Pediatric Hematological Malignancies - Clinical Manifestation, Treatment and Follow-Up

Author(s):  
Naga Ramya Lanka ◽  
Krishna Kanth Pulicherla
2021 ◽  
Author(s):  
Carlo Zaninetti ◽  
Martina Wolff ◽  
Andreas Greinacher

AbstractInherited platelet disorders (IPDs) are a group of rare conditions featured by reduced circulating platelets and/or impaired platelet function causing variable bleeding tendency. Additional hematological or non hematological features, which can be congenital or acquired, distinctively mark the clinical picture of a subgroup of patients. Recognizing an IPD is challenging, and diagnostic delay or mistakes are frequent. Despite the increasing availability of next-generation sequencing, a careful phenotyping of suspected patients—concerning the general clinical features, platelet morphology, and function—is still demanded. The cornerstones of IPD diagnosis are clinical evaluation, laboratory characterization, and genetic testing. Achieving a diagnosis of IPD is desirable for several reasons, including the possibility of tailored therapeutic strategies and individual follow-up programs. However, detailed investigations can also open complex scenarios raising ethical issues in case of IPDs predisposing to hematological malignancies. This review offers an overview of IPD diagnostic workup, from the interview with the proband to the molecular confirmation of the suspected disorder. The main implications of an IPD diagnosis are also discussed.


2010 ◽  
Vol 67 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Nebojsa Mujovic ◽  
Miodrag Grujic ◽  
Stevan Mrdja ◽  
Aleksandar Kocijancic ◽  
Tatjana Potpara ◽  
...  

Background/Aim. The occurrence of atrial fibrillation (AF) in the presence of an accessory pathway (AP) that conducts rapidly is potentially lethal because the rapid ventricular response may lead to ventricular fibrillation (VF). The aim of the study was to determine long-term efficacy of AP catheter-ablation using radiofrequency (RF) current in secondary prevention of VF in WPW patients. Methods. Study included a total of 192 symptomatic WPW patients who underwent RF catheter-ablation of AP in our institution from 1994 to 2007 and were available for clinical follow-up for more than 3 months after procedure. Results. Before ablation, VF was recorded in total of 27 patients (14.1%). In 14 of patients (51.9%) VF was the first clinical manifestation of WPW syndrome. A total of 35 VF episodes were identified in 27 patients. The occurrence of VF was preceded by physical activity or emotional stress in 17.1% of cases, by alcohol abuse in 2.9% and by inappropriate intravenous drug administration in 28.6%. In addition, no clear precipitating factor was identified in 40% of VF cases, while informations about activities preceding 11.4% of VF episodes were not available. The follow-up of 5.7 ? 3.3 years was obtained in all of 27 VF patients. Of the 20 patients who underwent successful AP ablation, all were alive, without syncope or ventricular tachyarrhythmias during long-term follow-up. In 4 of 7 unsuccessfully treated patients, recurrence of supraventricular tachycardia and/or preexcited atrial fibrillation were recorded; one of these patients suddenly died of VF, 6 years after procedure. Conclusion. In significant proportion of WPW patients, VF was the first clinical manifestation of WPW syndrome, often precipitated by physical activity, emotional stress or inappropriate drug administration. Successful elimination of AP by percutaneous RF catheter-ablation is highly effective in secondary prevention of life-threatening tachyarrhythmias in patients with ventricular preexcitation.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Osamu Imataki ◽  
Hiroyuki Kubo ◽  
Akihiro Takeuchi ◽  
Makiko Uemura ◽  
Norimitsu Kadowaki

Abstract Background Clonal chromosomal alterations (CCAs) reflect recurrent genetic changes derived from a single evolving clone, whereas nonclonal chromosomal alterations (NCCAs) comprise a single or nonrecurrent chromosomal abnormality. CCAs and NCCAs in hematopoietic cells have been partially investigated in cytopenic patients without hematological malignancies. Methods This single-center retrospective study included 253 consecutive patients who underwent bone marrow aspiration to determine the cause of cytopenia between 2012 and 2015. Patients with hematological malignancies were excluded. CCA was defined as a chromosomal aberration detected in more than two cells, and NCCA was defined as a chromosomal aberration detected in a single cell. Results The median age of the patients was 66 years. There were 135 patients without hematological malignancies (median age, 64 years; 69 females); of these, 27 patients (median age, 69 years; 8 females) harbored chromosomal abnormalities. CCAs were detected in 14 patients; the most common CCA was −Y in eight patients, followed by inv.(9) in three patients and mar1+, inv. (12), and t (19;21) in one patient each. NCCAs were detected in 13 patients; the most frequent NCCA was +Y in four patients, followed by del (20), + 8, inv. (2), − 8, and add (6) in one patient each. Moreover, nonclonal translocation abnormalities, including t (9;14), t (14;16), and t (13;21), were observed in three patients. One patient had a complex karyotype in a single cell. The remaining 106 patients with normal karyotypes comprised the control group (median age, 65 years; range, 1–92 years; 56 females). Further, follow-up analysis revealed that the overall survival of the NCCA group was worse than that of the CCA and the normal karyotype groups (P < 0.0001; log-rank test). The survival of the NCCA-harboring cytopenic patients was worse than that of the CCA-harboring cytopenic patients without hematological malignancies, suggesting that follow-up should be considered for both CCA- and NCCA-harboring cytopenic patients.


2019 ◽  
Vol 9 (10) ◽  
Author(s):  
Vivek Kumar ◽  
Sikander Ailawadhi ◽  
Leyla Bojanini ◽  
Aditya Mehta ◽  
Suman Biswas ◽  
...  

Abstract With improving survivorship in chronic lymphocytic leukemia (CLL), the risk of second primary malignancies (SPMs) has not been systematically addressed. Differences in risk for SPMs among CLL survivors from the Surveillance, Epidemiology, and End Results (SEER) database (1973–2015) were compared to risk of individual malignancies expected in the general population. In ~270,000 person-year follow-up, 6487 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI:1.17–1.23). The higher risk was for both solid (SIR 1.15; 95% CI:1.12–1.18) and hematological malignancies (SIR 1.61; 95% CI:1.5–1.73). The highest risk for SPMs was noted between 2 and 5 months after CLL diagnosis (SIR 1.57; 95% CI:1.41–1.74) and for CLL patients between 50- and 79-years-old. There was a significant increase in SPMs in years 2003–2015 (SIR 1.36; 95% CI:1.3–1.42) as compared to 1973–1982 (SIR 1.19; 95% CI:1.12–1.26). The risk of SPMs was higher in CLL patients who had received prior chemotherapy (SIR 1.38 95% CI:1.31–1.44) as compared to those untreated/treatment status unknown (SIR 1.16, 95% CI:1.13–1.19, p < 0.001). In a multivariate analysis, the hazard of developing SPMs was higher among men, post-chemotherapy, recent years of diagnosis, advanced age, and non-Whites. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL.


2016 ◽  
Vol 150 (1) ◽  
pp. 35-39
Author(s):  
Şule Altıner ◽  
Nüket Y. Kutlay ◽  
Osman İlhan

Constitutional trisomy 8 mosaicism (CT8M) is a rare chromosomal abnormality. The phenotype varies from normal features to severe malformations. CT8M increases the risk of developing leukemia and myelodysplastic syndrome. As CT8M is very rare, its diagnosis can easily be overlooked, especially in cases with mild phenotypes. Here, we report the diagnostic process of a 40-year-old female patient with CT8M and discuss the importance of follow-up in monitoring for hematological malignancies.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5285-5285
Author(s):  
Christelle Ferra ◽  
Maite Misis ◽  
Albert Oriol ◽  
Pilar Marcos ◽  
Natalia Lloveras ◽  
...  

Abstract When patients with hematological malignancies develop a life-threatening complication there may be reluctance to admit them in intensive care units (ICU) because of their supposed poor prognosis. The objective of this study was to evaluate the mortality during the ICU admission, the long-term survival, and the prognostic factors that contribute to the survival of patients with hematological malignancies who were transferred to ICU due to a life-threatening complication. From January 2000 to May 2004, the variables at admission and during stay at the ICU, and the follow-up were reviwed in 58 consecutive critically-ill patients with a hematological malignancy from a single institution. The median age (range) was 55 (15–75) years and the male/female ratio was: 38/20. The hematological underlying diseases were: NHL (18 patients), AML (10), ALL (9), MM (6), chronic lymphoproliferative disorder (5), chronic myeloproliferative disorder (4), myelodysplastic syndrome (3), aplastic anemia (2) and Hodgkin’s lymphoma (1). Seven patients had received a hematopoietic stem cell transplant prior to the ICU admission. The main life-threatening acute illness precipitating the ICU transfer were: septic shock (26 patients, 45%), respiratory failure (21, 36%), non-septic hemodynamic instability (5, 9%), respiratory arrest related to a neurological event (2, 3%), post-surgical status (2, 3%), cardiac infarction (1, 2%) and polytrauma (1, 2%). Twenty-one patients (36%) could be discharged alive from the ICU. The median overall survival (range) for ICU discharged patients was 23 (0–54) months, with a median follow-up of 8 months. The actuarial probability of discharged patients to be alive was 56% (CI 95%: 31–75) at 6 months, and a 48% (CI 95%: 13–70) at 12 months. The mean Acute Physiology and Chronic Health Evaluation II (APACHE) score at admission, neutropenia, need for mechanical ventilation, maximum FIO2 requirements at 24 hours from admission, presence of septic shock, renal impairment or liver damage, were associated with a poor outcome in the univariate analysis. A documented infection was not associated with a higher mortality rate except for fungal infection. The APACHE II score at 48 and 72 hours of ICU admission decreased both in surviving and non-surviving patients due to therapeutic manoeuvres and was not predictive of the outcome. The type of the hematological malignancy, its prognosis and the presence of active disease at ICU admission did not predict patients outcome in our series. The number of failing organs also predicted a poorer survival for patients with more than two failing organs (p=0.038). In a multivariate logistical regression model, only the cardiovascular failure requiring vasoactive and the need of mechanical ventilation predicted outcome in the ICU admitted patients diagnosed with a hematological malignancy. A high proportion of admitted patients with a life-threatening complication and a hematological malignancy could be discharged from ICU. Although the mortality rate immediately after ICU discharge was high, those patients that survived the first week outside ICU had an expected survival only conditioned by their hematological malignancy.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5290-5290
Author(s):  
Tiziano Barbui ◽  
Marilena Romero ◽  
Federica Delaini ◽  
Elisa Sasso ◽  
Gianni Tognoni ◽  
...  

Abstract The expected effects of rHuEPO treatments on the quality of life of patients exposed to chemotherapeutic regimens have favored its widespread clinical utilization, even in the absence of a solid consensus on the criteria for assuring an optimal cost-effectiveness and safety profile. A prospective multicenter outcomes-oriented observational protocol adopted by a network of 29 hematological centers has explored specifically the relationship between the yield of rHuEPO, therapy and the levels of endogenous EPO in a cohort of 478 consecutively diagnosed patients (55% males), with NHL (43%), CLL (16%), MM (41%), in first (287, 60%) and successive (191, 40%) chemotherapy line. Over the 12 months follow-up, 4/252 and 32/226 patients with Hb > 11 g/dl and < 11 g/dl died; up to 20% of those with inadequate EPO levels did not receive rHuEPO, while 16/35 (46%) of those with adequate EPO levels were prescribed rHuEPO. At a multivariate analysis, only patients with baseline Hb levels between 10 and 11 g/dl and in first line chemotherapy regimen, but not those with levels < 10 g/dl or in > 1st. line therapy benefited from rHuEPO. Conclusions: While providing an informative epidemiological profile of the patients exposed to rHu EPO during chemotherapy and of the care they receive in the routine practice of specialized centers, the study documents some of the areas of uncertain practice, and confirms the need of prospective, controlled trials in the specific value of rHu EPO in well-characterized subpopulations on chemotherapy for hematological malignancies.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1895-1895
Author(s):  
Anuj Mahindra ◽  
Brian Bolwell ◽  
Brad Pohlman ◽  
Lisa Rybicki ◽  
Stacey Brown ◽  
...  

Abstract We compared the safety and effectiveness of high-dose etoposide followed by granulocyte colony-stimulating factor (G-CSF) to G-CSF alone for peripheral-blood progenitor cell (PBPC) mobilization regimen in patients with non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) who underwent autotransplantation (ASCT). Primary end points were CD 34+ cell collection, post-priming hospitalization for neutropenic fever and incidence of secondary malignancy. Prior studies have demonstrated that high dose etoposide significantly improves the proportion of patients who collect sufficient PBPC’s for transplantation. From 1/1993 through 12/2005, 352 patients received etoposide (2g/m2) followed by G-CSF (10mcg/kg/day) and 318 who received G-CSF (10mcg/kg/day) alone underwent ASCT. Patients who had inadequate cell collection were excluded. Mean age of patients receiving etoposide and G-CSF was 49 years and G-CSF alone was 45 years (p&lt;0.001). The two groups were otherwise similar with respect to bone marrow involvement, International Prognostic Index, number of prior chemotherapy regimens, prior radiation therapy and disease status at transplant. In the group receiving etoposide, 216 patients (61%) are alive with a median follow up of 34.9 months (range, 4.1–93.8). In the G-CSF group, 162 (51%) patients are alive with a median follow up of 85.5 months (range, 6.2–153.2). In the etoposide group, median total CD34+ cells collected were 9.14×106/kg with 41% of all patients having adequate (2×106 cells/kg) CD 34+ collection after 2 days of apheresis compared to a median CD34+ cells collected in the G-CSF group of 3.93×106/kg (range, 1.98–50.38) with only 16% patients having adequate collection after 2 days. Post-priming readmissions for neutropenic fever were required in 86 patients (24%) in the etoposide group, none of which were fatal, and 1 patient in the G-CSF alone group. Following transplantation, median length of stay, times to neutrophil engraftment and platelet recovery were similar in the two groups as were the incidence and causes of death within 100 days of transplantation. Secondary malignancies occurred in 14 patients (4%) in the etoposide group of whom 7 patients had hematological malignancies (MDS=4; AML = 2; ALL=1) and in 24 (7.5%) patients receiving G-CSF alone, with 14 patients having hematological malignancies (MDS=9; AML=3; CLL=1; HD=1). The estimated incidence of secondary malignancies at 5 years was 7.1% in the etoposide group and 7.8% in the G-CSF alone group as shown below: Figure Figure There was no significant difference in the incidence of secondary malignancies (p=0.73) or in the incidence of relapse (p=0.5) or survival (p=0.15) between the two groups. Conclusion: The present study shows that even when restricted to patients who collect adequate numbers of PBPCs, the addition of etoposide significantly improves the effectiveness of mobilization. This occurs at the cost of an increased incidence of neutropenic fever but with no mortalities. Following transplantation, there is no evidence of increased adverse effects due to addition of etoposide for priming, including on the incidence of secondary malignancies.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1171-1171
Author(s):  
Abraham S Kanate ◽  
Farhad Khimani ◽  
Aaron Cumpston ◽  
Kathy Watkins ◽  
Sonia Leadmon ◽  
...  

Abstract Abstract 1171 Poster Board I-193 Purpose: Peripheral blood allogeneic hematopoietic cell transplant (HCT) is used to treat various types of hematological malignancies. Current knowledge supports that increased CD34 + cell dose in the infusate is associated with earlier leukocyte recovery. The dose of CD3 +, CD4 + and CD8 + cells is largely disregarded except in T-cell depleted transplant. The correlation between various cell doses and outcomes is an area of great interest in HCT. Our analysis focuses on the impact of T-cell subset dosing, on outcomes after HCT, such as acute graft versus host disease (GVHD) and mortality. Methods: Retrospective analysis was conducted on 134 consecutive patients who underwent peripheral blood allogeneic HCT for various hematological malignancies in our institution between January 2003 and December 2008. Statistical analysis was performed using SPSS 15.0. The Chi - square test was used to determine any association between cell doses and the incidence of acute GVHD and all-cause mortality at one year of follow-up after transplant. Results were also compared with the association between CD3+ and CD8+ cell doses and incidence of acute GVHD as reported in 2007 by our institution. Results: A total of 134 patients were included in our analysis, consisting of 49 females and 85 males. The median age was 49 years (range 17-69). HCT was from matched related donors in 68 and from matched unrelated donors in 66 patients. A variety of conditioning regimens were used in preparation for the HCT. Overall survival at 1 year of follow-up was 60%, the incidence of acute GVHD was 52%, and chronic GVHD was 29%. All-cause mortality at one year follow up was found to be significantly higher when the CD3+ cell dose was < 30.5 × 107/kg IBW (49% vs. 29%, P = 0.018). All-cause mortality was also significantly increased when CD8+ cell dose was < 9.2 × 107/kg IBW (50% vs. 33%, P= 0.05). A CD8+ cell dose of < 9.2 × 107/kg IBW was also associated with an increased risk of grades 2-4 acute GVHD (48% vs. 22%, P = 0.026). There was no association of statistical significance between CD3+ and CD4+ cell doses and the incidence of acute GVHD. Conclusion: The data suggests a statistically significant inverse association between mortality and CD3+ cell dose of <30.5 × 107/kg IBW. A CD8+ cell dose of <9.2 × 107/kg IBW was also associated with increased all-cause mortality and acute GVHD (grades 2-4). Our institution reported in 2007, a significant association between the incidence of acute GVHD (grades 2-4) and CD3+ cell dose < 33.5 × 107/kg IBW and CD8+ cell dose of < 6.2 × 107/kg IBW, based on series of 66 patients. As we increased the sample size to 134, the association between CD3+ cell dose and acute GVHD was no more present. We conclude that T-cell dose is an important factor in terms of outcomes after all allogeneic HCT irrespective of preparative regimen. T-cell subsets likely play a pivotal role in transplant results, though it is not well described. Analysis of larger databases is required to substantiate our results. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4389-4389
Author(s):  
Oscar Gonzalez-Llano ◽  
Elias Eugenio Gonzalez-Lopez ◽  
Ana Carolina Ramirez-Cazares ◽  
Edson Rene Marcos-Ramirez ◽  
Guillermo J. Ruiz-Arguelles ◽  
...  

Abstract Patients with high-risk hematological malignancies have a poor prognosis without a hematopoietic stem cell transplant. An HLA- haploidentical donor is available in 95% of the cases, and post-transplant cyclophosphamide permits the use of T-cell replete grafts in settings were ex-vivo manipulation is not available. The experience with HLA-haploidentical HSCT with PBSC and post-tranplant Cy in the pediatric and adolescent population is limited; we report the following experience. We retrospectively collected data on 25 patients (0 to 21 years old) with hematological malignancies, who underwent ambulatory haploidentical HSCT with post-transplant Cy from November 2011 to November 2014. The different conditioning regimens are described in Table 1. All patients received high-dose Cy(50mg/kg) on days +3 and +4. Cyclosporine A (CYA; 6mg/kg/d per os) and mycophenolate mofetil (MMF; 15mg/kg two times daily per os) were started on day +5. MMF was discontinued on day +35 and tapering of cyclosporin started day +90 in the absence of GVHD. All patients received anti-microbial prophylaxis for bacteria, fungal, herpes infection and Pneumocystis jiroveci according to institutional practices. First chimerism was performed at day +30, and second chimerism at day +100. Primary graft failure was defined when neutrophil counts did not exceed 0.5 x 109/L by day +30. Acute and chronic GVHD were graded according to NIH criteria. Patient, donor and stem-cell harvest characteristics are described in Table 1. All patients had high risk hematological malignancies. There were 5 patients who underwent their first transplant on 1st CR, 4 with ALL with high risk cytogenetics and 1 with AML. All other patients were defined as high risk because they were refractory/relapsed. Twenty-three patients (92%) had neutrophil engraftment after a median 17 (7-24) days. Platelet engraftment was observed in 20 (80%) patients after a median of 14.5 (11-23) days, 3 (12%) patients did not have platelet counts below 20,000/mcL. One patient was catalogued as a primary failure for not achieving neutrophil and platelet engraftment by day +30. One patient died before engraftment at day +10 of septic shock. Four patients (16%) died before day +30. The only patient that did not have a complete chimerism, had a diagnosis of AML and 30% of donor cells by day +30, by day +45 relapse of disease was documented. After a median follow-up of 157 days, 13 patients (52%) remain alive, with an estimated 1-year OS of 52% (95%CI: 30.4 - 65.6%).Nine patients (36%) died of complications (mainly infectious) not related to relapse at a median time of 66 days (10-579 days) from stem cell infusion. Nine patients (36%) relapsed in a median time of 105 days (45-288 days); three of those patients died at days +150, +113 and + 370 from transplant. Estimated 1 year event-free survival is 40.2% (95%CI: 41.3 - 75.8%) (Figures 1 and 2). Patients transplanted on 1st CR had a median follow-up of 664 days with an OS and EFS of 80% (4 patients), which was statistically different from the rest of the population (p=0.03) (Figure 3). Among those who engrafted (n=21), 9 cases (42.9%) had grade 2-4 acute GVHD and 4 cases (19%) of grade 3-4 acute GVHD. Three patients (14.3%) developed chronic GVHD, two had mild skin or liver cGVHD. One patient had severe (NIH stage 3) skin cGVHD, she was alive and with a grade 2 cGVHD until last follow up at day +893. Outpatient procedure, HLA-haploidentical HSCT including PBSC as a stem cell source, and post-transplant T-cell in vivo depletion using high-dose cyclophosphamide is feasible in children and adolescents, with acceptable rates of response and GVHD. Table 1. Patient, donor and harvest characteristics Variable N=25 Age, median(range in years) 10 (1-21) Gender, n(%) Male Female 17 (68%) 8 (32%) Diagnosis, n(%) ALL-B ALL-T AML CML 16 (64%) 2 (8%) 5 (20%) 2 (8%) Time from diagnosis to transplant (months) 17.2 (1.9-153.5) Conditioning regimen, n(%) Cy 1500mg/m2 + Flu 75mg/m2 + Bu 9.6mg/kg (IV) Cy 1050mg/m2 + Flu 75mg/m2 + Bu 12 mg/kg (oral) Cy/VP-16/RT Cy/Flu/Mel 16 (64%) 6 (24%) 2 (8%) 1 (4%) Donor, n(%) Mother Father Sister 20 (80%) 3 (12%) 2 (8%) Donor age, median(range in years) 38 (17-49) Infused CD34+ x 106/kg, median(range) 11 (3.2-20) Disclosures No relevant conflicts of interest to declare.


Sign in / Sign up

Export Citation Format

Share Document