Childhood Cancer

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Hodgkin Lymphoma

Hodgkin lymphoma is a type of lymphoma defined by the presence of a specific type of cancerous cell called Reed-Sternberg cells. Like all lymphomas, Hodgkin lymphoma originates in the lymphatic system. 

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Latest Hodgkin Lymphoma grants

Sumit Gupta, MD, PhD, Principal Investigator
Hospital for Sick Children
Young Investigator Grants, Awarded 2015
Jean Nakamura, Principal Investigator
University of California San Francisco
Young Investigator Grants, Awarded 2011

Latest Hodgkin Lymphoma blog posts

July 9, 2018

by Trish Adkins

In 2000, the first draft of the map of human genome—a mosaic representation of characteristics of what makes our biology uniquely human—was released. The map paved the way for more genomics research in several fields ranging from human biology to agriculture and gave scientists models of genetically normal cells which they could compare to abnormal cells, like those cells that make childhood cancer so deadly.

Now, in 2018, an ALSF funded-research project has resulted in the release of over 270 genetic sequences of 25 different types of childhood cancer used routinely by the National Cancer Institute’s Pediatric Preclinical Testing Consortium (PPTC). Each unique tumor model and its biological characteristic data is available to all academically qualified petitioners—opening the door for breakthroughs in childhood cancer research.

Keep reading to learn how cures are getting closer, one childhood cancer genome at a time. 

The story behind the 270 models begins with the PPTC

Founded in 2015 and funded by the National Cancer Institute, the consortium works to develop reliable preclinical testing data for potential pediatric cancer drugs. There are hundreds, maybe thousands of potential cancer drugs—making the study of each drug in a pediatric clinical trial impossible. The PPTC narrows down the list, providing researchers with reliable drug effectiveness data that they can use to accelerate research from “bench to bedside;” bringing science out of the lab and into the clinic. The models studied are directly derived from childhood cancers at diagnosis or relapse, and thus are directly representative of the types of cancers treated in clinical trials.

However, while there is a large pool of potential drugs, there was not a large pool of accurate pediatric tumor models for which to test the drugs. This has long been a struggle for the pediatric oncology research community. Over 14.1 million people are diagnosed with cancer each year worldwide, but only 250,000 of those cases are pediatric cancer. The pool of potential tumors to model is small and obtaining viable tumor cells is difficult, especially for some types of pediatric cancers like spinal cord tumors where securing tissue samples is tricky because of the tumor’s location. 

The PPTC had an idea for a new major effort, the Pediatric Preclinical Genomic Characterization Project, which sought to characterize the tumor samples being used in drug testing. These patient-derived xenograft (PDX) childhood cancer models were being used routinely, but the majority did not have detailed genetic data available. 

The potential was enormous: with a critical mass of PDX models made available to the scientific community, the PPTC could accelerate the route to clinical trials much more rapidly than ever before, bringing potentially lifesaving treatment to children waiting desperately for cures.

There was one catch: there was no funding available for a PDX sequencing project. That’s when ALSF entered the picture. 

The Foundation learned about the PPTC and its desire to generate high-quality PDX genetic data to streamline science’s understanding of why novel treatments work in some cases, but do not work in others, and immediately recognized its promise. 

“ALSF has a legacy of filling critical research and family services gaps in the childhood cancer community,” said Liz Scott, Co-Executive Director of ALSF.  “We knew that funding the PPTC’s genomic sequencing project had the potential to spark long-lasting impact, collaborative efforts and ultimately advance the pace of finding cures for all kids with cancer.”

Legacies of Hope
With the ALSF funding, the PPTC could characterize the stored samples that had been donated by children battling pediatric cancer. Some donations came while a child was in treatment, with an institution’s requested permission to use extra tumor tissue that was not needed for diagnosis or treatment protocol, for research.  

Other donations came from families eager to find cures even when it was too late for their own child. These profound gifts, given at the time of death, left behind a legacy of hope waiting to be unlocked.  

The PPTC has access to over 400 samples representing 25 different types of childhood cancer, stored at -80℃ in its five locations at institutions in the United States and also in Australia, and continues to generate more, often in collaboration with Dr. Patrick Reynolds who receives ALSF funding for the Childhood Cancer Repository where many genetic models are generated. The vast majority of the samples represent relapsed disease and have the promise of modeling childhood cancers at the time that many new investigational treatments are tried in the clinic in Phase 1 trials.

While the PPTC could have tried to establish the tumor lines in a test tube or dish, the researchers leading the project knew from prior experience that growing tumors in artificial environments could lead to the generation of different mutations in revolt to their new homes. These mutations would lead to inauthentic cell lines and muddy the search for drugs that could work. 


Accelerating the Clinical Trial Process
Bringing the right drugs to the clinic has long been a struggle for pediatric oncology researchers.  

The first priority is to ensure a patient’s safety in a clinical trial by adhering to specific safeguards before the trial begins and during the trial. But a safe drug is not necessarily effective and can offer false hope to patients who are enrolled in clinical trials after one relapse—or several.  

Using the PDX models, researchers could discover the “good drugs”—the drugs most likely to be safe and effective in killing cancer cells, and also discover the “bad drugs”—those that are not effective and those that might even result in resistant disease.

The models also give researchers the opportunity to continue to move away from treating diseases by name and begin treating the specific genetic lesions that might drive cancer growth. It is the literal meaning of “killing two birds with one stone”— two different types of cancers may share a genetic trait and in turn, could be sensitive to the same drug. 

“With good models, we can begin designing experiments more robustly and begin getting the right drugs to the clinic and to children quickly,” said Dr. John Maris, MD, of ALSF’s Scientific Advisory Board and Children’s Hospital of Philadelphia’s neuroblastoma representative in the PPTC.

ALSF’s contribution allowed the PPTC, in collaboration with Baylor College of Medicine and Nationwide Children’s Hospital (led by David Wheeler and Julie Gastier-Foster), to genomically characterize over 270 PDX models with four different genomic tools—each tool giving researchers more clues to how the genes and proteins drive cancer growth.

Researchers worked to filter out any noise or irregularities in the final data, using existing cancer cell knowledge and past research. They have ensured the models matched their cells of origin and have retained known cancer driver mutations over time. 

The PPTC began using the data immediately—fulfilling its mission of matching drugs to genetic targets and testing in advance of human clinical trials. 

Now, eighteen months after the PPTC commenced the PDX project, other scientists now have the same opportunity. The data, which was released on July 9, 2018, is available to all academically qualified petitioners through the PedcBioPortal for Childhood Cancer Genomics (pedcBio portal). Raw characterization data will be available on the database of Genotypes and Phenotypes (dbGaP) in the coming months. Tissue samples will be available by request—for just the cost of postage to ship. 

“When childhood cancer relapses, it can become lethal,” said Dr. Maris. “But today, the scientific community has open access to deep genetic profiling that will help overcome some of the major problems we have when treating childhood cancer. We’ve now accelerated years ahead in our search for cures.”

Read more about the PPTC project, as well as other innovative ALSF research here. 

April 20, 2018

by Trish Adkins

Childhood lymphoma arises from the immune system cells and occurs when those cells grow in an uncontrolled and uncoordinated way. While it shares some similarities with leukemia, lymphoma often settles in the lymph nodes of the body, instead of in the bloodstream.

Each type of lymphoma is named by its cell of origin and this dictates treatment protocol. The good news: the most common types of lymphoma (Hodgkin, Non-Hodgkin, Burkitt) have relatively high cure rates as compared to other types of childhood cancer.  

The bad news: cure rates are not 100-percent and even those children who are cured of primary lymphoma can face a lifetime of side effects including cardiac dysfunction and even secondary cancers. 

But, there is hope on the horizon. Alex’s Lemonade Stand Foundation (ALSF) funded researchers so they could continue to search for safer treatments and cures for children battling lymphoma. Meet some of these childhood cancer heroes and the researchers making a difference every day:

Miracle Cure: Zach

When Zach was 5 years old, he was diagnosed with anaplastic large cell lymphoma (ALCL), an extremely rare type of non-Hodgkin lymphoma. While still in treatment, Zach’s lymphoma relapsed. As Zach became sicker and his prognosis worsened, his parents felt they were out of options. Traditional chemotherapy was not working and, in fact, was making Zach sicker. Zach was running out of time. 

Zach’s lymphoma tested positive for ALK, an abnormal gene that fuels certain types of cancer. ALSF-funded research made a clinical trial for a new drug possible, bringing hope to his family. This drug, known as crizotinib, targets and turns off the ALK gene. Days after taking the drug, Zach was feeling better and his cancer was disappearing. 

Now Zach is 12 years old and cancer-free. 

Breakthrough Research: Dr. Yael Mosse, Children’s Hospital of Philadelphia 

Funded by an ALSF Reach grant, Dr. Yael Mosse led the research team at Children’s Hospital of Philadelphia that made Zach’s treatment possible. Her team theorized that since crizotinib worked in ALK-positive lung cancer in adults, it could be the hope children battling ALK-positive cancer needed. 

And since crizotinib is a targeted therapy that just attacks one gene, it has fewer side effects as compared to chemotherapy. 

Dr. Mosse’s clinical trial enrolled 30 children--including Zach. Zach was seven out of the eight children with the same type of lymphoma that received the same miraculous cure. The trial also tested crizotinib in children battling ALK-positive neuroblastoma with successful results. 

Hero (and Boss Lady) Sydnie 

The day Sydnie, age 13, was diagnosed with Hodgkin lymphoma she cried for a moment and then decided no one else was allowed to cry in front of her.

Then, Sydnie asked her mom to dye her blonde hair purple, pink and blue—because she knew she was going to lose it anyway. When she lost her hair as a result of chemotherapy, she wanted to shave her head right away because, as Sydnie, declared, cancer was not going to determine if she was bald or not. It was up to her.

“I won’t let cancer be the boss of me,” Sydnie said. 

Hodgkin lymphoma has a relatively high cure rate (80-90% in most cases) but requires immediate chemotherapy and radiation. Sydnie endured nine months of chemotherapy and 10 days of radiation. 

Today, she is cancer-free.
 
Translating Research into Treatments: Dr. Helen Heslop, Baylor College of Medicine 

Dr. Helen Heslop, a researcher at Baylor College of Medicine (an ALSF Center of Excellence) and Texas Children's Hospital focuses her work on translational research, which combines testing in the lab with patient studies. This type of research can help accelerate new therapies to clinical trials and someday, as new standards of care. Of particular interest to Dr. Heslop is how immunotherapy treatments, like CAR T cell immunotherapy, could help children with hard-to-treat lymphoma and also lead to safer frontline treatments. 
 
“The grants that ALSF provides support early career research, innovative, high-risk ideas and early phase trials that are critical for clinicians and scientists as they test approaches to improve outcomes,” said Dr. Heslop. 
 
Learn about lymphoma research and meet more childhood cancer heroes, here

December 1, 2017

by Adam Paris, ALSF

John Szigety was diagnosed at age 10 with Hodgkin lymphoma and underwent treatment at Memorial Sloan Kettering Hospital and Hackensack University Medical Center. After eight months of treatment, he suffered a relapse in early 2006, but completed treatment that June. Today, he is 11 years cancer-free. 

Amjad Shaikh was diagnosed just before his 9th birthday with leukemia and went through his entire treatment schedule at Children’s Hospital of Philadelphia (CHOP) for four years, before entering remission. Today, he is cancer-free. Amjad Shaikh

Both are childhood cancer survivors and medical school students who participated in Alex’s Lemonade Stand Foundation’s (ALSF) Pediatric Oncology Student Training (POST) grant program this past summer. They each felt the immense pride of being able to give back and help kids fight for their lives just like they did. They talked about the experience of beating cancer as kids and now, as researchers, searching for a cure.

Can you describe your work this summer as a POST student?
John Szigety (JS): I was looking at the effect of a drug on tumor progression and cell replication. The doctor I worked with at CHOP, Dr. Sarah Tasian, was investigating how to treat cancers with a specific mutation that makes the disease especially aggressive.
Amjad Shaikh (AS): I looked at CHOP and found an opportunity to study pediatric leukemia. I worked on studying mortalities associated with hospital characteristics and what a hospital can do to improve treatments or survival rates in kids fighting the same kind of cancer that I did.

 

Pictured: Amjad Shaikh

What was most meaningful about this experience?
JS: It was meaningful to see the different roles that a pediatric oncologist plays. As a patient, I only saw my oncologist, Dr. Steven Halpern, as a clinician. Dr. Tasian showed me how big of a role research plays in her life as a physician. That was new information to me.
AS: Part of it was that I got to see a lot of pediatric patients. The fact that I was on the other side and I understood from a clinical and medical level what was going on, I felt that maybe given a couple years I could be the person who was helping them out.

Was there a particular individual who inspired you to pursue pediatric oncology? 
JS: Dr. Halpern. When I was feeling miserable or having a bad day, he was receptive to me about how to change my regimen to make it more manageable. He would stop in my room during treatment to say hello or play board games. The cliché is that he treated me like a person and not an illness, but it's true. He's a big reason why I want to go into this field.
AS: My oncologist, Dr. Stephen Grupp. A few years after treatment, he told me he had been diagnosed with cancer and was undergoing treatment. It was a bit shocking because I had never seen an adult go through chemo. It left an impression that despite the fact he was going through chemo, and knowing what that was like, he still came in and treated kids. That meant a lot to me. It guided my philosophy in med school and framed my outlook for how a doctor should be. 

What did this POST opportunity and the chance to help other kids fight cancer mean to you?
JS: It was an honor. Since my diagnosis, I have wanted to help children affected by cancer. I've worked at Camp Kesem (summer camps hosted for kids whose parents have cancer), fundraised for various charities and pursued an education that brought me to medical school. The POST grant helped me contribute in another important way by investigating potential new treatments. While I didn't cure cancer or even come close, I am proud to say that I helped.
AS: It meant the world. Seeing Dr. Grupp and the team of physicians at CHOP, that’s my vision for the kind of doctor I’d like to be. 

As someone who survived childhood cancer, what does ALSF represent to you?
JS: In a word, ALSF represents hope. By supporting research across the country, ALSF represents the future of medical treatments and all the advances that are yet to come. 
AS: I think it’s a great organization for helping to develop a new generation of physicians and researchers who are going to continue these advancements. 

What are your goals and aspirations going forward?
JS: My goals are to become a pediatric oncologist and help treat children who have to fight for their lives. As a survivor, I have an understanding of how these pediatric cancer patients feel and I hope to help my future patients through the frightening and overwhelming experience of battling cancer.
AS: Especially after this summer I’m definitely set on a career in oncology. I’m not 100% sure how I want to go about it, since I'm still exploring all the specialties, but pediatric oncology is at the top of my list.

Each year, ALSF provides grants opportunities to medical students through the POST grant program. Read more about our POST grants here.