Early-onset Cardiotoxicity assessment related to anthracycline in children with leukemia. A Prospective Study

Background: Acute leukemias are the most frequent malignancies in children. Advances in treatment have improved the overall survival to 80%. Almost 10% of children with cancer develop clinical cardiac toxicity. Total anthracycline cumulative dose is a risk factor for early-onset cardiotoxicity. Objective: To describe the incidence of early-onset cardiotoxicity in children with acute leukemia treated with chemotherapy. Methods: A prospective descriptive study of patients >1 y and <18 years diagnosed with acute leukemia. Assessed with electrocardiogram, echocardiography, and blood biomarkers at diagnosis and during the follow-up. Results: 94 patients with acute lymphoblastic leukemia and 18 with acute myeloid leukemia were included. 20 patients (17.9%) developed early-onset cardiotoxicity. Statistically significant data was seen after anthracycline dose >150 mg/m2, between the first echocardiographic evaluation and posterior analyses in the left ventricular fraction ejection with Teicholz p 0.05, Simpson p 0.018 and GLS p 0.004. In this study, there was no relation between blood biomarkers and cardiotoxicity. Conclusions: Cancer therapeutic-related cardiac dysfunction is related to anthracycline cumulative dose. In this study, echocardiographic follow-up was useful to predict risk factors for early cardiac dysfunction.

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Pattern of childhood acute leukemia presentation at a tertiary hospital in Nigeria: a five-year review

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20184202 ◽

2018 ◽

Vol 5 (6) ◽

pp. 2123

Author(s):

Adewumi B. Oyesakin ◽

Vincent E. Nwatah ◽

Nwankwo U. Ukpai ◽

Ekaette I. David ◽

Tamunomieibi T. Wakama ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Clinical Features ◽

Childhood Leukemia ◽

Lymphoblastic Leukemia ◽

Tertiary Hospital ◽

Cross Sectional ◽

Acute Leukemias ◽

Lost To Follow Up

Background: Acute leukemia is the most common childhood malignancy but its occurrence in low- and middle-income countries are under-reported. Its pattern of presentation varies depending on several factors. The objective of this report is to determine the pattern of presentation of acute leukemias in children at a tertiary hospital in Nigeria.Methods: A retrospective cross-sectional study of children managed for acute leukemia at the Paediatric Department in a 5-year period. Of 31 patients, 27 had adequate records, which were reviewed. Data collected include patient’s demographics, clinical features and treatment outcome.Results: There were 16 males and 11 females, aged 8 months to 16 years (mean 7.45 years ±4.75 SD). The pattern of clinical features were fever (85.2%), pallor (92.6%) and splenomegaly (51.9%). The specific leukemia type ratio for Acute Myeloid leukemia (AML) and Acute lymphoblastic leukemia (ALL) was 1: 2.9. The parents of three patients took their children away before commencement of treatment, one patient completed treatment and 6 (22.2%) died before completing treatment. Nearly half of the patients were lost to follow up to seek alternative care while 9 (33.3%) of the patients were in remission at last follow up. Lost to follow-up was found not to be significantly associated with socioeconomic status, age and sex respectively.Conclusions: Acute lymphoblastic leukemia remains the predominant type of childhood leukemia in our setting. Majority of the patients presented with fever and pallor moreover the default to follow-up plagues treatment completion.

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Wilms tumor (WT)1 gene expression in children with acute leukemia in Serbia

Genetika ◽

10.2298/gensr1601409j ◽

2016 ◽

Vol 48 (1) ◽

pp. 409-421

Author(s):

Srdja Jankovic ◽

Irena Marjanovic ◽

Natasa Tosic ◽

Nikola Kotur ◽

Lidija Dokmanovic ◽

...

Keyword(s):

Bone Marrow ◽

Acute Leukemia ◽

Wilms Tumor ◽

Lymphoblastic Leukemia ◽

Acute Leukemias ◽

Exact Test ◽

Wide Range ◽

Level Of Significance ◽

Fourth Quartile

Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse-transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median ? SD: 139.42 ? 244.03) than those with ALL (1.18 ? 54.37; Mann-Whitney U=82; p<0.01) and ITP (0.76 ? 1.01; U=32; p<0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 ? 192.52) than in 6 who succumbed to the disease (104.29 ? 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1-month WT1 expression in the fourth quartile survived (Fisher?s exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context. [Projekat Ministarstva nauke Republike Srbije, br. 41004] This article has been corrected. Link to the correction <a href="http://dx.doi.org/10.2298/GENRSR1602799E">10.2298/GENRSR1602799E</a>

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Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0504-cp ◽

2017 ◽

Vol 141 (10) ◽

pp. 1342-1393 ◽

Cited By ~ 50

Author(s):

Daniel A. Arber ◽

Michael J. Borowitz ◽

Melissa Cessna ◽

Joan Etzell ◽

Kathryn Foucar ◽

...

Keyword(s):

Genetic Testing ◽

Acute Leukemia ◽

Lymphoblastic Leukemia ◽

Molecular Genetic ◽

Clinical Information ◽

Molecular Genetic Testing ◽

Acute Leukemias ◽

Prognostic Evaluation ◽

The Public ◽

American Society

Context.— A complete diagnosis of acute leukemia requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping and karyotype analysis, and often, molecular genetic testing. Although many aspects of the workup for acute leukemia are well accepted, few guidelines have addressed the different aspects of the diagnostic evaluation of samples from patients suspected to have acute leukemia. Objective.— To develop a guideline for treating physicians and pathologists involved in the diagnostic and prognostic evaluation of new acute leukemia samples, including acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage. Design.— The College of American Pathologists and the American Society of Hematology convened a panel of experts in hematology and hematopathology to develop recommendations. A systematic evidence review was conducted to address 6 key questions. Recommendations were derived from strength of evidence, feedback received during the public comment period, and expert panel consensus. Results.— Twenty-seven guideline statements were established, which ranged from recommendations on what clinical and laboratory information should be available as part of the diagnostic and prognostic evaluation of acute leukemia samples to what types of testing should be performed routinely, with recommendations on where such testing should be performed and how the results should be reported. Conclusions.— The guideline provides a framework for the multiple steps, including laboratory testing, in the evaluation of acute leukemia samples. Some aspects of the guideline, especially molecular genetic testing in acute leukemia, are rapidly changing with new supportive literature, which will require on-going updates for the guideline to remain relevant.

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Second Allogeneic Hematopoietic Stem Cell Transplantation for Post-Transplant Relapsed Acute Leukemia in Children - an EBMT PDWP Retrospective Study

Blood ◽

10.1182/blood.v130.suppl_1.912.912 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 912-912

Author(s):

Isaac Yaniv ◽

Aviva C. Krauss ◽

Eric Beohou ◽

Arnaud Dalissier ◽

Selim Corbacioglu ◽

...

Keyword(s):

Prognostic Factors ◽

Prognostic Factor ◽

Acute Leukemia ◽

Pediatric Patients ◽

Multivariate Analyses ◽

Acute Leukemias ◽

Hematopoietic Stem ◽

Entire Cohort

Abstract Introduction Using the EBMT registry, we retrospectively analyzed outcomes for 373 pediatric patients who underwent second allogeneic transplant for relapsed acute leukemia at 120 centers in 32 countries, between the years 2004 and 2013, in an attempt to assess relapse, survival, GVHD and other outcomes, as well as identify factors correlating with prognosis in this cohort of patients. To our knowledge, this is the largest analysis of pediatric patients undergoing second allogeneic HSCT for relapsed acute leukemia to date. This allowed for an independent analysis of each disease, including 214 patients with ALL and 159 with AML. Patients and Methods Centers received a questionnaire completing data already available in the ProMISe database on patients between 0-18 years of age treated between 2004 and 2013. Results A total of 387 patients received a second SCT after relapse. 373 have been included in the analysis, 214 for ALL and 159 for AML. Detailed data were available for 201 patients from 48 centers; for the remainder, analysis was based on the registry. For the entire cohort overall survival (OS) at 2 and 5 years were 38% and 29%, and leukemia free survival (LFS) 30% and 25% respectively. ALL: With a median follow up from 2nd SCT of 36.4 months, OS at 1 and 5 years were 47% and 28% respectively. LFS was 39% and 28% respectively. NRM at 2 years was 22%. In multivariate analyses favorable prognostic factors for both OS and LFS were: CR prior to 2nd SCT (p=0.0001), interval > 12 months between transplants (p=0.0007), use of myeloablative conditioning (p=0.039) and the presence of cGvHD after the first SCT (p=0.0001). Good prognostic factor for low NRM was interval of more than 12 months between transplants (p=0.0002). AML: With a median follow up from 2nd SCT of 50 months, OS at 1 and 5 years were 44% and 15% respectively. LFS was 28% and 15% respectively. NRM at 2 years was 18%. In multivariate analyses, favorable prognostic factors for OS as well as LFS were: CR prior to 2nd SCT (p=0.031;0.044 respectively), interval > 6 months between transplants (p=0.0003;0.0001 respectively), and having cGvHD after the first SCT (p=0.0001). Most patients experience disease relapse or NRM within the first year after their second transplant. This observation seems to be more consistent in patients transplanted for ALL, with more changes over time in patients with AML. For ALL in particular, the 2-year incidences of relapse, NRM and LFS were not different from those at 5-years. Even in the relapse setting, survival rates for patients with ALL remain superior to patients with AML, consistent with the prognostic differences at diagnosis. Our findings, consistent for the AML and ALL subgroups, suggest that cGHVD prior to second HSCT is associated with better outcome. The identification of cGHVD prior to second transplant has not been heretofore described as a favorable prognostic factor. This strong correlation merits further study, specifically as to the underlying biology for this association. Conclusion Children with relapsed acute leukemias have a substantial chance to become long term survivors following a second SCT. CR prior to second SCT, longer interval between transplants and the presence of cGvHD after the first transplant, are favorable prognostic factors for ALL and AML. Our findings may help physicians in discussing the risk-benefit of a second transplant. These results are particularly relevant in an era where an explosion of new therapies, specifically targeted therapies and those that modulate the immune response, behoove us to carefully identify subpopulations of patients for whom specific therapies are appropriate. Novel approaches are needed to minimize relapse risk as well as short and long term morbidity in these pediatric patients while considering a second SCT for relapsed acute leukemia. Disclosures Corbacioglu: Jazz Pharmaceuticals: Consultancy, Honoraria. Bader: Novartis, Medac, Amgen, Riemser, Neovii: Consultancy, Honoraria, Research Funding.

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Acute Leukemia

10.2310/im.1247 ◽

2016 ◽

Author(s):

Richard A. Larson ◽

Roland B Walter

Keyword(s):

Acute Myeloid Leukemia ◽

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

Myeloid Leukemia ◽

Who Classification ◽

Lymphoblastic Leukemia ◽

World Health ◽

Acute Leukemias ◽

Acute Myeloid

The acute leukemias are malignant clonal disorders characterized by aberrant differentiation and proliferation of transformed hematopoietic progenitor cells. These cells accumulate within the bone marrow and lead to suppression of the production of normal blood cells, with resulting symptoms from varying degrees of anemia, neutropenia, and thrombocytopenia or from infiltration into tissues. They are currently classified by their presumed cell of origin, although the field is moving rapidly to genetic subclassification. This review covers epidemiology; etiology; classiﬁcation of leukemia by morphology, immunophenotyping, and cytogenetic/molecular abnormalities; cytogenetics of acute leukemia; general principles of therapy; acute myeloid leukemia; acute lymphoblastic leukemia; and future possibilities. The figure shows the incidence of acute leukemias in the United States. Tables list World Health Organization (WHO) classification of acute myeloid leukemia and related neoplasms, expression of cell surface and cytoplasmic markers for the diagnosis of acute myeloid leukemia and mixed-phenotype acute leukemia, WHO classification of acute lymphoblastic leukemia, WHO classification of acute leukemias of ambiguous lineage, WHO classification of myelodysplastic syndromes, European LeukemiaNet cytogenetic and molecular genetic subsets in acute myeloid leukemia with prognostic importance, cytogenetic and molecular subtypes of acute lymphoblastic leukemia, terminology used in leukemia treatment, and treatment outcome for adults with acute leukemia. This review contains 1 highly rendered figure, 9 tables, and 117 references.

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Bone Marrow Transplantation in Patients With Acute Leukemia In Cuba: Results From the Last 30 Years and New Opportunities Through International Collaboration

Journal of Global Oncology ◽

10.1200/jgo.18.00109 ◽

2018 ◽

pp. 1-7

Author(s):

José Carnot Uria ◽

Calixto Hernández Cruz ◽

Jorge Muñío Perurena ◽

Wilfredo Torres Yribar ◽

Jesús Diego de la Campa ◽

...

Keyword(s):

Acute Leukemia ◽

Marrow Transplantation ◽

Lymphoblastic Leukemia ◽

Disease Relapse ◽

Eligibility Criteria ◽

University Of Illinois ◽

Blood And Marrow Transplantation ◽

Scientific Report ◽

Related Mortality

Blood and marrow transplantation (BMT) has been performed in Cuba for over 30 years with limited resources and without international relationships. Researchers from University of Illinois at Chicago and Hermanos Ameijeiras Hospital (HAH) in Havana collaborated on retrospectively analyzing 101 consecutive patients with adult acute leukemia who received BMT at HAH from June 1986 to January 2016. Of these, 82 had acute myeloid leukemia (AML) and 19 had acute lymphoblastic leukemia (ALL). BMT eligibility criteria included prior morphologic complete remission, no severe comorbidities, and age between 16 and 60 years. Patients with an HLA-matched donor received an allogeneic BMT, whereas the others received an autologous BMT. All patients received fresh stem cells from marrow (80%) or mobilized peripheral blood (19%). Of 82 patients with AML, 35 received an allogeneic (AML-allo) and 47 an autologous (AML-auto) BMT. Both groups had comparable median age (37 years) and follow-up of survivors. Overall survival (OS) was 34% in AML-allo and 38% in AML-auto. The transplant-related mortality rate was 40% in AML-allo and 17% in AML-auto, whereas the relapse-related mortality rates were 25% and 40%, respectively. Of the 19 patients with ALL, six received an allogeneic transplant. Of these, transplant-related mortality occurred in one patient and three died after disease relapse (OS, 33%). Of 13 patients who received autologous transplants, transplant-related mortality occurred in three and six died after disease relapse (OS, 31%). To our knowledge, this is the first scientific report on BMT performed in patients with acute leukemia in Cuba. The collaboration between University of Illinois at Chicago and HAH will further develop capacity building in research and implementation of new diagnostic and therapeutic strategies in Cuba.

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Clonal Evolution of B-Cell Acute Lymphoblastic Leukemia with del(9)(p13p21) into Mixed Phenotype Acute Leukemia Presenting as an Isolated Testicular Relapse

Reports ◽

10.3390/reports2030018 ◽

2019 ◽

Vol 2 (3) ◽

pp. 18 ◽

Cited By ~ 1

Author(s):

Miller ◽

Park ◽

Saxe ◽

Lew ◽

Raikar

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Acute Leukemia ◽

B Cell ◽

Lymphoblastic Leukemia ◽

Clonal Evolution ◽

Acute Leukemias ◽

Cytogenetic Aberrations ◽

Mixed Phenotype Acute Leukemia ◽

Cell Acute Lymphoblastic Leukemia ◽

Mixed Phenotype

Lineage switch in acute leukemias is a well-reported occurrence; however, most of these cases involve a switch from either lymphoid to myeloid or myeloid to lymphoid lineage. Here, we report a case of a 14-year-old male with B-cell acute lymphoblastic leukemia (B-ALL) who initially responded well to standard chemotherapy but then later developed mixed phenotype acute leukemia (MPAL) at relapse, likely reflecting a clonal evolution of the original leukemia with a partial phenotypic shift. The patient had a del(9)(p13p21) in his leukemia blasts at diagnosis, and the deletion persisted at relapse along with multiple additional cytogenetic aberrations. Interestingly, the patient presented with an isolated testicular lesion at relapse, which on further analysis revealed both a lymphoid and myeloid component. Unfortunately, the patient did not respond well to treatment at relapse and eventually succumbed to his disease. To our knowledge, an isolated extramedullary MPAL at relapse in a patient with previously diagnosed B-ALL has not been reported in the literature before.

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Characterization of Thy-1 (CDw90) expression in CD34+ acute leukemia

Blood ◽

10.1182/blood.v86.1.60.bloodjournal86160 ◽

1995 ◽

Vol 86 (1) ◽

pp. 60-65 ◽

Cited By ~ 14

Author(s):

JT Holden ◽

RB Geller ◽

DC Farhi ◽

HK Holland ◽

LL Stempora ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Acute Leukemia ◽

Lymphoblastic Leukemia ◽

Blast Crisis ◽

Myelogenous Leukemia ◽

Acute Leukemias ◽

Hematopoietic Stem

Thy-1 (CDw90) is a phosphatidylinositol-anchored cell surface molecule which, when coexpressed with CD34 in normal human bone marrow, identifies a population of immature cells that includes putative hematopoietic stem cells. To date, the characterization of Thy-1 expression has been confined largely to normal tissues and cell lines. In this study, we evaluated the frequency and intensity of Thy-1 expression as defined by reactivity with the anti-Thy-1 antibody 5E10 in 38 cases of CD34+ acute leukemia (21 acute myelogenous leukemia [AML], 8 chronic myelogenous leukemia [CML] in blast crisis, and 9 acute lymphoblastic leukemia [ALL]). In 34 of 38 cases (89%) the CD34+ cells lacked expression of the Thy-1 antigen. High-density Thy-1 expression was found in 1 case of CML in lymphoid blast crisis, and low- density Thy-1 expression was identified on a portion of the leukemic cells in 2 cases of AML with myelodysplastic features, and 1 case of CML in myeloid blast crisis, suggesting a possible correlation between Thy-1 expression and certain instances of stem cell disorders such as CML and AML with dysplastic features. In contrast, the dissociation of Thy-1 and CD34 expression in the majority of acute leukemias studied suggests that the development of these leukemias occurs at a later stage than the hematopoietic stem cell. Characterization of Thy-1 expression in acute leukemia may eventually provide insights into the origin of the disease. In addition, separation of leukemic blasts from normal stem cells based on Thy-1 expression may prove useful in assessing residual disease, as well as in excluding leukemic blasts from stem cell preparations destined for autologous bone marrow or peripheral stem cell transplantation.

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The Reliability and Specificity of c-kit for the Diagnosis of Acute Myeloid Leukemias and Undifferentiated Leukemias

Blood ◽

10.1182/blood.v92.2.596 ◽

1998 ◽

Vol 92 (2) ◽

pp. 596-599 ◽

Cited By ~ 134

Author(s):

M.C. Bene ◽

M. Bernier ◽

R.O. Casasnovas ◽

G. Castoldi ◽

W. Knapp ◽

...

Keyword(s):

Acute Leukemia ◽

De Novo ◽

Lymphoblastic Leukemia ◽

Cell Lineage ◽

Specific Marker ◽

Acute Leukemias ◽

Routine Basis ◽

Immunological Classification ◽

B Lineage ◽

Acute Myeloid

Abstract We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819 acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4 undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of the French-American-British (FAB) subtype, one third of BAL, all four AUL, but only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified as: T-cell lineage (two thirds), mainly pro-T–ALL or T-I, and B lineage (one third); cells from 62% of these ALL cases coexpressed other myeloid markers (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML or ALL cases according to age being similar in the adult and pediatric groups. Our findings demonstrate that c-kit is a reliable and specific marker to detect leukemia cells committed to the myeloid lineage, and therefore should be included in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid commitment of the blasts. c-kit expression should score higher, at least one point, in the system currently applied to the diagnosis of BAL, as its myeloid specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c-kit identifies a subgroup of cases, which may correspond to leukemias either arising from early prothymocytes and/or early hematopoietic cells, both able to differentiate to the lymphoid and myeloid pathways.

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Chronic Progressive Cardiac Dysfunction Years After Doxorubicin Therapy for Childhood Acute Lymphoblastic Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2005.12.121 ◽

2005 ◽

Vol 23 (12) ◽

pp. 2629-2636 ◽

Cited By ~ 440

Author(s):

Steven E. Lipshultz ◽

Stuart R. Lipsitz ◽

Stephen E. Sallan ◽

Virginia M. Dalton ◽

Suzanne M. Mone ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Left Ventricular ◽

Childhood Acute Lymphoblastic Leukemia ◽

Cardiac Abnormalities ◽

Z Scores ◽

Long Term Survivors ◽

Fractional Shortening

Purpose Cross-sectional studies show that cardiac abnormalities are common in long-term survivors of doxorubicin-treated childhood malignancies. Longitudinal data, however, are rare. Methods Serial echocardiograms (N = 499) were obtained from 115 doxorubicin-treated long-term survivors of childhood acute lymphoblastic leukemia (median age at diagnosis, 4.8 years; median follow-up after completion of doxorubicin, 11.8 years). Results were expressed as z scores to indicate the number of standard deviations (SDs) above (+) or below (−) the normal predicted value. Median individual and cumulative doxorubicin doses were 30 mg/m2 per dose and 352 mg/m2, respectively. Results Left ventricular fractional shortening was significantly reduced after doxorubicin therapy, and the reduction was related to cumulative dose. z scores for fractional shortening transiently improved before falling to −2.76 more than 12 years after diagnosis. Reduced fractional shortening was related to impaired contractility and increasing afterload, consequences of a progressive reduction of ventricular mass, and wall thickness relative to body-surface area. Left ventricular contractility fell significantly over time and was depressed at last follow-up in patients receiving more than 300 mg/m2 of doxorubicin. Systolic and diastolic blood pressures were below normal more than 9 years after diagnosis. Even patients receiving lower cumulative doxorubicin doses experienced reduced mass and dimension. Fractional shortening and dimension at the end of therapy predicted these parameters 11.8 years later. Conclusion Cardiac abnormalities were persistent and progressive after doxorubicin therapy. Inadequate ventricular mass with chronic afterload excess was associated with progressive contractile deficit and possibly reduced cardiac output and restrictive cardiomyopathy. The deficits were worst after highest cumulative doses of doxorubicin, but appeared even after low doses.

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