Blackfan-Diamond disease and malignancy: cause effect relationships?]

The authors report on a 24-year old patient with Blackfan-Diamond syndrome who developed a Hodgkin's disease. This patient became transfusion-dependent at the age of 10, after an initial period of corticosensitivity, and after failure of androgens. He developed hemochromatosis despite from parenteral chelation therapy. He died of infectious complications 4 months after the diagnosis of Hodgkin's lymphoma. A review of the literature shows an increased incidence of malignancies in Blackfan-Diamond syndrome (three cases of leukemia), and in similar disease (thalassemia and sickle cell disease), but not in other patients with hemosiderosis (primitive hemochromatosis, end-stage renal failure under dialysis). Etiopathogenic hypotheses are discussed.     

Hodgkin's disease in a child with sickle cell disease treated with hydroxyurea

Hydroxyurea (HU) is an oral drug that ameliorates the clinical course of sickle cell anemia by □increasing the levels of fetal hemoglobin and decreasing the adhesion of red cells to endothelium. Although HU has minimal short-term toxicity, few data are available about the long-term safety and the potential risk for carcinogenesis or leukemogenesis. An 8-year-old child with sickle cell / β0- thalassemia who received HU treatment for painful crises is described. Six months after the initiation of the HU treatment he developed Hodgkin's disease, lymphocyte predominance subtype. Chemotherapy induced a complete remission. After discontinuation of chemotherapy the painful crises recurred and bone marrow transplantation was decided at the age of 12 years. Two years after the bone marrow transplantation, the child is in complete remission without painful crises. Although the authors suggest that the development of Hodgkin's disease is a coexisting event, questions arise about the safety of HU treatment in childhood.     

Impact of environmental tobacco smoke on children with sickle cell disease

BACKGROUND: Parallels between the biological effects of exposure to environmental tobacco smoke (ETS) on nonsmokers and the pathophysiology of sickle cell disease (SCD) suggest that complications of SCD could be exacerbated by ETS exposure. OBJECTIVE: To determine whether children with SCD who are exposed to ETS at home have more sickle cell crises than do those who live in nonsmoking households. DESIGN: A retrospective cohort study in which ETS exposure was measured by using a survey of caretakers and patients. SETTING: A university-based pediatric sickle cell center. PARTICIPANTS: Fifty-two of 66 eligible children aged 2 to 18 years with SCD. OUTCOME MEASURES: The number of sickle cell vaso-occlusive crises requiring hospitalization per patient during the 2-year study (inpatient sickle cell crises). Total hospital days and hospital costs were secondary outcome measures. RESULTS: Patients exposed to ETS had more inpatient sickle cell crises than did unexposed patients (mean +/- SD, 3.7 +/- 5.7 vs 1.7 +/- 3.5; P =.02), and this association retained significance after adjustment for important covariates (risk ratio, 1.9; 95% confidence interval, 1.3-2.7). Hospital costs were greater in the exposed group than in the unexposed group (mean +/- SD, 21,671 US dollars +/- 41,809 US dollars vs 9705 US dollars +/- 19 146 US dollars; effect estimate, 11.4; 95% confidence interval, 1.0-129.5). CONCLUSIONS: Children with SCD who are exposed to ETS have a higher risk of sickle cell crises requiring hospitalization than do those not exposed, independent of other factors known to increase the frequency of sickle cell crises. Decreasing the exposure of these children to ETS could reduce morbidity and may provide cost savings.     

Life threatening parvovirus B19 and herpes simplex virus associated acute myocardial dysfunction in a child with homozygous sickle cell disease

Human parvovirus (HPV) B19, a common infection, frequently causes transient red cell aplasia in children with hemolytic anemia, such as sickle cell disease (SCD). It was considered to be a self-limited condition, easily treated with blood transfusion. However, acute splenic sequestration, acute chest syndrome, nephrotic syndrome, and stroke have been reported in SCD patients following HPV B19 infection. We report a 3-year-old child with SCD who developed fulminant myocarditis following HPV B19-related aplastic crisis. The diagnosis of myocarditis should be considered in a patient with hemolytic anemia with an infection with HPV B19 who develops signs of cardiopulmonary failure despite correction of anemia.     

Acute liver failure due to T cell lymphoma without hepatic infiltration

Hepatomegaly and alterations in hepatic function are common to all patients with sickle-cell disease. In these patients, hepatic sickling is a manifestation of severe intrahepatic vaso-oclusive crises, even at levels of 25 % HbS and hematocrits of more than 45-50 %, which in 10 % of cases can lead to acute hepatic failure (AHF). AHF can be due to a variety of causes, including hematologic malignancies, but T cell lymphoma, which is usually secondary to diffuse hepatic infiltration and ischemia, is an exceptional cause, although other mechanisms can be involved. Cytokines released by lymphomas have recently been implicated as a cause of AHF.We describe a black girl with sickle cell disease, who developed AHF due to T cell lymphoma without lymphomatous infiltration of the liver. The only mechanism found to explain the clinical findings was release of cytokines by lymphoma. In patients with AHF of unknown etiology we propose early liver biopsy, because prognosis depends on the presence or absence of hepatic tumour infiltration. If AHF develops in a patient with diagnosed malignant disease, cytokine release may be the cause of AHF. Consequently, early diagnosis of the underlying disease and provision of liver support, as well as direct removal of inflammatory mediators from the circulation by exchange transfusion or other methods, should be the main priorities.     

Simultaneous presentation of relapsing Hodgkin's disease and treatment-related non-Hodgkin's lymphoma

A 55-year-old white man was diagnosed in 1975 with Hodgkin's disease stage IIA, mixed cellularity. He was treated with 4,500 rads to an inverted-Y field followed by six cycles of MOPP and remained in complete remission. In 1983 a right axillary lymph node biopsy showed recurrent Hodgkin's disease, mixed cellularity. While receiving his initial chemotherapy he developed persistent epigastric distress. Endoscopic gastric biopsy demonstrated a diffuse large-cell non-Hodgkin's lymphoma. Surface marker studies confirmed the separate identity of these two malignant lymphoproliferative processes. This represents the first reported simultaneous occurrence of relapsing Hodgkin's disease with treatment-related non-Hodgkin's lymphoma.     

The spleen in the sickling disorders: an update

In early life, patients with sickle cell disease (SCD) can have acute, life-threatening emergencies related to splenic hypofunction (overwhelming bacterial sepsis), as well as anemic crises from acute splenic sequestration because of sudden pooling of blood in the spleen. The landmark penicillin prophylaxis study in 1985 showed a remarkable decrease in mortality from sepsis in young children with SCD who were treated with oral penicillin prophylaxis compared to placebo. Since that study, newborns are screened for SCD and placed on oral penicillin prophylaxis in nearly all of the United States, as well as in other countries where the disease is highly prevalent. The previously described permanent, complete and nearly universal “autosplenectomy” emerging by late childhood or early adulthood is now challenged by recent findings of reversibility of splenic dysfunction by the antisickling drug hydroxyurea or by successful allogeneic stem cell transplantation, even in older patients. Imaging techniques for hypofunction of the spleen are the most commonly used modalities to guide the clinician in decisions regarding medical or surgical management.     

Splenectomy and acute splenic sequestration crises in sickle cell disease

Acute splenic sequestration crises (ASSC) is one of the complications of sickle cell disease (SCD) that can be life-threatening due to loss of blood volume. Over a 5-year period, we have treated 19 patients ranging in age from 4 to 32 years with ASSC. There were 14 males and 5 females; 17 had homozygous SCD and the other 2 had sickle thalassemia. Two patients presented with severe anemia and acute circulatory collapse; 1 of them developed residual weakness of his limbs and decreased visual acuity. Nine patients underwent splenectomy after major episodes of sequestration while the remaining 10 had recurrent minor episodes of sequestration. The clinical features and the role of splenectomy are discussed.     

Assessing barriers and facilitators to transition in sickle cell disease care prior to implementation of a formalized program

Over 95% of children with sickle cell disease (SCD) survive into adulthood in the United States. However, early mortality remains a problem, especially in persons between the ages of 18 and 35. One possible explanation for the increased mortality rate in young adults is difficulties in engaging in care during the transition from a heavily contiguous pediatric healthcare model to a more self-reliant adult healthcare model. The goal of this study was to identify potential facilitators and barriers to a successful transfer in care from the pediatric to adult SCD program before the formation of a formal transition program. This is a retrospective cohort study of transition outcomes for 472 individuals with SCD (all genotypes) treated at the University of Alabama at Birmingham (UAB) sickle cell clinic (aged 18–24). The primary outcome was whether the patient continued care in (any) adult SCD program (defined as being seen at least once in an adult hematology/SCD clinic). One hundred eighty-eight (45%) transition age patients successfully transferred to adult care. Facilitators to successful transfer in care included being treated at the same hospital for both pediatric and adult programs, having the genotype HbSS, and/or receiving an SCD-modifying therapy at the time of transition (hydroxyurea and/or red cell transfusion therapy). Of primary interest, many of the patients who failed to transition to an adult clinic were lost to follow-up prior to 15 years of age. Importantly, these patients who had previously been labeled as “transition failures,” were lost to follow-up long before the transition age. Early engagement is needed for this population.     

Minor elective surgical procedures using general anesthesia in children with sickle cell anemia without pre-operative blood transfusion

BACKGROUND: Pre-operative red blood cell (RBC) transfusions are often recommended for patients with sickle cell disease (SCD) who require elective surgery under general anesthesia. However, definitive randomized studies demonstrating the benefit of transfusions in this setting have not been conducted. In particular, the merits of transfusion prior to minor or low-risk surgical procedures in children with SCD have not been demonstrated. PROCEDURE: We hypothesized that children with sickle cell anemia (Hb SS) who have minor elective surgical procedures develop few complications even without pre-operative transfusion. We accessed our Comprehensive Sickle Cell Program's Database to identify all such procedures performed during a 13-year period. Medical records were reviewed to characterize the surgical procedure, the use of transfusions, and perioperative complications. RESULTS: Twenty-eight children with Hb SS had a total of 38 minor surgical procedures. No perioperative transfusions were given in 34 of the cases (85%). Five of these 34 surgeries (15%) were associated with minor post-operative complications (fever or transient pain). No post-operative acute chest syndrome was encountered. CONCLUSIONS: Minor or low-risk elective surgical procedures in children with Hb SS may not routinely require pre-operative transfusion. A randomized clinical trial to compare transfusion with no transfusion for minor surgical procedures is needed.     

Long-term follow-up of pediatric sickle cell disease patients with abnormal high velocities on transcranial Doppler

Cerebral arteriopathy can be detected in children with sickle cell disease (SCD) by transcranial Doppler (TCD). Abnormally high velocities are predictive of high stroke risk, which can be reduced by transfusion therapy. We report the results of the screening of 291 SCD children followed in our center, including the clinical and imaging follow-up of 35 children with abnormal TCDs who were placed on transfusion therapy. We postulated that patients with normal MRA findings and abnormal TCD velocities that normalized on a transfusion program could be safely treated with hydroxyurea (HU). We report their outcome (median follow-up of 4.4 years). Of 13 patients with normalized velocities on transfusion, 10 had normal MRAs, and transfusion therapy was stopped and HU begun. Four of these ten patients redeveloped high velocities off transfusion, so currently only six remain transfusion-free. Six other transplanted patients remain transfusion-free. Abnormal TCD velocities detect a high-risk group, justifying the research for suitable transplant donors. Multicenter studies comparing HU therapy to long-term transfusion might help identify which patients can avoid transfusion and its complications while avoiding vasculopathy.     

Outcomes of a preoperative risk-based transfusion assignment protocol in sickle cell disease patients: a single-center retrospective study from Saudi Arabia

Abstract

Many patients with sickle cell disease (SCD) need surgical management during their lifetime. The best approach for preoperative transfusion in SCD is still to be determined. In this single-center retrospective study, we included HBSS/HBS-Beta⁰-thalassemia patients younger than 16?years of age who underwent surgery between January 2008 and July 2019. Preoperative transfusion assignment (PTA) was based on SCD severity and surgical risk. Patients were assigned to no transfusion, simple transfusion, or exchange transfusion. A total of 284 patients were identified and 66 (23%) underwent 78 procedures. Mean age at the time of procedure was 8 (5–11) years, mean baseline hemoglobin was 8.5 (7.8–9.3) g/dl, and mean hemoglobin F was 18.4?±?8.2%. SCD severity was low-risk in 57 (73%) and high-risk in 21 (27%) patients. Surgical risk was low-risk in 20 (25.6%) and medium-risk in 58 (74.4%) procedures. PTA was no transfusion in 17 (22%), simple transfusion in 40 (51%), and exchange transfusion in 21 (27%) procedures. Postoperative complications occurred in five (6.4%) of procedures only in the simple transfusion group (three acute chest syndrome, one hemolytic anemia, one pain crisis) undergoing medium-risk surgery. Preoperative risk-based transfusion assignment is feasible. Despite a high baseline hemoglobin level in the no transfusion group, none of the patients developed postoperative complications. It is possible that the high baseline hemoglobin F phenotype was protective and indicates the need to study the risk/benefit of interventions used in this phenotype.     

Management of severe chronic pain with methadone in pediatric patients with sickle cell disease

Vasocclusive pain crises are common among pediatric patients with sickle cell disease (SCD). Some patients with repeated pain crises develop chronic pain. We performed a retrospective cohort study of pediatric patients with SCD with chronic pain treated with methadone. We identified a significant reduction in pain hospitalizations following methadone treatment (0.35 ± 0.19 vs. 0.19 ± 0.17 hospitalizations/month, P = 0.016). In addition, we did not observe overt organ toxicity nor symptoms of opioid withdrawal during methadone wean. We suggest that methadone is safe and has some clinical benefit, which should be proven in prospective randomized trials for pediatric patients with SCD and chronic pain.     

The role of tumor lysis in reversible posterior leukoencephalopathy syndrome

We report on a child with B-cell lymphoma who developed hypertension and reversible posterior leukoencephalopathy syndrome (RPLS) after chemotherapy conducted during recovery from tumor lysis syndrome. After recovery from RPLS, the patient received further combination chemotherapy without recurrence of the neurological signs or symptoms suggestive of RPLS. Many etiological factors have been reported in the development of RPLS; however, little attention has been paid to tumor lysis syndrome as a contributory factor for RPLS. Tumor lysis syndrome can precipitate the development of RPLS in patients with hematological malignancies who are undergoing chemotherapy. Knowledge and awareness would help facilitate immediate management such as normalization of blood pressure and temporary cessation of chemotherapy, helping to avoid irreversible brain damage.     

HODGKIN'S DISEASE IN A CHILD WITH SICKLE CELL DISEASE TREATED WITH HYDROXYUREA

Hydroxyurea (HU) is an oral drug that ameliorates the clinical course of sickle cell anemia by &#175 increasing the levels of fetal hemoglobin and decreasing the adhesion of red cells to endothelium. Although HU has minimal short-term toxicity, few data are available about the long-term safety and the potential risk for carcinogenesis or leukemogenesis. An 8-year-old child with sickle cell / &#103 0- thalassemia who received HU treatment for painful crises is described. Six months after the initiation of the HU treatment he developed Hodgkin's disease, lymphocyte predominance subtype. Chemotherapy induced a complete remission. After discontinuation of chemotherapy the painful crises recurred and bone marrow transplantation was decided at the age of 12 years. Two years after the bone marrow transplantation, the child is in complete remission without painful crises. Although the authors suggest that the development of Hodgkin's disease is a coexisting event, questions arise about the safety of HU treatment in childhood.     

A comparison of two transfusion regimens in the perioperative management of children with sickle cell disease undergoing adenotonsillectomy

Adenotonsillar hypertrophy and chronic tonsillitis are common findings in patients with sickle cell disease (SCD). Various preoperative transfusion regimens have been suggested to reduce the population of sickle erythrocytes and correct the anemia, ranging from conservative (correcting the anemia) to aggressive (lowering the level of HbS to less than 30%). A total of 39 patients with SCD were included in the study. They were divided into 2 groups. Fourteen patients in group 1 were assigned aggressive exchange transfusion and 25 patients in group 2 were assigned a conservative (simple) transfusion. The 2 groups were compared for possible operative and postoperative complications. Thirty percent of patients in both groups had postoperative complications. They ranged from mild local infection to acute chest syndrome. Simple transfusion was not associated with higher incidence of complications and resulted in only one-third as many transfusion requirements.     

Hemoglobin A1c and fructosamine correlate in a patient with sickle cell disease and diabetes on chronic transfusion therapy

In patients with sickle cell disease (SCD) and diabetes mellitus (DM), hemoglobin A_1c (HbA_1c) is unreliable and the American Diabetes Association recommends monitoring long‐term glycemia by measuring serum glucose, but use of serum fructosamine (SF), a measurement independent of red cell lifespan, has been reported. SF as a screen for DM in SCD, however, is not standardized and its relationship to serum glucose has not been validated. Further, screening for DM was not adequately addressed in the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines for SCD management. Blood transfusions, an important treatment for some patients with SCD, can also impact HbA_1c. We present a case of a patient with SCD and cystic fibrosis‐related diabetes on monthly chronic transfusions therapy (CTT) who had well‐correlated “steady state” HbA_1c and SF levels over time, suggesting for the first time these markers may actually be useful when following long‐term glycemic control in patients with SCD on CTT programs.     

Splenic complications of the sickling syndromes and the role of splenectomy.

PURPOSE: To analyze the authors' experience with splenectomy for sickling disorders and evaluate the indications, complications, and outcome. PATIENTS AND METHODS: Over a period of 10 years (1987-1997), 113 patients with sickling disorders (100 with sickle cell disease and 13 with sickle-beta-thalassemia) had splenectomy at the authors' hospital as part of their management. The indications for splenectomy were hypersplenism (26 patients), major splenic sequestration crisis (MSSC) (23 patients), minor recurrent splenic sequestration crisis (MRSSC) (50 patients), splenic abscess (12 patients), and massive splenic infarction (2 patients). RESULTS: Splenectomy in patients with sickle cell disease (SCD) and sickle-beta-thalassemia (S-beta-Thal) was beneficial in reducing their transfusion requirements and its attendant risks, eliminating the discomfort from mechanical pressure of the enlarged spleen, and avoiding the risks of acute splenic sequestration crisis. It also was curative for patients with splenic abscess and massive splenic infarction. Twenty-four patients with SCD (24%) had splenectomy and cholecystectomy caused by concomitant gallstones. There was no mortality, and the postoperative morbidity was 7%. CONCLUSIONS: With careful perioperative management, splenectomy is both safe and beneficial in a select group of patients with SCD and S-beta-Thal.