Professor Xue Yao: When is the Best Time for Children with Acute Lymphoblastic Leukemia to Return to School?

Professor Xue Yao: When is the Best Time for Children with Acute Lymphoblastic Leukemia to Return to School?

Source: Sunflower Children  

Author: Sunflower Children  

Editor: Wuxiu  

Date: December 1, 2023  

Disclaimer:  

This online Q&A is not a treatment recommendation. Due to the inability to understand the patient's detailed condition and provide an in-person diagnosis, expert opinions are for reference only. For specific treatment plans, please visit a formal hospital.  

In this edition of the "Expert Q&A" column, we invite Director Xue Yao from the Hematology Oncology Department of Nanjing Children's Hospital to answer your questions.

01  

Q: A 15-year-old boy was diagnosed with intermediate-risk acute B lymphoblastic leukemia L1 in March 2023, at the age of 14 years and 9 months. He is currently undergoing treatment.  

I would like to ask:  

(1) Is the Mll-AF9 fusion gene prognosis poor?  

(2) Is the relapse rate for older children higher than for those under 10?  

(3) If he goes back to school, when is the best time for him to return?

A: (1) The Mll-AF9 fusion gene is associated with a poor prognosis. We are currently following an intermediate-risk treatment plan. (2) Children over 10 years old have an elevated risk, so their risk level should be considered at least intermediate. (3) Generally, children can gradually return to school during the maintenance phase, particularly in the last year of treatment, but it's essential to assess their immune function.

02  

Q: An 8-year-old boy was diagnosed with acute T lymphoblastic leukemia L2 in August 2021 and has completed treatment. Initial tests showed the fusion gene SlL-TAL1 positive, with three mutations and three significant clones suitable for Sep-MRD tracking. After 30 days, MRD was zero; the fusion gene and mutations turned negative after 52 days; three clones are unstable, with two instances of zero, and the latest result on September 28, 2023, was negative six.  

I would like to ask:  

(1) Given the unstable clones, he has taken Dasatinib during maintenance; does he need to continue after completing treatment? If so, for how long?  

(2) Does the presence of unresolved clones indicate a higher risk of relapse?  

(3) After completing treatment, does he still need to track minimal residual disease?

A: (1) Dasatinib can be extended for another 3 to 6 months. If residual disease is negative, treatment can be stopped. (2) Theoretically, if clone monitoring shows residual positivity, the risk of relapse is increased in the later stages. (3) In acute lymphoblastic leukemia, monitoring clones for residual disease is highly sensitive, but currently, there is no clear treatment adjustment based on clone monitoring. If clones remain positive after treatment, continued tracking is recommended (usually every 3 to 6 months) to adjust future monitoring intervals based on residual clone results.

03  

Q: A 6-year-old boy was diagnosed with high-risk acute B lymphoblastic leukemia L2 at the age of 5 and is currently undergoing treatment.  

On January 29, 2022, the report indicated 51 types of fusion gene qualitative analysis, with BCR-ABL1 (p190) positive. After targeted therapy, the gene turned negative, and he continued taking Dasatinib.  

During the first treatment, he had gastrointestinal bleeding and went to the ICU; in the second treatment, he had gastrointestinal bleeding again and did not undergo CAM, including COAD; in the third treatment, he experienced large-dose toxicity and went to the ICU. This year, on August 16, during the fourth treatment, he had gastrointestinal bleeding (the third instance, possibly related to the targeted drug) and was on Belinostat for half a month, but the fourth treatment has yet to start.  

On October 6, 2023, he had a fever of 38.4, vomiting, and loss of appetite. Tests showed Norovirus, parainfluenza virus, and Mycoplasma pneumonia positive (previously positive but later negative). On October 16, he went for VDLD (having stayed in the hospital for more than ten days after gastrointestinal bleeding on August 18, and after discharge, he took Belinostat for 14 days, fearing he would not tolerate additional medication, thus delaying treatment for two months). On October 17, he was discharged but continued to experience nausea. An ultrasound and echocardiogram showed significant gas buildup, and abdominal massages were ineffective. He frequently consulted gastroenterology and hematology, taking probiotics, compounded proteases, omeprazole, fluid replacement, and Domperidone. Yesterday, he received fluid replacement with Vitamin B6 and switched to Maizilin, discontinuing omeprazole. He vomited less and managed to eat a bit, but his weight has dropped by 8 pounds since the fever began, and he is lethargic.  

I would like to ask:  

(1) After missing a large CAM, two COADs, and two large doses, combined with the positive fusion gene p190, should these treatments be compensated later?  

(2) Given the gastrointestinal bleeding has delayed treatment, will this impact prognosis? Would additional doses of Belinostat improve prognosis?  

(3) Currently experiencing loss of appetite, vomiting, and weight loss, what treatment should he receive?

A: (1) The treatments missed are relatively important in pediatric ALL chemotherapy, so it is advisable to compensate for them in subsequent treatment cycles. (2) During gastrointestinal bleeding, the child's tolerance is poor, preventing further chemotherapy. Short-term delays in treatment may not significantly affect overall prognosis, but if delays are prolonged and repeated, it may be beneficial to add Belinostat to achieve deep remission while avoiding drug side effects. During this time, regular lumbar punctures should be done to prevent central nervous system leukemia. (3) The current lack of appetite and vomiting is likely related to damage to the child's gastrointestinal mucosa, which has not completely healed after multiple bleeds, leading to reduced digestive absorption. There is no specific treatment; the current use of probiotics, anti-acid and anti-emetic medications, and dietary adjustments focusing on high-quality protein are recommended, along with ongoing assessments.

04  

Q: A 5-year-old boy was diagnosed with intermediate-risk acute B lymphoblastic leukemia (ETV6/RUNX1 positive) at the age of 4 and has just completed his second high-dose treatment. Initial screening on July 8 was positive, with CD38 at 0.81% on July 29; on September 4, CD38 was 0.01%, ETV6/RUNXI positive, and ETV6/RUNXI/ABL1 at 0.01%; on September 25, CD38 was 0.005%.  

I would like to ask:  

(1) Given the current situation, should we perform a 10 to the negative 6 monitoring? Under what circumstances can Belinostat be considered?  

(2) During high-dose treatment while taking Mercaptopurine, can he also take White Blood Cell Booster and Ubenimex? If both medications are taken simultaneously and white blood cells remain stable between 2-3, and granulocytes between 1-2, what would happen if this is not allowed? Would it affect prognosis and relapse probabilities?

A: (1) Currently, it seems the child's MRD residual disease has not completely turned negative. Generally, for children who have undergone several cycles of conventional chemotherapy and still show residual positivity, it is advisable to add Belinostat or CD19 CAR-T treatment to achieve deep molecular remission. (2) It is permissible to take both medications together. White blood cell levels between 2-3 and granulocytes between 1-2 are acceptable, and continuous dynamic monitoring is recommended.

05  

Q: A 6-year-old boy was diagnosed with low-risk acute B lymphoblastic leukemia at the age of 5 and is currently in interim treatment.  

The child received two rounds of Asparaginase, and after the last injection on October 1, his amylase levels were high. On the 2nd, it was 184; he was treated with Octreotide and Omeprazole intravenously. On the 3rd, it was 140, and treatment continued; on the 5th, it was 187, and on the 6th, while continuing medication, it rose to 445. He then started fasting and underwent CT and enhanced CT scans, both showing a normal pancreas. However, the indices have been fluctuating; on the 25th, it was over 200, and on the 27th, it was 166.  

I would like to ask:  

(1) What impact does fluctuating amylase levels have on the child? Is there a risk of pancreatitis?  

(2) For the next phase of treatment, if the doctor suggests reducing one dose of Asparaginase, will this affect the prognosis?

A: (1) Elevated amylase levels indicate mild pancreatic damage, and there is still a risk of pancreatitis. Close monitoring for abdominal pain, vomiting, and other symptoms is necessary, along with ongoing observation of amylase changes and abdominal ultrasounds or CT scans. A light diet should be maintained. (2) Reducing Asparaginase treatment may have some impact on prognosis. If the child's amylase levels return to normal without clear signs of pancreatitis, treatment with Asparaginase should not be halted, and it may be possible to resume in the future under the protection of Octreotide.

If you have many questions, you can find answers through the following two avenues:  

1. [WeChat] — Search for the "Sunflower Children" mini-program. After entering the program, you can use the search function to obtain comprehensive information.  

2. If you don't find your ideal answer in the mini-program, you can also ask the experts for consultation. We will do our best to have doctors respond within a week and publish the answers.  

Column Editor: Zhu Qijing  

Layout: Xia Yu  

Proofread: Jiang Jiang