The influence of traumatic lumbar puncture and timing of intrathecal therapy on outcome of pediatric acute lymphoblastic leukemia

The CNS is a frequent site of relapse of childhood acute lymphoblastic leukemia (ALL). Traumatic lumbar puncture (TLP) is thought to increase the risk of CNS relapse. The authors examined whether TLP at the time of diagnosis affected outcome and whether this effect was influenced by the timing of intrathecal therapy (IT) in 77 patients with newly diagnosed ALL. IT was instilled at the time of either the diagnostic LP (early) or a second LP 24-48 h later (delayed). Of the 19 patients who had a TLP at diagnosis and received late IT therapy, 6 had isolated CNS relapse and 2 had combined CNS and bone marrow (BM) relapse. Of the 9 patients who had TLP and received early IT therapy, 1 had a CNS relapse (p = .20). In an analysis stratified according to risk of relapse, the odds ratio (OR) for relapse was 0.8 among patients at low and standard risk who had delayed IT therapy after TLP (p = .99) vs. 0.17 for those who had early IT (p = .47). Importantly, among patients with high-risk ALL, the OR for relapse was 21.0 for delayed IT therapy (p = .09) and only 1.5 for early IT therapy after TLP (p = .99). The results indicate that TLP at diagnosis appears to increase the risk of CNS relapse markedly in patients with high-risk ALL, and the use of early IT therapy appears to reduce this risk. These findings need to be confirmed by prospective, randomized studies.     

Intracerebral hematoma as a complication of intrathecal methotrexate administration

Neurotoxicity of methotrexate is a well-documented issue, but development of an intracerebral hematoma following administration of intrathecal methotrexate is an extremely rare entity. A 6-year-old male with the diagnosis of non-Hodgkin lymphoma was put on a treatment regimen, including intrathecal methotrexate. Six days following the last intrathecal methotrexate administration, the patient developed a deteriorating state of consciousness. There was no history of trauma. Coagulation studies and platelet count were normal. Magnetic resonance imaging of the brain demonstrated a large left frontoparietal hematoma. Intracerebral hematoma may be a very rare, but serious, complication of intrathecal methotrexate administration.     

Use of recombinant factor VIIa prior to lumbar puncture in pediatric patients with acute leukemia

The persistence of abnormal coagulation test results after standard treatment with fresh frozen plasma (FFP) poses significant problems in children with acute leukemia requiring a diagnostic lumbar puncture and intrathecal chemotherapy. We report the prophylactic use of a single dose of 90 microg/kg recombinant activated factor VII (rFVIIa) in three children and the rapid correction of abnormal coagulation test results previously not corrected by FFP. Administration of rFVIIa was useful in avoiding a delay of diagnostic lumbar punctures and intrathecal chemotherapy. Hemorrhagic complications and adverse effects of rFVIIa were not observed. Prospective evaluation of this indication and dose appears warranted. (c) 2005 Wiley-Liss, Inc.     

Discitis following lumbar puncture in non-Hodgkin lymphoma

Discitis in children is a rare disorder of intervertebral disc and vertebral end plate. Infection or trauma, like lumbar puncture, may be the possible causes. Low-back pain and gait disturbance are the main symptoms. The most appropriate diagnostic procedure is MRI. Treatment is mainly empirical. Here a case with non-Hodgkin lymphoma is discussed. Treatment consisted of strict bed rest and antibiotics. Safe and sterile technique is important in patients with invasive procedures like intrathecal chemotherapy. Although discitis is a self-healing condition, it might cause vertebral osteomyelitis. In this regard, physicians should be aware of this probable complication after lumbar puncture and manage it earlier in children with cancer.     

Successful treatment of acute lymphoblastic leukemia with L-asparaginase-induced intracranial hemorrhage to activated recombinant factor VIIa in a child

L-Asparaginase, a major component of therapy in children with acute lymphoblastic leukemia, has been shown to induce coagulopathy by inhibiting synthesis of clot-forming and clot-inhibitory proteins. The authors report the successful use of recombinant factor VIIa in a 15-year-old girl with acute lymphoblastic leukemia who had L-asparaginase-induced intracranial hemorrhage. The present case is the first to demonstrate use of rFVIIa in L-asparaginase-induced intracranial hemorrhage in a child with acute lymphoblastic leukemia.     

Extramedullary recurrence of acute lymphoblastic leukemia 15 years after initial diagnosis

We describe a 19-year-old man with recurrence of a lymphoid malignancy involving the ethmoid sinus 15 years following diagnosis and 10 years after discontinuation of therapy for childhood acute lymphoblastic leukemia (ALL). The cytologic appearance and immunologic phenotype of the tumor cells suggest that this malignancy represents a recurrence of his original tumor. Initial relapse of ALL is unusual after 4 years of continuous remission off therapy. This case illustrates that late relapse can occur and may present with unusual sites of involvement.     

Desensitization to pegaspargase in children with acute lymphoblastic leukemia and lymphoblastic lymphoma

Hypersensitivity to pegaspargase is associated with inferior survival in pediatric patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. In the past year, drug‐supply shortages have led to the lack of an available alternative to pegaspargase. Rather than omit asparaginase from the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma patients with hypersensitivity to pegaspargase, we continued pegaspargase treatments for nine pediatric patients, utilizing a rapid desensitization protocol. There were no adverse events related to the pegaspargase during desensitization, and all patients who were checked had asparaginase serum levels above the threshold of 0.1 IU/mL at 7 to 14 days after pegaspargase therapy.     

Acute lymphoblastic leukemia and lymphoblastic lymphoma in adolescents and young adults

Compared to younger and older age groups, the incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) has increased more in the adolescent and young adult (AYA) population, the cause of which is unknown. As of the last decade, only half of the AYA patients with these diseases were surviving 10 years. Strong evidence exists that favors “pediatric” treatment regimens for AYAs compared to “adult” treatment regimens in terms of survival rates, hospitalization time, toxicities, late effects, and quality of life both during and after treatment. Targeted agents are clinically accessible for certain subsets of patients with Philadelphia‐like ALL, the incidence of which peaks in AYAs. Treatment teams must appreciate the complex psychosocial underpinnings in these patients in order to maximize compliance with the prolonged and complex treatment plans during the AYA years. 1     

NHL in adolescents and young adults: A unique population

Non‐Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid malignancies with high incidence in adolescents and young adults (AYAs). The most common diseases include diffuse large B‐cell lymphoma, anaplastic large cell lymphoma, Burkitt lymphoma, lymphoblastic lymphoma, and primary mediastinal large B‐cell lymphoma. In comparison to younger children and adults, AYAs (15–39 years) with NHL present a specific set of challenges including variations in tumor biology, inconsistent treatment, pharmacodynamics, and psychosocial barriers. While survival of AYAs with NHL has improved, cure rates remain suboptimal. Incorporation of novel agents into pediatric‐inspired treatment regimens specifically designed for NHL in AYAs has led to improved outcomes. Consideration of AYAs as a distinct population in the diagnosis and treatment of NHL is encouraged.     

Incidence of bacteremias and invasive mycoses in children with acute non‐lymphoblastic leukemia: Results from a multi‐center Italian study

Background

Data on the epidemiology of bacteremias and invasive fungal diseases (IFD) in children with acute myeloid leukemia (AML) are scarce.

Design and Methods

In a multi‐center, retrospective study, we analyzed proportion, rate per 1,000 person‐days at risk, and cumulative risk of bacteremias and IFD in children with AML.

Results

Between January 1998 and December 2005, 240 children were treated for AML at 8 Italian Centers, for a total of 521 treatment courses and 63,232 person‐days at risk. Bacteremia was observed in 32% of treatment courses and IFD was seen in 10% (P < 0.0001), with rates of 2.62 and 0.84, respectively (P < 0.001). There was a significantly higher frequency of IFD during relapse treatment: proportion 15% versus 9% (P = 0.05), rate 2.10 versus 0.64 (P = 0.008) and cumulative risk 32% versus 12% (P = 0.007), while there were no differences in the proportion, rate and cumulative risk of bacteremia during front‐line or relapse treatment. The epidemiology of bacteremias and IFD was different during front‐line therapy for M3 as compared to other types of AML, but the differences were not statistically significant.

Conclusions

Severe infectious complications are frequent during the treatment of pediatric AML, especially during relapse treatment, and bacteremias are more frequent than IFD. Pediatr Blood Cancer. 2010;55:1103–1107. © 2010 Wiley‐Liss, Inc.