Extreme Tooth Abnormalities and Treatment under General Anesthesia in a Child with chronic GVHD Surviving Relapse of Acute Lymphoblastic Leukemia

2012 ◽  
Vol 37 (2) ◽  
pp. 199-201 ◽  
Author(s):  
S Maeda ◽  
M Suda ◽  
M Ishii ◽  
Y Tomoyasu ◽  
H Higuchi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
General Anesthesia ◽  
Dental Treatment ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Term Treatment ◽  
Permanent Teeth ◽  
Dental Abnormalities ◽  
Long Term Treatment ◽  
One Year

Treatment for acute lymphoblastic leukemia (ALL) mainly consists of chemotherapy, irradiation and bone marrow transplantation. In terms of long-term treatment effects, dental abnormalities and chronic graft-versus host disease (GVHD) are problems. We present a patient surviving relapse of ALL at one year of age. He had extreme dental abnormalities and multiple caries. Most of his permanent teeth were abnormal, and multiple caries were observed. Since he had a strong vomiting reaction to dental treatment, general anesthesia was given. During the general anesthesia, much sputum was aspirated because of chronic GVHD. His dental condition was worse than other cases reported previously. Since the survival rate has increased recently, the dental effects of ALL treatment have become significant. Especially, in patients undergoing total body irradiation at under 2 years of age, it is highly likely that dental problems will occur in the future.

Evaluation of Gonadal Function Following Long-Term Treatment for Acute Lymphoblastic Leukemia in Girls

1987 ◽  
Vol 9 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Titania Pasqualini ◽  
María Eugenia Escobar ◽  
Horacio Domené ◽  
Federico Sackmann Muriel ◽  
Santiago Pavlovsky ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Term Treatment ◽  
Gonadal Function ◽  
Long Term Treatment

Dental Development in Children After Chemotherapy

2017 ◽  
Vol 68 (6) ◽  
pp. 1397-1400
Author(s):  
Cristina Bica ◽  
Mihaela Chincesan ◽  
Daniela Esian ◽  
Krisztina Martha ◽  
Valentin Ion ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tooth Development ◽  
Lymphoblastic Leukemia ◽  
Treatment Method ◽  
Paediatric Oncology ◽  
Structural Defects ◽  
Dental Development ◽  
Cytostatic Agents ◽  
Dental Abnormalities ◽  
Tooth Buds

Chemotherapy, as a treatment method in paediatric oncology, coincides with the physiological process of tooth development. The interference between cytostatic agents and the cycle of the cells with specialised functions in the formation and mineralisation of dental structures leads to the appearance of abnormalities in the development of the tooth buds, structural defects and disorderly eruption. We have looked into the distribution of developmental tooth disorders in a group of children suffering from malignant ailments. The study reveals a high occurrence of microdontia and agenesis of premolars among children diagnosed with high-risk acute lymphoblastic leukemia at the age between 1 and 6, as well as tooth eruption disturbances in 70% of the children. The nature and the severity of dental abnormalities depend on the type of cytostatic medication, the dosage and the frequency of therapeutic cycles, the age of the child at the beginning of the oncological therapy, as well as on the stage of the odontogenesis.

Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide

1994 ◽  
Vol 131 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Josef Marek ◽  
Václav Hána ◽  
Michal Kršek ◽  
Vlasta Justová ◽  
France Catus ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Slow Release ◽  
Serum Levels ◽  
Term Treatment ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Long Term Treatment ◽  
Active Acromegaly ◽  
One Year

Marek J, Hána V. Kršek M. Justová V, Catus F, Thomas F. Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide. Eur J Endocrinol 1994;131:20–6. ISSN 0804–4643 Thirteen patients with active acromegaly despite previous surgery were treated with 30 mg lanreotide im twice a month for 9 months. In 10 subjects the treatment continued to 19 months. GH serum levels of all patients decreased significantly from an initial value of 32.0 (29.4) μg/l [median (standard error of median)] to 10.0 (3.6) and 19.1 (5.7) after 3 and 9 months of treatment, respectively. In the 10 patients with the treatment longer than one year the decrease in GH was from 46.8 (29.4) μg/l to 12.5 (5.0) and 16.1 (5.3) after 13 and 19 months, respectively. IGF-I serum levels decreased significantly from 1193 (73)μg/l to 782 (99) and 621 (103) after 3 and 9 months, respectively, and were normalized in 3 patients. In the 10 patients treated for longer than one year, levels decreased significantly from 1318 (74)μg/l to 653 (170) and 742 (180) after 13 and 19 months, respectively. IGF BP-3 levels were reduced to the normal range in 6 patients and decreased from 8.7 (1.5)mg/l to 6.4 (0.8) and to 5.4 (1.0) after 3 and 9 months, respectively. In the patients with the 19 months treatment the decrease was from 9.3 (1.6) mg/l to 3.9 (0.9) and 4.8 (0.9) after 13 and 19 months, respectively. The IGF BP-3 to IFG I ratio increased in 7 patients. This elevation significantly correlated with the decrease in bioassayable somatomedin. Prolactin serum levels fell in all patients with increased prolactin secretion. Testosterone plasma levels increased in 4 out of 5 men without replacement therapy. Clinical improvement was observed in all patients. A reduction of tumour mass was observed in five patients and complete disappearance of the tumour in one subject. All patients complained of mild abdominal pain and softened stools for several days following the injections. However, these side effects never required interruption of treatment. Asymptomatic microlithiasis was seen in only one patient after 13 months, which led to treatment being suspended for a period of 3 months after which it was resumed. Fasting serum insulin and insulin area under the curve (AUC) after oral glucose tolerance test (OGTT) fell in all patients. Fasting blood glucose, fructosamine and glucose AUC after OGTT slightly increased during the treatment, but all blood glucose levels (fasting and during OGTT) remained within normal ranges. Lanreotide appears to be a safe and effective treatment in patients with active acromegaly unresolved by surgery. The long-acting formulation avoids the drawbacks associated with either repeated daily injections or continuous infusions of somatostatin analogues. Josef Marek, Third Department of Medicine, Charles University, U nemocnice 1, 128 21 Praha 2, The Czech Republic

scholarly journals Outcomes of Therapy Related Acute Lymphoblastic Leukemia in Adults after Allogeneic Stem Cell Transplantation - Twenty-Year Experience from a Tertiary Care Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5717-5717
Author(s):  
RAM V Nampoothiri ◽  
Arjun Law ◽  
Wilson Lam ◽  
Zeyad Al-Shaibani ◽  
David Loach ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Cox Regression Analysis ◽  
Gvhd Prophylaxis ◽  
One Year ◽  
Prior Malignancy ◽  
Related Mortality

Introduction Therapy related acute leukemias are late complications of treatment with mutagenic agents for both malignant and non-malignant disorders. The prevalence of therapy induced Acute lymphoblastic leukemia(t-ALL) is thought to be much less than that of t-AML/MDS, with our institute reporting a 6.9% prevalence of t-ALL among all patients of adult ALL. There is limited data on role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in t-ALL. Recent reports suggested comparable outcomes with de-novo ALL after allo-HSCT. We aim to report our 20-year experience of allo-HSCT in t-ALL. Patients and Methods We retrospectively reviewed all cases of t-ALL who underwent allo-HSCT at our centre from October 1998 to July 2019. Patients were analysed and compared for demographic features, prior malignancy and its treatment, latent period before ALL, clinical, cytogenetic and molecular characteristics of ALL, induction and consolidation treatment received, transplant details including donor details, conditioning regimens, GVHD prophylaxis as well as post-transplant complications (including transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations), relapse rate, relapse free survival (RFS) and overall survival (OS). Predictors of survival were calculated by Cox-Regression Analysis. Results A total of 18 patients underwent allo-HSCT for t-ALL. M:F ratio was 1:1. Median age at allo-HSCT was 44 years (range 20-70 years). Baseline characteristics, prior malignancy and treatment received are summarized in Table 1. Median latent period from prior malignancy to diagnosis of ALL was 44.8 months (range 6-157 months). Complex cytogenetics was present in 16.7% patients (n=3) while 11q23 rearrangement (KMT2A-MLL) and t(9;22) rearrangement was seen in 33.3% (n=6) and 22.2% (n=4) patients respectively. Median time to allo-HSCT from diagnosis of t-ALL was 5 months. Stem cell donors were matched related, matched unrelated and haplo-identical in 27.8% (n=5), 55.6% (n=10), and 16.7% (n=3) patients, respectively. Conditioning regimen was myeloablative in 44.4% (n=8) patients and reduced intensity in 55.6% (n=10) patients. GVHD Prophylaxis used was ATG-CSA-PTCy in 50% (n=9) patients, CSA/MMF in 22.2% (n=4) patients, and other regimens in 27.8% (n=5) patients. Post HSCT CMV and EBV virus reactivation occurred in- 33.3% (n=6) and 47.1% (n=8) patients, respectively. Acute GVHD (any grade) occurred in 70.6% (n = 12) while chronic GVHD (any grade) occurred in 31.3% (n=5) patients. Transplant related mortality (Death before day 100) occurred in 27.8% (n=5) patients. Four (22.2%) patients relapsed. Median RFS was 4 months (Range 0.5-194 months) while median OS was 5.88 months (Range 0.5-194 months) (Figure 1a&b). One patient (5.5%) had relapse of their primary malignancy (CA Breast) 12 years after allo-HSCT. One year RFS and OS for all patients (excluding patients who have not completed one year of followup after HSCT but have not relapsed or died) was 43.8% and 46.7% respectively. None of the basic disease characteristics, treatment characteristics, or transplant or post-transplant parameters including donor type, conditioning received, GVHD prophylaxis used, occurrence of Acute or chronic GVHD etc. were significantly predictive of OS and RFS on Cox-Regression analysis, though the analysis is limited by the small sample size. Conclusions Therapy related ALL is an uncommon but increasingly recognized disease entity. Our outcomes of Allogeneic HSCT in t-ALL were comparable to that in de novo ALL as per previously reported literature. Multicenter studies on t-ALL with more patients and longer follow up duration may provide us with predictive factors of relapse and survival post allogeneic HSCT. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

scholarly journals The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

2019 ◽  
Vol 3 (4) ◽  
pp. 670-680 ◽  
Author(s):  
Moshe Yeshurun ◽  
Daniel Weisdorf ◽  
Jacob M. Rowe ◽  
Martin S. Tallman ◽  
Mei-Jie Zhang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Low Grade ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Graft Versus Leukemia ◽  
The Impact ◽  
Risk Of Relapse

Abstract Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

scholarly journals Mitochondrial and Oxidative Impacts of Short and Long-term Administration of HAART on HIV Patients

2020 ◽  
Vol 15 (2) ◽  
pp. 110-124
Author(s):  
Joy E. Ikekpeazu ◽  
Oliver C. Orji ◽  
Ikenna K. Uchendu ◽  
Lawrence U.S. Ezeanyika
Keyword(s):  
Treatment Group ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Hiv Patients ◽  
Long Term Treatment ◽  
Term Administration ◽  
Short And Long Term ◽  
One Year

Background and Objective: There may be a possible link between the use of HAART and oxidative stress-related mitochondrial dysfunction in HIV patients. We evaluated the mitochondrial and oxidative impacts of short and long-term administration of HAART on HIV patients attending the Enugu State University Teaching (ESUT) Hospital, Enugu, Nigeria following short and long-term therapy. Methods: 96 patients categorized into four groups of 24 individuals were recruited for the study. Group 1 comprised of age-matched, apparently healthy, sero-negative individuals (the No HIV group); group 2 consisted of HIV sero-positive individuals who had not started any form of treatment (the Treatment naïve group). Individuals in group 3 were known HIV patients on HAART for less than one year (Short-term treatment group), while group 4 comprised of HIV patients on HAART for more than one year (Long-term treatment group). All patients were aged between 18 to 60 years and attended the HIV clinic at the time of the study. Determination of total antioxidant status (TAS in nmol/l), malondialdehyde (MDA in mmol/l), CD4+ count in cells/μl, and genomic studies were all done using standard operative procedures. Results: We found that the long-term treatment group had significantly raised the levels of MDA, as well as significantly diminished TAS compared to the Short-term treatment and No HIV groups (P<0.05). In addition, there was significantly elevated variation in the copy number of mitochondrial genes (mtDNA: D-loop, ATPase 8, TRNALEU uur) in the long-term treatment group. Interpretation and Conclusion: Long-term treatment with HAART increases oxidative stress and causes mitochondrial alterations in HIV patients.

Bone Mineral Density, Fracture Risk and Avascular Bone Necrosis in Childhood Acute Lymphoblastic Leukemia; an Up-Date of the Prospective DUTCH ALL9 Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1962-1962
Author(s):  
Marry M. Van den Heuvel-Eibrink ◽  
Inge M. Van der Sluis ◽  
Bert A. Leeuw ◽  
Gaby Kardos ◽  
Lizet M. te Winkel ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Fracture Risk ◽  
Bone Mineral ◽  
Lymphoblastic Leukemia ◽  
Fracture Incidence ◽  
Rapid Decline ◽  
Mineral Density ◽  
Discontinuation Of Treatment ◽  
One Year

Abstract The high cumulative dose of dexamethasone, applied in the DCOG ALL9 protocol, prompted us to investigate the risk of osteoporosis, fractures and avascular necroses of bone (AVN) in children treated with acute lymphoblastic leukemia (ALL). Fracture risk and incidence of symptomatic AVN was assessed in 778 patients(482 boys, 297 girls), included in the ALL9 protocol since 1997. Total cumulative doses (TCD) of dexamethasone were 1370 mg/m2 and 1244 mg/m2 and of MTX 8.1g/m2 13.6g/m2 for NHR and HR patients respectively. No CNS-irradiation was applied. In children aged >3 years, lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXAscan), at diagnosis(T0), after 32 weeks(T1), at discontinuation of treatment at 109 weeks(T2), and one year after discontinuation of treatment(T3). Results were expressed as standard deviation scores (SDS). Symptomatic AVN was defined as on MRI confirmed AVN lesions in combination with non-vincristine related persistent pain in arms or legs. Fractures were reported in 82/778 (10.5%) patients. Most occurred after mild trauma. No difference was found in fracture incidence between boys and girls. BMD was measured in 387/427 (90.6%) eligible patients. Median BMD-SDS was significantly lower than zero at all times of evaluation, the lowest BMD values were found at T2 (−1.47 SDS). Fracture risk was 3.9 times higher as compared to healthy school children. Fracture incidence was correlated with BMD at T2 and T3(p=0.04 and p=0,04 respectively), but not at T0 and T1. A significant more rapid decline in BMD from T0 to T2 and to T3 was seen in patients with fractures as compared to patients without fractures. After discontinuation of therapy, BMD recovered faster in cases without fractures. Symptomatic AVN occurred in 33/778 (4.2%) of our patients (med age 14, range 6,5–18 years) showing irreversibility in 22 % of the cases. Differences found in the incidence between the centers may suggest underestimation of the risk of fractures and AVN in this prospective study. Children with ALL show a significantly increased fracture risk. Patients with a more severe reduction in BMD during treatment are more susceptible to fractures. The AVN incidence in this protocol did not exceed previous reports of prednisolone-based protocols.

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

Blood ◽  
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.

Long-Term Outcomes after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5534-5534
Author(s):  
Moaath Mustafa Ali ◽  
Donna M Abounader ◽  
Lisa A. Rybicki ◽  
Jamie Starn ◽  
Christina Ferraro ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Long Term Outcomes ◽  
Post Transplant

Abstract Allogeneic hematopoietic cell transplantation (alloHCT) is a curative therapy for high-risk acute lymphoblastic leukemia (ALL). However, long-term outcomes after alloHCT for adult ALL have not been well described. We conducted a retrospective cohort study of 72 consecutive adult ALL patients who underwent a first myeloablative alloHCT at our institution from January 2000-December 2013. Median age at HCT was 38 yrs (range, 18-62), 40 (56%) were male, 18 (38%) had high HCT CI score, 14 (19%) had prior CNS leukemia and 35 (49%) had BCR-ABL+ disease. Donor source was HLA-matched related donor for 50% patients and 90% received PBSC as graft source. All patients were transplanted in CR (72% were in 1st or 2nd CR) and 92% received T-cell replete grafts. Median time from diagnosis to alloHCT was 5 months (range, 2-90). The incidences of grade II-IV and III-IV acute GvHD, chronic GvHD and extensive chronic GvHD were 43%, 13%, 51% and 36%, respectively. The median follow-up for our cohort is 76 months. At 6 years after HCT, probability of overall survival (OS) was 33% (95% CI, 21-44%) and relapse-free survival (RFS) was 30% (95% CI, 19-42%), and the cumulative incidence of relapse was 36% (95% CI, 25-48%) and non-relapse mortality (NRM) was 37% (95% CI, 26-49%). The most common causes of death were relapse (43%) and infection (21%); majority of relapses occurred within the first 2-years post-transplantation. There were no second cancer related deaths. In multivariable analyses, factors significantly associated with OS were HCT CI score (HR 2.69 for high vs. low/int., P=0.002) and CMV status (HR 2.62 for donor+ vs. others, P=0.05). HCT CI score was the only predictive factor for RFS (HR 2.26 for high, P=0.007). We also compared outcomes by BCR-ABL status. BCR-ABL+ patients were older (median age 42 vs. 36 yrs, p=0.02), had low HCT CI score (34% vs 22%, p=0.01), were more likely to be in CR1 (74% vs. 32%, p=0.002), and as a result, proceeded to HCT sooner after diagnosis (median 4 vs 7 months, p=<0.001). For BCR-ABL+ and BCR-ABL- patients, 6 year OS was 41% and 25%, RFS was 40% and 21%, relapse was 27% and 45% and NRM was 38% and 36% (P=NS for all comparisons). Myeloablative alloHCT can provide long-term survival for selected high-risk adult ALL patients. Relapses are relatively uncommon after 2 years post-transplant. Long-term NRM is high in this population and we did not observe a plateau in its incidence until 7.5 years post-transplant, suggesting the need for long-term follow up to prevent and manage late complications of alloHCT. Figure 1. Figure 1. Disclosures Majhail: Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

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