Safety and efficacy of a dose-dense short-term therapy in patients with MYC-translocated aggressive lymphoma.

Patients with aggressive B-cell lymphoma and MYC rearrangement at fluorescence in situ hybridization exhibit poor outcome after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In the last decade, 68 patients with Burkitt lymphoma ([BL] n = 46) or high-grade B-cell lymphoma ([HGBCL] single, double, or triple hit; n = 22) were treated with a dose-dense, short-term therapy termed "CARMEN regimen" at 5 Italian centers. Forty-six (68%) patients were HIV+. CARMEN included a 36-day induction with sequential, single weekly doses of cyclophosphamide, vincristine, rituximab, methotrexate, etoposide, and doxorubicin plus intrathecal chemotherapy, followed by high-dose-cytarabine-based consolidation. Patients who did not achieve complete remission (CR) after induction received BEAM (carmustina, etoposide, cytarabine, melfalan)-conditioned autologous stem cell transplantation (ASCT) after consolidation. Sixty-one (90%) patients completed induction, and 59 (87%) completed consolidation. Seventeen patients received ASCT. Grade 4 hematological toxicity was common but did not cause treatment discontinuation; grade 4 nonhematological toxicity was recorded in 11 (16%) patients, with grade 4 infections in 6 (9%). Six (9%) patients died of toxicity (sepsis in 4, COVID-19, acute respiratory distress syndrome). CR rate after the whole treatment was 73% (95% confidence interval [CI], 55% to 91%) for patients with HGBCL and 78% (95% CI, 66% to 90%) for patients with BL. At a median follow-up of 65 (interquartile range, 40-109) months, 48 patients remain event free, with a 5-year progression-free survival of 63% (95% CI, 58% to 68%) for HGBCL and 72% (95% CI, 71% to 73%) for BL, with a 5-year overall survival (OS) of 63% (95% CI, 58% to 68%) and 76% (95% CI, 75% to 77%), respectively. HIV seropositivity did not have a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas.

The diagnostic dilemma of idiopathic intracranial hypertension in a child with acute lymphoblastic leukemia: COVID-19 or cytosine arabinoside?

BACKGROUND: Idiopathic intracranial hypertension is a rare neurological condition among children. Its manifestations vary from mild headaches to loss of vision. Although rare, COVID-19 infection and high dose cytosine arabinoside have been reported as risk factors for this neurological disorder. In patients with acute leukemia, idiopathic intracranial hypertension diagnosis is simple, but finding its etiology can be difficult. CASE PRESENTATION: We report a case of a 9-year-old boy with an ongoing treatment for T-acute lymphoblastic leukemia presenting with persistent headaches and diplopia. A diagnosis of idiopathic intracranial hypertension was retained based on clinical, imaging and laboratory findings. Due to its rarity, we describe its clinical and therapeutic features and highlight the challenging etiological dilemma between COVID-19 infection and high dose cytosine arabinoside administration. CONCLUSION: Persistent headache in a pediatric patient with leukemia can be due to many neurological disorders other than leukemic relapse. Given the improvement of the neurological symptoms after the SARS-CoV-2 PCR negativization and the successful re-introduction of high dose cytosine Arabinoside, the diagnosis of idiopathic intracranial hypertension associated with Covid-19 infection was withheld.

Severe COVID-19 virus reactivation following treatment for B cell acute lymphoblastic leukemia.

SARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib. She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge. After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June. She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later. Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.