstrated antileukemic activity in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). In this open‐label phase 1 study (NCT02181660), Japanese patients (aged ≥18 years) with R/R AML received once‐daily gilteritinib, escalating from 20 to 300 mg/d. Primary endpoints were safety/tolerability, including the maximum tolerated dose (MTD) and the recommended dose (RD); secondary endpoints were antileukemic activity and pharmacokinetics (PK). Twenty‐four Japanese patients with R/R AML received once‐daily oral gilteritinib in 1 of 6 dose‐escalation cohorts (20, 40, 80, 120, 200, and 300 mg/d). Gilteritinib was well tolerated. The MTD was 200 mg/d; dose‐limiting toxicities were grade 3 tumor lysis syndrome (120 mg/d; n = 1); and grade 3 elevated blood lactate dehydrogenase, amylase, blood creatine phosphokinase levels, and syncope (all n = 2; 300 mg/d). The RD was 120 mg/d. The most common drug‐related grade ≥3 adverse events were thrombocytopenia (n = 4 [16.7%]) and increased blood creatine phosphokinase (n = 3 [12.5%]). Gilteritinib had a dose‐proportional PK profile. Among patients with mutated fms‐like tyrosine kinase 3, the overall response rate (ORR) was 80% (n = 4 of 5; complete remission [CR] with incomplete platelet recovery, 1 [20%]; CR with incomplete hematologic recovery, 2 [40%]; partial remission (PR), 1 [20%]). Among patients with wild‐type fms‐like tyrosine kinase 3, ORR was 36.4%; (n = 4 of 11; CR, 1 [9.1%]; CR with incomplete platelet recovery, 2 [18.2%]; PR, 1 [9.1%]). In conclusion, gilteritinib was well tolerated and demonstrated antileukemic activity in a Japanese R/R AML population.     

Defining Acute Myeloid Leukemia Ontogeny in Older Patients

BackgroundAcute myeloid leukemia (AML) in elderly patients is associated with poor outcomes and often arises from antecedent hematologic disorders (AHD), classified as secondary AML (sAML).Patients and MethodsTo validate the use of somatic mutations to determine AML ontogeny in the elderly population, we identified 178 elderly (> 70 years) patients with AML with NexGen Sequencing data. Patients were divided clinically into primary AML (pAML) or sAML based on prior history of AHD. Patients were then reclassified into 4 groups based on somatic mutations and cytogenetics as suggested by Lindsley et al: group 1 (pAML) with CBF rearrangements, 11q23/MLL, and NPM1 mutation (MT); group 2 (sAML) with SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 MT; group 3 with TP53 MT; and group 4 as not otherwise specified (NOS).ResultsBased on clinical criteria, 95 patients were classified as pAML and 82 patients as sAML. Based on the AML ontogeny proposed, 8 patients were classified as pAML, 72 patients as sAML, 28 patients had TP53 MT, and 70 patients were classified as NOS. The median overall survival was 22.4,14, 2.8, and 11.2 months, respectively. Clinical versus molecular classification was discordant where 25% (n = 2) of patients classified as pAML by molecular signature had a history of AHD, whereas 44% (n = 32) of patients classified molecularly as sAML had no prior AHD. In the TP53 MT and NOS categories, 37% (n = 28) and 43% (n = 70) of patients had AHD, respectively.ConclusionOur data shows that molecular annotation of elderly patients with AML reclassifies a significant proportion of patients as sAML, which may have therapeutic implications.     

Excellent Survival Outcomes of Pediatric Patients With Acute Myeloid Leukemia Treated With the MASPORE 2006 Protocol

PurposeTo determine the prognostic factors in pediatric patients with acute myeloid leukemia (AML) and to assess whether their outcomes have improved over time.Patients and MethodsSixty-two patients with AML excluding acute promyelocytic leukemia were retrospectively analyzed. Patients in the earlier cohort (n = 36) were treated on the Medical Research Council (MRC) AML12 protocol, whereas those in the recent cohort (n = 26) were treated on the Malaysia–Singapore AML protocol (MASPORE 2006), which differed in terms of risk group stratification, cumulative anthracycline dose, and timing of hematopoietic stem-cell transplantation for high-risk patients.ResultsSignificant improvements in 10-year overall survival and event-free survival were observed in patients treated with the recent MASPORE 2006 protocol compared to the earlier MRC AML12 protocol (overall survival: 88.0% ± 6.5% vs 50.1% ± 8.6%, P = .002; event-free survival: 72.1% ± 9.0 vs 50.1% ± 8.6%, P = .045). In univariate analysis, patients in the recent cohort had significantly lower intensive care unit admission rate (11.5% vs 47.2%, P = .005) and numerically lower relapse rate (26.9% vs 50.0%, P = .068) compared to the earlier cohort. Multivariate analysis showed that treatment protocol was the only independent predictive factor for overall survival (hazard ratio = 0.21; 95% confidence interval, 0.06-0.73, P = .014).ConclusionOutcomes of pediatric AML patients have improved over time. The more recent MASPORE 2006 protocol led to significant improvement in long-term survival rates and reduction in intensive care unit admission rate.     

Multivariate analysis on complications of central venous access devices in children with cancer and severe disease influenced by catheter tip position and vessel insertion site (A STROBE-compliant study)

ContextReliable long-term central venous access device (CVAD) is essential for the management of pediatric patients with cancer or chronic diseases. However, there is no general consensus for optimal catheter tip location and vessel insertion site in children.ObjectiveThis single center study analyzes the risk of complications associated with long-term upper body CVAD and evaluates them with respect to catheter tip location as well as vessel insertion site.DesignPediatric patients who received long-term upper body CVAD from January 2008 through April 2017 and underwent radiographic documentation of the tip location were retrospectively included in the study. Data on demographics, catheter tip location on chest x-ray, intraoperative vessel insertion sites and postoperative complications were analyzed. Catheter tip location was categorized as “high” (above the right mainstem bronchus), “medium” (at the level of the bronchus), and “low” (below the right mainstem bronchus). Distance to the carina was measured as well.ResultsA total of 396 patients, 74.7% suffering from cancer were included in our study (mean age 6.3 ± 0.3 years). Complications occurred in about one fourth of all patients. Catheter-related blood stream infections (BSI) (n = 40, 36.4%) were most prevalent, but catheter tip position or vessel insertion site had no impact on the risk of infections. Dislodgement (n = 27, 24.6%) and occlusion (n = 11, 10.0%) were more frequent in “high” positioned catheter tips.While there was one patient who developed arrhythmia, no case of cardiac perforation, and in particular, no catheter-related death was recorded in our series. The vessel insertion site seemed to have no influence on the complication frequency of CAVDs.ConclusionThe catheter tip position seems to have an impact on the catheter-related complication profile in children. To avoid complications, we recommend avoiding a “high” localization of the catheter tip above the right main bronchus. “Low” catheter tip placement was associated with the lowest dislocation rate.Given the overall low complication rate, insertion and use of CVADs in children can generally be considered as safe.     

Effect of Dose Ratio on Mitoxantrone and Daunorubicin in Acute Myeloid Leukemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials

PurposeTo investigate the effects of mitoxantrone and daunorubicin in induced chemotherapy on complete remission (CR), death during induction therapy, overall survival (OS), disease-free survival (DFS), and relapse in patients of all ages with acute myeloid leukemia (AML).MethodsWe searched published reports at the Medline, Embase, and Cochrane Databases as well as other databases from inception through July 2019. There was no restriction on date of publication or language (PROSPERO registration CRD42018095843).ResultsWe enrolled 12 randomized controlled trials that included data of 4583 AML patients whose disease was untreated or relapsed/refractory, and compared the CR, death during induction therapy, DFS, and OS between mitoxantrone and daunorubicin. Mitoxantrone significantly increased the CR rate (relative risk = 1.07; 95% confidence interval [CI], 1.01, 1.14; P = .03) and DFS (hazard ratio = 0.87; 95% CI, 0.79, 0.96; P = .005) compared to daunorubicin. However, there was no significant difference in death during induction therapy (relative risk = 1.00; 95% CI, 0.81, 1.24; P = .99) and OS (hazard ratio = 0.94; 95% CI, 0.87, 1.01; P = .077) between the two drugs.ConclusionAlthough more studies are needed to compare mitoxantrone with higher-dose daunorubicin, the results showed that compared to daunorubicin, mitoxantrone can significantly improve CR and DFS in patients of all ages. These findings suggest that mitoxantrone may be a better choice than daunorubicin as an induction chemotherapy agent for AML patients, especially in developing countries.     

Blinatumomab or Inotuzumab Ozogamicin as Bridge to Allogeneic Stem Cell Transplantation for Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis

BackgroundBlinatumomab and inotuzumab ozogamicin are now widely used to treat relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).Patients and MethodsWe have reported the clinical course of 34 adult patients with r/r B-ALL receiving blinatumomab or inotuzumab ozogamicin at our institution from 2009 to 2019.ResultsBlinatumomab-based salvage therapy was applied for overt r/r B-ALL (n = 13) or minimal residual disease (MRD) positivity (n = 5). Of the 13 patients with r/r B-ALL, 9 (69%; 95% confidence interval [CI], 39%-91%) achieved complete remission (CR), with 78% of CR patients (95% CI, 40%-97%) reaching MRD negativity. MRD negativity was also achieved in all 5 patients treated for MRD positivity. The 1-year overall survival of patients receiving blinatumomab for r/r B-ALL and MRD positivity was 54% (n = 13; 95% CI, 26%-81%) and 80% (n = 5; 95% CI, 44-100), respectively. In the inotuzumab ozogamicin group, all 16 patients were treated for overt r/r B-ALL. The rate of CR was 94% (95% CI, 70%-100%), with 67% (95% CI, 38%-88%) of CR patients reaching MRD negativity. The 1-year OS after the first application of inotuzumab ozogamicin was 46% (95% CI, 18%-74%). Of those patients receiving blinatumomab and inotuzumab ozogamicin as a bridge-to-transplant strategy, 79% and 80%, respectively, proceeded to allogeneic stem cell transplantation. The most frequent drug-specific adverse events were similar to those previously reported, including cytokine release syndrome, capillary leak syndrome, and neurotoxicity for blinatumomab and transplant-associated veno-occlusive disease of the liver for inotuzumab ozogamicin.ConclusionTogether with previous observations from phase III clinical trials, these data suggest that blinatumomab and inotuzumab ozogamicin are highly effective salvage regimens in r/r B-ALL.     

Retrospective Analysis of Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia Treated with FLAG at a Comprehensive Cancer Center

BackgroundFLAG ± Ida (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), is a salvage chemotherapy regimen for relapsed or refractory (R/R) acute myeloid leukemia (AML), with complete remission (CR) rates historically ranging from 52% to 63%. We review the outcomes for patients with R/R AML treated with FLAG ± Ida at the University of California Davis Comprehensive Cancer Center.Patients and MethodsAdult patients (≥ 18 years) with R/R AML who received FLAG or FLAG + Ida from January 1, 2012 to October 31, 2016 were identified via chart review. Outcomes evaluated were CR, CR with incomplete hematologic recovery (CRi), overall response rate, overall survival (OS), relapse-free survival, and adverse events.ResultsForty-two patients were included. The median age was 52 years (range, 23-73 years), and 57% were male. Sixteen (38.1%) patients had relapsed disease, and 26 (61.9%) had refractory disease. Most (n = 35; 83.3%) patients had European LeukemiaNet intermediate-risk AML. Responses were CR in 20 (47.6%) and CRi in 6 (14.3%). The median OS was 10 months (range, 0.8-51 months), and the median relapse-free survival was 12 months (range, 1-51 months) for responders. The median OS for patients who achieved CR was not reached, and the estimated 48-month survival rate was 56%. The median OS after CRi or no response was 3.47 and 2.17 months, respectively. The median OS was not significantly different when censored for stem cell transplant following chemotherapy, nor with use/deferral of idarubicin. The most common adverse effects were pancytopenia and infection.ConclusionPatient outcomes after treatment with FLAG ± Ida for R/R AML remain similar to prior reports, confirming its role as a salvage regimen for these patients.     

A multimodal prehabilitation program in high-risk patients undergoing elective resection for colorectal cancer: A retrospective cohort study

AimUp to 50% of the patients experience complications after colorectal cancer (CRC) surgery. Improved preoperative physical and nutritional status can enhance clinical outcomes and reduce postoperative complications. This retrospective, single-center, observational cohort study assessed the impact of a four-week multimodal prehabilitation program on postoperative complications, unplanned readmissions, length of stay, and mortality in elective high-risk CRC patients.MethodElective high-risk CRC patients, defined as ASA ≥3 or ≥65yr, who attended the multimodal prehabilitation program (prehabilitation-group) were compared to a historical cohort receiving standard care (control-group). Differences in outcomes between these groups were tested using Fisher's Exact and Mann-Whitney U test. To adjust for confounding, multivariate logistic regression analysis was performed. The main study outcome was the occurrence of postoperative complications. Secondary outcomes included unplanned readmissions, length of hospital stay, and mortality.Results351 patients were included (n = 275 control-group, n = 76 prehabilitation-group). The complication rate was lower in the prehabilitation group compared to the control group, 26.3% (n = 20) versus 40% (n = 110) (p = .032). There were fewer unplanned readmissions in the prehabilitation group compared to the control group, 5.3% (n = 4) versus 16.4% (n = 45), p = .014. Median hospital days of stay was 1 day shorter for the prehabilitation-group (p = .004), mortality did not significantly differ between the groups.ConclusionThis study shows that the used multimodal prehabilitation program leads to a reduction of medical postoperative complications, unplanned readmissions, and shortens the median hospital stay compared with standard care in high-risk CRC patients undergoing elective CRC surgery.     

Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies

BackgroundThe Proviral Integration site of Moloney murine leukemia virus (PIM) kinases are implicated in tumorigenesis; the pan-PIM kinase inhibitor, INCB053914, demonstrated antitumor activity in hematologic malignancy preclinical models.Patients and MethodsThis phase 1/2 study evaluated oral INCB053914 alone or combined with standard-of-care agents for advanced hematologic malignancies (NCT02587598). In Parts 1/2 (monotherapy), patients (≥18 years) had acute leukemia, high-risk myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasm, myelofibrosis (MF), multiple myeloma, or lymphoproliferative neoplasms. In Parts 3/4 (combination therapy), patients had relapsed/refractory or newly diagnosed (≥65 years, unfit for intensive chemotherapy) acute myeloid leukemia (AML) or MF with suboptimal ruxolitinib response.ResultsParts 1/2 (n = 58): 6 patients experienced dose-limiting toxicities (DLTs), most commonly aspartate aminotransferase/alanine aminotransferase-elevated (AST/ALT; each n = 4). Fifty-seven patients (98.3%) had treatment-emergent adverse events (TEAEs), most commonly ALT-elevated and fatigue (36.2% each); 48 (82.8%) had grade ≥3 TEAEs, most commonly anemia (31.0%); 8 (13.8%) had grade ≥3 ALT/AST-elevated TEAEs. Parts 3/4 (n = 39): for INCB053914 + cytarabine (AML; n = 6), 2 patients experienced DLTs (grade 3 maculopapular rash, n = 1; grade 3 ALT-elevated and grade 4 hypophosphatemia, n = 1); for INCB053914 + azacitidine (AML; n = 16), 1 patient experienced a DLT (grade 3 maculopapular rash). Two complete responses were observed (1 with incomplete count recovery). For INCB053914 + ruxolitinib (MF; n = 17), no DLTs occurred; 3 patients achieved best reduction of >25% spleen volume at week 12 or 24.ConclusionINCB053914 was generally well tolerated as monotherapy and in combinations; TEAEs were most commonly ALT/AST-elevated. Limited responses were observed with combinations. Future studies are needed to identify rational, effective combination strategies.     

The Role of Hypertension and Renin-angiotensin-aldosterone System Inhibitors in Bleomycin-induced Lung Injury

IntroductionThe risk factors for bleomycin-induced lung injury (BLI), a fatal complication of cancer chemotherapy, are not well-established. The renin-angiotensin-aldosterone system (RAAS) has recently been suggested to play a role in the development of lung injury. This study clarified the impact of hypertension (HTN) and the administration of RAAS inhibitors on BLI occurrence in patients treated with bleomycin-containing regimens.Patients and MethodsWe retrospectively analyzed the data of 190 patients treated with a bleomycin-containing regimen for Hodgkin lymphoma or germ cell tumors at our institutions from 2004 to 2018.ResultsOverall, 190 patients received bleomycin, and symptomatic BLI occurred in 21 (11.1%) cases. In the multivariate analysis, age ≥ 65 years (odd ratio, 10.90; 95% confidence interval, 3.72-32.20; P < .001) and history of HTN (odds ratio, 3.32; 95% confidence interval, 1.07-10.30; P = .04) were found to be significant risk factors for BLI onset. BLI occurred in 3.6% (n = 5) of patients with no risk, 11.8% (n = 2) of those whose only risk factor was HTN, 31.6% (n = 6) of those whose only risk factor was age ≥ 65 years, and 57.1% (n = 8) of those with both risk factors (P < .001). BLI-induced mortality rates in each group were 0.0% (n = 0), 5.9% (n = 1), 10.5% (n = 2), and 42.9% (n = 6) (P < .001), respectively. Among 31 patients with HTN, BLI incidence was 12.5% in patients who were administered RAAS inhibitors and 53.3% in those who were not (P = .02).ConclusionOlder age and history of HTN were independent risk factors for the development of BLI, and the administration of RAAS inhibitors might reduce the onset of BLI.     

Limited Utility of Surveillance Imaging for Detecting Disease Relapse in Patients With Non-Hodgkin Lymphoma in First Complete Remission

IntroductionSurveillance imaging with computed tomography (CT) or positron emission tomography with CT (PET/CT) is commonly used in practice in patients with non-Hodgkin lymphoma (NHL) who are in remission after front-line therapies. We aimed to determine the utility of routine imaging for detecting first relapse in patients with NHL in complete remission (CR) after first-line therapies.Patients and MethodsWe retrospectively analyzed patients with NHL who achieved CR after first-line therapies and then subsequently had disease relapse. We evaluated whether the relapse was detected solely by surveillance CT or PET/CT or by patient-reported symptoms or physical examination findings, or both. Subgroup analysis was performed on baseline histologic type (indolent vs. aggressive NHL). Data were also collected to determine the cost of surveillance PET/CT and the number of additional diagnostic imaging procedures, invasive procedures, and iatrogenic complications directly resulting from an abnormality detected on a surveillance scan.ResultsOne hundred sixty-three patients with first relapse of NHL between January 1, 2000 and December 31, 2010 were included. The majority of the relapses were detected by patient-reported symptoms or physical examination, or both, as opposed to surveillance imaging (77.9% [n = 127] vs. 22.1% [n = 36]; P < .0001). There was no overall survival difference between the 2 groups (P = .66). Patient-reported symptoms led to the detection of the majority of relapses in aggressive (85.7% [n = 72] vs. 14.3% [n = 12]; P < .0001) as well as indolent NHL (69.6% [n = 55] vs. 30.4% [n = 24]; P = .0007). Surveillance PET/CT contributed to more than 75% of follow-up health care costs in the first 2 years of monitoring for relapse. The surveillance imaging group had 1 reported case of iatrogenic pneumothorax.ConclusionOur retrospective analysis suggests that there is a limited role for surveillance imaging by CT or PET/CT in detecting first relapse in NHL. There was no difference in survival outcomes between the 2 groups in our study.     

Acute Complications and Survival Analysis of Childhood Acute Lymphoblastic Leukemia: A 15-year Experience

BackgroundWe evaluated the acute complications that occurred during the treatment of childhood acute lymphoblastic leukemia (ALL) and documented the survival rates of children with ALL.Materials and MethodsWe retrospectively evaluated 110 children with a diagnosis of ALL treated with the Children’s Oncology Group protocol from 1999 to 2014. The demographic, clinical, and laboratory data of 110 patients and acute complications of eligible and evaluable 105 patients were recorded.ResultsOf the 110 patients, 65 were male and 45 were female. The mean age at admission was 8.3 ± 5.2 years. Ninety-seven patients (88.2%) had been diagnosed with pre–B-cell ALL, 11 (10%) with T-cell ALL, 1 (0.9%) with mixed phenotype acute leukemia, and 1 (0.9%) with mature B-cell acute leukemia. Of the 110 patients, 40 (36.3%) were in the standard-risk group and 70 (63.7%) were in high-risk group. Of the 110 patients, 105 had been followed up regularly and evaluated for acute complications. Infection was the most common complication (n = 93; 88.5%), followed by gastrointestinal (n = 29; 27.6%), neurologic (n = 28; 26.6%), metabolic/endocrine (n = 16; 15.2%), drug-related hypersensitivity (n = 16; 15.2%), avascular necrosis (n = 13; 12.3%), thrombotic (n = 11; 10.4%), severe psychiatric (n = 2; 1.9%), and various other (n = 12; 11.4%) complications. Of the 110 patients, 98 were assessed in terms of survival analysis. The 5- and 10-year overall survival rates were both 85.9% (standard error [SE], 3.6%). The relapse-free survival rates at 1, 3, and 5 years were 97.9% (SE, 1.5%), 91.3% (SE, 3%), and 86.3% (SE, 3.7%), respectively.ConclusionChildhood ALL, although categorized as curable malignancy owing to the improvements in treatment strategies in recent years, can cause acute complications affecting various systems. Thus, patients should be treated and followed up by multidisciplinary medical teams with high expertise.     

Upfront Autologous Stem Cell Transplantation for Untreated High-Risk Diffuse Large B-Cell Lymphoma in Patients Up to 60 Years of Age

BackgroundAlthough rituximab added to CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) is the standard chemotherapy for untreated DLBCL, its therapeutic effect is limited in younger patients with high-intermediate risk or high-risk disease according to the age-adjusted international prognostic index. In fact, the efficacy and safety of HDT plus rituximab followed by ASCT for such patients remain unclear.Patients and MethodsWe retrospectively investigated the safety and effectiveness of HDT/ASCT in patients with untreated DLBCL. Twenty-two patients, aged 60 years and younger, with untreated DLBCL (classified as high-intermediate [n = 14 (64%)] or high [n = 8 (32%)] risk) underwent upfront HDT/ASCT between January 2004 and December 2008, achieving either a complete response (CR; n = 15 (68%)) or a partial response (PR; n = 7 (32%)).ResultsThe 5-year overall survival rate was 81.0% and the progression-free survival rate was 73.0%, with no significant difference between risk groups based on the international prognostic index. The most common nonhematologic toxicity was febrile neutropenia [n = 9 (41%)]. The cause of all 3 fatalities was exacerbation of the underlying disease, and no treatment-related mortality was observed. No variables with a significant influence on overall survival were identified, but a correlation of the treatment response before transplanation with progression-free survival was suggested (CR vs. PR: 92% vs. 30%, P = .002).ConclusionThese results suggest that adding rituximab to upfront HDT/ASCT is feasible and can improve the outcome in untreated patients with poor-prognosis DLBCL. In the future, upfront HDT/ASCT should be more extensively evaluated in clinical trials.     

AML in Saudi Arabia: Analysis According to the European LeukaemiaNet 2017 Cytogenetic Classification

IntroductionTo the best of our knowledge, few studies have addressed the prognosis of patients with acute myeloid leukemia (AML) in Saudi Arabia. The present study retrospectively analyzed the prognostic factors in patients with de novo AML at a single institution owing to the observation of some differences with the reported data from the Western world.Patients and MethodsPatients with de novo AML who had been referred to King Abdulla Medical City were included. All patients had undergone bone marrow aspiration, biopsy, flow cytometry, cytogenetics (conventional and fluorescence in situ hybridization panel performed at Mayo Clinic), molecular tests, and other routine tests.ResultsThe data from 170 patients were reviewed. Of the 170 patients, 26 had had acute promyelocytic leukemia, 16 with AML had received less intensive therapy, 119 had received intensive induction, and 8 had refused treatment. The present analysis was limited to the 119 patients who had received intensive induction therapy. For the major cytogenetic categories, 17 of 27 patients with core binding factor leukemia (62.9%) were reassigned to the intermediate (n = 10; 37%) or unfavorable (n = 7; 25.9%) risk group according to the FLT3-ITD and NPM results. Of the 50 cases of normal cytogenetic findings, 2 (4%) were considered unfavorable, 12 (24%), favorable, 30 intermediate (60%), and 6 (12%) unknown. The median leukemia-free survival was 21.5 months. The median overall survival was 16.4 ± 2.2 months, with a 3-year survival rate of 37.2%. Multivariate Cox regression analysis revealed that the cytogenetics results (P = .002) and the presence of FLT-3 (P = .03) were independent prognostic factors for relapse-free survival. Performance status, response, relapse, and cytogenetics findings were independent prognostic factors for survival.ConclusionsThe results from the present study revealed some differences in patient age and cytogenetic risk groups for patients with AML in our region and those in the Western world, including a younger median age, relevance of core binding factor leukemia, and a greater incidence of monosomies.     

Retrospective Analysis of Prognostic Factors Associated With Response and Overall Survival by Baseline Marrow Blast Percentage in Patients With Myelodysplastic Syndromes Treated With Decitabine

BackgroundAfter the World Health Organization (WHO) changed the definition of acute myeloid leukemia (AML) to ≥ 20% blasts, the International Working Group (IWG) response criteria for myelodysplasia were updated. This retrospective analysis evaluated response to decitabine using updated IWG criteria in patients pooled from 2 decitabine trials.Patients and MethodsOutcomes for patients with myelodysplastic syndrome (MDS) with baseline marrow blasts ≥ 20% and < 30% (RAEB-t group) and < 20% (MDS group) were compared.ResultsPatients with RAEB-t (n = 26) had a significantly shorter time from diagnosis to study treatment (7.3 vs. 18.3 months), a higher International Prognostic Scoring System (IPSS) risk (77% vs. 16% high-risk patients), and lower median baseline platelet count (62.3 vs. 112.7 × 10³/μL) vs. patients with MDS (n = 157), yet no significant difference in overall response rate (ORR) (15.4% vs. 28.0%). Patients with MDS had better duration of response (9.9 vs. 5 months; P = .024) and overall survival (OS) (16.6 vs. 9.0 months; P = .021) compared with patients with RAEB-t.ConclusionDecitabine is active in and may benefit patients with > 20% blasts (RAEB-t).     

Effect of NPM1 and FLT3 Mutations on the Outcomes of Elderly Patients With Acute Myeloid Leukemia Receiving Standard Chemotherapy

BackgroundThe effect of prognostically important gene mutations (MUTs), nucleophosmin (nucleolar phosphoprotein B23, numatrin) (NPM1) and fms-related tyrosine kinase 3 (FLT3), in elderly patients with acute myeloid leukemia (AML) is not well defined.Patients and MethodsWe analyzed 557 patients, 65 years of age or older with newly diagnosed AML, treated at our institution between 2000 and 2010 with cytotoxic chemotherapy. NPM1 and FLT3 analysis were available in 146 patients (26%) and 388 patients (70%), respectively.ResultsNPM1 and FLT3 MUTs occurred in 16% and 12% of patients, respectively. No difference in median overall survival was observed between FLT3-MUT and NPM1-MUT patients who received cytotoxic chemotherapy. Outcome was significantly better among patients with NPM1-MUT/FLT3-wild type (WT) genotype (n = 14) compared with patients carrying FLT3/NPM1 genotypes other than NPM1-MUT/FLT3-WT (n = 125). The complete remission rates were 71% and 49%, respectively (P = .11). The median survival was 21.5 months vs. 9.0 months and estimated 2-year survival rates were 51% vs. 38%, respectively (P = .003). NPM1 and FLT3 MUTs appear to occur less frequently in elderly AML patients. The prognostic effect of isolated NPM1- or isolated FLT3-MUT is minimal.ConclusionElderly AML patients with NPM1-MUT/FLT3-WT genotype have significantly improved outcomes compared with patients with other NPM1/FLT3 genotypes when treated with cytotoxic chemotherapy.     

Comparison of Azacitidine and Decitabine in Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Network Meta-analysis

BackgroundMyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have a poor prognosis. Azacitidine (AZA) and decitabine (DAC) are the most widely used hypomethylating agents. However, few randomized controlled trials (RCTs) have compared AZA and DAC head to head in MDS or AML. This study intended to conduct a network meta-analysis to compare the 2 drugs to provide more guidance using evidence-based medicine.Patients and MethodsA comprehensive search for RCTs was performed till July 31, 2020. The network meta-analysis was conducted using the Markov chain Monte Carlo method. The primary endpoints were overall survival (OS) and the incidence of adverse events, and the secondary endpoints were complete remission (CR) rate, overall remission rate (ORR), and AML-free survival. There were 6 RCTs with 1072 MDS patients, and 3 RCTs with 1256 AML patients.ResultsIn MDS, AZA showed better AML-free survival (hazard ratio = 0.62; 95% CI, 0.43-0.9), whereas DAC had the possibility of achieving better CR and ORR, and AZA had the possibility of obtaining better OS with lower toxicity. As for elderly AML patients, DAC had the possibility of achieving superior CR, ORR, and OS, while the toxicity was relatively higher. Furthermore, subgroup analysis for patients ≥ 75 years old or of high risk in MDS suggested that AZA achieved better OS.ConclusionFor MDS, especially patients with intermediate or high risk disease with advanced age and poor general condition, AZA may be a better choice, while DAC may be of more benefit in elderly AML patients.     

Impact of Blood Count Recovery-based Complete Remission Before Allogeneic Hematopoietic Stem Cell Transplantation on Survival in Patients With Acute Myeloid Leukemia

BackgroundPatients who achieve complete remission (CR) with incomplete blood count recovery (CRi) in acute myeloid leukemia (AML) have inferior overall survival and lower progression-free survival. The aim of this study was to define whether blood count recovery-based CR before allogeneic hematopoietic stem cell transplantation (alloHSCT) had an impact on survival in patients with AML.Materials and MethodsThis study has been performed in a retrospective manner. One hundred one patients with AML who received an alloHSCT in our transplant center at Hacettepe University Hospital between the years 2001 and 2018 were evaluated. CRi were defined as bone marrow CR with absolute neutrophil count < 1000/mm³ and/or platelet count < 100.000/mm³. CR and CRi were confirmed just before alloHSCT in bone marrow and peripheral blood, respectively.ResultsA total of 101 patients were entered into the study between 2001 and 2018. Median follow-up for all survivors was 38 months (range, 6-220 months). The 5-year overall survival for patients who were in CRi and patients who were in CR before transplantation were 58% and 67%, respectively (P = .68). The 5-year progression-free survival for patients who were in CRi and patients who were in CR before transplantation were 68% and 64%, respectively (P = .99).ConclusionIn conclusion, we observed equivalent posttransplant outcomes between patients who were in CR and patients who were in CRi before alloHSCT. We assume that alloHSCT eliminated the negative effect of pre-transplant blood count levels.