Category Archives: Stem Cell Therapy

Despite being one of the most common forms of cancer, awareness of blood cancer pales in comparison to other types of the disease. In fact, according to Blood Cancer UK research, more than half of UK adults cannot name a single symptom of blood cancer.

Over the past two centuries, researchers have identified more than 100 different types of blood cancer, while most patients may be familiar with the big three (leukaemia, lymphoma, and melanoma). However, myelodysplastic syndromes and myeloproliferative neoplasms are also prominent types of blood cancer.

Thanks to the dedicated efforts of doctors, patients, carers, and healthcare professionals, people diagnosed with blood cancer are now living longer, with a steady stream of more effective treatments entering the market each year. However, there is still much to be done to achieve a vision wherein all those diagnosed with blood cancer survive.

As we enter Blood Cancer Awareness month, a global event dedicated to spotlighting and supporting efforts to improve awareness, detection, and treatment of blood cancer, we take a look back in celebration of the achievements and breakthroughs that paved the way for todays innovations.

1832 Discovery of Hodgkins and non-Hodgkins lymphoma

Although early accounts of an illness akin to leukaemia can be traced back to Ancient Greece, the first official description of blood cancer didnt appear until 1832, when British pathologist and pioneer of preventative medicine Thomas Hodgkin used the controversial concept of micrology to identify the abnormalities in the lymphatic system.

During his time working in the pathology museum at Guys Hospital in London, Hodgkin studied several preserved specimens of human organs affected by disease. Noticing a pattern in the lymph nodes and spleen that indicated the appearance of disease, he published his findings in a paper entitled, On Some Morbid Appearances of the Absorbent Glands and Spleen.

At the time, his hypothesis appeared to fall on deaf ears, and it would take a further three decades before Hodgkins discovery was recognised.

1844 First reported case of multiple myeloma

The first well-documented case of multiple myeloma was reported in 1844 by renowned British surgeon Samuel Solly. In 39-year-old patient Sarah Newbury, Solly observed the appearance of fatigue and bone pain resulting from multiple fractures. Only four years after the patient first showed symptoms, she died, and an autopsy revealed abnormalities in the bone marrow that closely matched the autopsy findings of 45-year-old Thomas Alexander McBean.

McBeans case is perhaps the most well-known account of multiple myeloma. Similar to Newbury, McBean known to be a highly respected tradesman developed fatigue and severe pain from weak and easily broken bones. After attempts to treat McBeans symptoms through cupping, applying leeches for maintenance therapy, and therapeutic phlebotomy proved unsuccessful, his physician, Dr Thomas Watson, prescribed steel and quinine, while a sample of his urine was sent to chemical pathologist Henry Bence Jones.

Following his death in 1846, histologic examination of McBeans bone marrow revealed a red gelatiniform substance consisting of nucleated cells, some twice the size of an average blood cell.

1847 Virchow links tumours and white blood cells

By the 1840s, histology (the study of microscopic anatomy) was a recognised discipline in the scientific community. Building upon early descriptions of leukaemia by French anatomist and surgeon Alfred-Armand-Louis-Marie Velpeau, in 1847, the father of modern pathology Dr Rudolf Virchow and English physician John Hughes Bennett independently observed abnormal increases in white blood cells in patients.

Virchow was the first to argue that cancer derives from changes in normal cells. Crucially, he observed a connection between certain tumours and inflammation, noting that neoplastic tissues were often covered with leukocytes of the immune system.

As with Hodgkins discovery, Virchows theory went almost unnoticed until the 20th century.

1907 The magic bullet of immunotherapy

In the early 1900s, researchers uncovered the existence of several types of blood cancer. However, effective treatments were not available at the time. During this period, Nobel prize-winning German scientist Paul Ehrlich developed his lock-key hypothesis of molecules that specifically bind to cell receptors.

Further research led Ehrlich to develop his side-chain theory, that antibodies produced by white blood cells act as receptors on the cell membrane. For his contribution, in 1908, Ehrlich received the Nobel Prize for Medicine in the field of immunology, together with the father of innate immunity, Ilia Metschnikow, whose discovery of phagocytosis formed the foundation of cell-mediated immunity.

While they may not have known it at the time, through their work Ehrlich and Metschnikow formed the cornerstone of modern immunology, including chemoreceptor and chemotherapy concepts that revolutionised blood cancer treatment over the following century.

1942 Chemotherapy moves from trenches to treatment

In the aftermath of World War I, medical researchers noticed that the mustard gas used to make chemical weapons for the battlefield also destroyed lymphatic tissue. Early experiments showed that topically applying nitrogen mustard caused tumours to shrink in mice.

Research into the medical potential of mustard gas stagnated until 1942, when two assistant professors at Yale, Louis S Goodman and Alfred Gilman, began to study the effects of nitrogen mustard on lymphoma. Although clinical trials proved that chemicals could be used to treat cancer, the results of the study remained a closely guarded military secret until 1946.

1956 The rise of bone marrow transplants

In a milestone achievement for blood cancer research and treatment, Dr E Donnall Thomas performed the first successful bone marrow transplant in 1956. The procedure involved transplanting bone marrow between identical twins, with tissue taken from the healthy twin given to the other who had leukaemia.

In 1968, the first bone marrow transplant using a matched donor took place at the University of Minnesota. Using a blood test developed by Dr Fritz Bach, Dr Robert Good determined that the patient, a baby with a severe immune deficiency, was a human leukocyte antigen match with his nine-year-old sister.

The ground-breaking approach to donor selection paved the way for future bone marrow transplants, including the first successful bone marrow transplant with unrelated patients in 1973.

Before the birth of bone marrow transplants, patients were often treated using chemotherapy, which could be used to kill cancer cells. However, this also presented a problem: chemotherapy does not discriminate between healthy and cancer cells, meaning that if patients were given sufficient doses to kill the disease, normal cells would also be harmed. With the advent of bone marrow transplantation, these healthy cells could be replaced with donor cells, allowing for higher doses of chemotherapy in treatment.

1980s Emergence of cord blood transplants

Another source of haematological stem cells emerged in the late 80s cord blood stem cells. The remaining blood found within the umbilical cord and placenta after birth is rich in blood-producing stem cells. Cord blood collection has rarely changed since the first successful procedure occurred in 1988.

Stem cells extracted from a donated cord can be frozen for a number of years and quickly accessed when needed. Once the transplant is complete, the cells will travel into the patients bone marrow, where they will begin to grow into normal blood cells.

Recognising the need to identify and match potential donors with patients, in 1989 the Bone Marrow Donors Worldwide programme was established.

Today, the bone marrow donor registry comprises more than 39,527,166 donors and 804,246 cord blood units.

2001 FDA green lights revolutionary treatments

Innovation in blood cancer treatments ushered in a new generation of targeted and precision treatments. One such therapy was Imatinib (also known as Gleevec or Glivec), a first-generation tyrosine kinase inhibitor dubbed a magical bullet, designed to specifically target BCR-ABL tyrosine kinase.

Just over a decade after it was developed by biochemist Nicholas Lyndon, Imatinib received US Food and Drug Administration (FDA) approval in 2001. Since then, it has transformed the treatment of chronic myeloid leukaemia and non-Hodgkins lymphoma.

The following year, the regulator also approved Rituximab, a monoclonal antibody targeting CD-20 positive B-cells, as a companion treatment of chemotherapy in older diffuse large B-cell lymphoma patients.

2002Emergence of CAR-T therapy

Building on the success of cytokine-based immunotherapies, scientists continued to seek other areas where the immune system could be leveraged against tumours. Throughout the 90s, Dr James Allison spearheaded research into T-cell engineering, a revolutionary technique that formed the foundation of chimeric antigen receptor (CAR) T-cell therapy.

Dr Allisons research into the function and application of T-cells in cancer treatment greatly broadened scientific understanding of the immune system. However, the first generation of CAR T-cells proved to be clinically ineffective.

It wasnt until 2002, when Memorial Sloane Kettering Cancer Center scientists Michel Sadelain, Renier Brentjens, and Isabelle Rivire opted to push the boundaries of research, by genetically engineering T-cells with a CAR, that the technique achieved successful results.

This research paved the way for the first successful treatment of a patient with acute lymphoblastic leukaemia in 2011.

2012 The 100,000 Genomics Project begins

Unlocking the secrets of the human genome has intrigued investigators for centuries. However, the technology needed to analyse genomic and long-term clinical data is a relatively recent development. With the launch of the 100,000 Genomes Project in 2012, an international team of researchers studied the role that genes play in health and disease.

For the first time, researchers demonstrated that whole genome sequencing could be used to uncover new diagnoses across the broadest range of rare diseases. This was an entirely new approach to DNA research. Previously, DNA would be segmented into short sections, which would then be read and sequenced separately.

The 100,000 Genomes Project sparked a new wave of research exploring the clinical potential of sequencing long strands of individual DNA without cutting them into sections. With this technique, it is hoped that researchers will gain previously inaccessible insights into cancer, revealing more accurate diagnoses and treatment pathways for patients.

20162022 New treatments enter the market

Over the past few years, the number of treatments approved for blood cancer has skyrocketed. Johnson & Johnsons Darzalex (daratumumab) was a notable development for the sector. The monoclonal antibody first received FDA approval in November 2015 as a monotherapy for patients with multiple myeloma, marking it as the first CD38-directed antibody to receive regulatory approval to treat the disease. It has since gone on to receive numerous approvals for multiple myeloma designations.

As of 2022, more than 800 new cell therapies are being developed for five blood cancers, with the market for oncology cell therapies expected to exceed $37 billion in value globally by 2028.

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Representative image.

Researchers from the School of Nanosciences and Molecular Medicine at Amrita Vishwa Vidyapeetham here have won a patent in the US and Australia for a novel nanomedicine that holds great promise for early detection and treatment of liver cirrhosis and liver tumour.

The invention is the outcome of a research project funded by the Nanobiotechnology Task Force of the Department of Biotechnology of the Government of India.

Shantikumar V. Nair and Manzoor Koyakutty from Amrita School of Nanosciences and Molecular Medicine in Kochi led a team to create a special type of nanomedicine that responds to radio wave signals sent from outside the body.

Once the nanoparticles are injected into a tumour, they can be heated up using external, medically approved radio waves. Doctors can visualise the tumour using an MRI machine and burn it off in a controlled manner.

Amrita researchers have demonstrated that the novel technology can be used for early detection of liver cirrhosis and liver tumour, early-stage image-guided treatment of liver tumours using radio-frequency ablation therapy as well as labelling and tracking the movement of stem cells inside the body after stem-cell transplantation to assess how effective the therapy has been.

Koyakutty said they had made a unique nanomedicine that can be used for medical imaging and drug delivery.

"Its particles are made of synthetically prepared calcium phosphate, a biomineral present in our bones. Generally, chemically prepared inorganic nanoparticles cause safety issues when used as nanomedicines. However, as a biomineral, calcium phosphate is biocompatible and biodegradable, hence totally safe for human use," said Koyakutty.

Shantikumar V. Nair said that they are currently investigating the cancer-immunotherapy application potential of these nanoparticles with the support of the Biotechnology Industry Research Assistance Council (BIRAC) and an Indo-Swiss collaboration with Ludwig Cancer Research Institute, University of Lausanne, and the University of Geneva, Switzerland.

"We are now testing regulatory safety studies in large animal models. We expect to conduct human trials of the nanomedicine within the next year," Nair said.

**

The above article has been published from a wire agency with minimal modifications to the headline and text.

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Kochi Scientists Win Patent for Novel Nanomedicine that Enables Early Liver Tumour, Cirrhosis Detection & Treatment - The Weather Channel

A review published in Frontiers in Oncology explored the application of allo-SCT for myelodysplastic syndromes and myeloproliferative neoplasms.

Myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs) are difficult to treat due to their varied clinical characteristics and prognostic heterogeneity. Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative treatment thus far, and a recent review in Frontiers in Oncology explored the application of and challenges associated with allo-SCT in this disease setting.

MDSs and MPNs are neoplastic hematological disorders, the most common of which is chronic myelomonocytic leukemia (CMML), a type of MPN. Both disorders lack specific molecular signatures and tend to show myelodysplastic and myeloproliferative features. Thus, these conditions are complicated to treat, and there is a lack of clear treatment guidelines or effective therapies to target them.

For patients with CMML, overall survival (OS) ranges from a few months to several years after diagnosis. Although hydroxyurea has shown effectiveness against proliferative features and treatment with a hypomethylating agent can benefit patients with dysplastic features, these therapy options do not foster long-term remission or prevent disease progression to acute leukemia.

Currently, allo-SCT is the only potentially curative treatment across MDS/MPN types, but significant morbidity and mortality limit more widespread use of allo-SCT. It is typically not recommended for patients who are of an older age or who have comorbidities; but when possible, allo-SCT should be a go-to approach, the authors wrote.

The only treatment with curative potential remains allo-SCT, which should be provided to all patients with prognostically unfavorable, rapidly evolving, or symptomatic CMML, or other MDSs/MPNs, who have an available stem cell donor, the authors wrote. Ideally, this should be performed early, before disease progression, because in the latter case, nonrelapse mortality and relapse rate are higher and worse than those in [acute myeloid leukemia] evolved from classical MDS.

The authors highlight a selection of studies aiming to show the value of allo-SCT for patients who have MPNs and MDSs. A report from Mayo Clinic including 406 patients, 70 of whom underwent allo-SCT, found that median leukemia-free survival was significantly better in patients who underwent allo-SCT vs the nontransplanted cohort (40 vs 20 months). OS was also superior in the transplanted group (40 vs 21 months).

In another multicenter analysis including 261 patients, 119 of whom underwent allo-SCT, patients who underwent transplant had superior median OS (4.3 vs 2.3 years) compared with those who did not after a median follow-up of 6 years.

Several factors have been shown to have an impact on allo-SCT prognosis in patients who have CMML. Early transplantation is an important aspect of success in MPNs and MDSs, and patients Hematopoietic Cell Transplantation-Specific Comorbidity Index scores have also shown prognostic value in several studies. The percentage of bone marrow blasts, pre-transplant cytogenetics, pre-transplant hematocrit, and age have also been shown to impact survival.

The most challenging decision for the treating physician concerns patients between 60 and 70 years and few fit patients older than 70 years, the authors wrote. For this age range, the physician needs to discriminate higher-risk features that have been well characterized and described. A disease mutational profile can greatly help in any case but particularly for patients of the seventh decade of their life.

Helping patients achieve the best possible disease status ahead of allo-SCT is the most crucial aspect of successful implementation, the authors noted. The treatment armamentarium includes traditional therapies such as hypomethylating agents and novel options, but choosing the best strategy for each individual can be challenging.

Establishing the most appropriate drug combinations in each individual patient is a long way, which could be delineated through the use of these combinations either as a bridging treatment before transplantation or by incorporating appropriate drugs in the preparatory conditioning regimens, the authors wrote. All of these potential new directions could only be substantiated through prospective multicenter randomized trials.

Reference

Symeonidis A, Chondropoulos S, Verigou E, Lazaris V, Kourakli A, Tsirigotis P. Allogeneic hematopoietic stem cell transplantation for mixed or overlap myelodysplastic/myeloproliferative disorders.Front Oncol. Published online August 5, 2022. doi:10.3389/fonc.2022.884723

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Early Timing, Optimal Conditioning Maximize Outcomes of Allo-SCT in MDSs and MPNs - AJMC.com Managed Markets Network

image:Karla Santos-de-Frutos and Nabil Djouder in the lab. view more

Credit: Antonio Tabernero. CNIO

The intestine is very susceptible and is affected by the harsh conditions caused by DNA-altering agents, such as radiation and chemotherapy, during cancer treatment. For example, many patients with tumours in the gastrointestinal cavity receive radiotherapy, a treatment that often also damages the healthy intestine and affects its regenerative capacity. It is therefore very important to understand how intestinal epithelial regeneration occurs. The cellular and molecular mechanisms involved in this key process are not yet fully understood.

Researchers at the Spanish National Cancer Research Centre (CNIO) have now discovered one of the cellular and molecular mechanisms essential for the regeneration of the intestinal epithelium. This finding lays the foundations for stimulating this process if it fails, and for protecting it against damage caused by radiotherapy and chemotherapy.

According to the study, what prompts intestinal stem cells to regenerate the mucosa depends on the communication between different cell types in the epithelial tissue. The researchers have also found a way to intervene in this communication, and thereby, boost intestinal regeneration.

The paper is published this week in Journal of Experimental Medicine. The research is led by the head of the CNIO's Growth Factors, Nutrients and Cancer Group, Nabil Djouder, and Almudena Chaves-Prez and Karla Santos-de-Frutos are first authors.

The group has spent years researching how to improve the regeneration of various organsparticularly the liver and intestinal mucosaand thus mitigate the effects of radiotherapy. Their findings during this period have been published in high-impact journals.

'Fascinating' four-way cellular communication

"Regeneration of the intestinal epithelium is very important in the proper functioning of the intestine," explains Djouder. "Until now, we knew that it was driven by powerful mitogenic factorsproteinsthat stimulate the proliferation of intestinal stem cells, but we didn't know how these factors were regulated."

This new study suggests thatunexpectedly for the researchers it is the progenitor cells involved in regenerating the epithelial mucosa that modulate the production of mitogenic factors. The process is as follows: when severe damage occurs, injury to the progenitor cells leads to tissue inflammation; this in turn slows down the production of mitogenic factors and thus the proliferation of stem cells and the subsequent regeneration of the mucous membrane.

"For us, this communication between at least four different cell types is new: progenitor cells, which differentiate to form the epithelial mucosa; cells that secrete mitogenic factors; inflammatory cells; and intestinal stem cells themselves," says Djouder. "This communication must be very well controlled, so that the tissue responds appropriately to aggressions."

"That progenitor cells communicate with inflammatory cells and coordinate the proliferation rate of intestinal stem cells is fascinating," he adds.

Djouder places particular emphasis on the new role that progenitor cells have been found to play: "Our study suggests that progenitor cells are not mere bystanders in the process of epithelial regeneration, but play an active and important role in the decisions that intestinal stem cells make in regeneration. Progenitor cells tell intestinal stem cells when and how to divide, and thus control their self-regeneration."

Reducing the side effects of radiotherapy

"This study has allowed us to better understand cell cooperation in order to find new ways to reduce adverse effects in traditional cancer treatments," say Chaves-Prez and Santos-de-Frutos, lead authors of the paper.

The group has also confirmed findings observed in previous work, namely that c-MYC oncogene plays a key role in regeneration. Due to radiation damage and the increase of c-MYC in progenitor cells, inflammation in the intestine increases and mitogenic protein levels are reduced; however, by removing or inhibiting c-MYC, the process is reversed: inflammation is reduced, mitogenic factors increase and intestinal regeneration during severe damage improves.

"Our data show an unexpected role for progenitor cells in the control of inflammatory signalling and mitogenic factor production, essential for maintaining intestinal stem cell proliferation and tissue regeneration," the authors write.

The finding, they say, breaks new ground in research into how to counteract the side effects of radiotherapy in patients with gastrointestinal cancer.

The work has been funded by the Ministry of Science and Innovation, the Carlos III Health Institute, the European Regional Development Fund, the Community of Madrid and the Spanish Association Against Cancer.

Article reference

Transit-amplifying cells control R-spondins in the mouse crypt to modulate intestinal stem 2 cell proliferation. Almudena Chaves-Prez1, Karla Santos-de-Frutos et al. (Journal of Experimental Medicine).

DOI: 10.1084/jem.20212405

Journal of Experimental Medicine

Experimental study

Transit-amplifying cells control R-spondins in the mouse crypt to modulate intestinal stem 2 cell proliferation

13-Sep-2022

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Discovered key mechanisms to improve intestinal regeneration and alleviate the side effects of radiotherapy - EurekAlert

According to the latest report by IMARC Group Nerve Repair and Regeneration Market: Global Industry Trends, Share, Size, Growth, Opportunity and Forecast 2021-2026, The globalnerve repair and regeneration marketexhibited strong growth during 2015-2020. Looking forward, IMARC Group expects the market to grow at a CAGR of around 12% during 2021-2026.

Nerve repair and regeneration (NRaR) is performed to support the replacement of injured nervous tissue caused by trauma or neurodegenerative diseases. It promotes the regrowth of new neurons, myelin, axon, synapses, and glial cells to restore normal nerve functionalities. NRaR employs biomaterials, along with neurostimulation and neuromodulation devices, for conducting nerve grafting, direct Neurotherapy, stem cell therapy, transcranial magnetic, and sacral nerve stimulation. As a result, they are extensively applied in cell relocation studies, material sciences, and nanotechnology and bioengineering fields.

Market Trends:

The increasing prevalence of neurological disorders and rising incidents of nervous injuries, especially in the geriatric population, represent the key factors contributing to the global NRaR market growth. In line with this, extensive research and development (R&D) activities in the field of neurology to introduce advanced NRaR products are further catalyzing market growth. Moreover, rising healthcare expenditure and the widespread adoption of effective management and treatment strategies, such as endogenous and exogenous stem cell transplantation, are positively influencing the market growth.

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We are regularly tracking the direct effect of COVID-19 on the market, along with the indirect influence of associated industries. These observations will be integrated into the report.

Competitive Landscape:

The competitive landscape of the market has been studied in the report with the detailed profiles of the key players operating in the market.

Some of these key players include:

Explore full report with table of contents:https://www.imarcgroup.com/nerve-repair-regeneration-market

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Intensive first-line treatment with high-dose chemotherapy and autologous stem cell transplant was not associated with higher rates of late effects compared with outcomes from less intensive therapies in patients with mantle cell lymphoma.

Intensive first-line treatment with high-dose chemotherapy and autologous stem cell transplant (ASCT) was not associated with higher rates of late effects compared with outcomes from less intensive therapies in patients with mantle cell lymphoma (MCL), according to findings from a population-based study. The results also showed that patients with MCL had a higher rate of outpatient visits, hospitalizations, and bed days vs healthy comparators.

When compared with matched comparators from the general population, patients with MCL had a rate of outpatient visits during follow-up that was 2 times higher (incidence rate ratio [IRR], 2.0; 95% CI, 1.8-2.2). Furthermore, rates of inpatient visits for those with MCL were 7 times higher (incidence rate ratio for inpatient visits, 7.2 [95% CI, 6.3-8.3] and incidence rate ratio for bed days was 8 times higher, 8.3 [95% CI, 6.8-10.1]) 12 months after MCL diagnosis.

Studies of late effects by different MCL therapies are of interest as new treatments are introduced and the role of [high-dose chemotherapy plus] ASCT is questioned, and may provide a basis for novel treatment strategies and improvements in supportive care and follow-up, lead study author, Sara Ekberg, of the Uppsala University and Uppsala Akademiska Hospital, and colleagues, wrote.

The current standard of care for younger patients with MCL is rituximab (Rituxan) with dose-intensified cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP) and high-dose cytarabine, followed by high-dose chemotherapy and ASCT, also known as the Nordic MCL2 protocol. However, the benefit of chemoimmunotherapy with consolidating high-dose chemotherapy plus ASCT in this era of novel targeted agents is still to be determined.

Additionally, population-based studies that include patients treated with high-dose chemotherapy and ASCT are necessary to determine the magnitude and panorama of the late effects of MCL outside the context of clinical trials.

This population-based study aimed to describe the late effects experienced by patients with MCL treated with or without high-dose chemotherapy and ASCT.

This study cohort included all patients with MCL recorded in the Swedish Lymphoma Register between the ages of 18 and 69 years who received a diagnosis between 2000 and 2014 (n = 620). A total of 247 patients were treated with high-dose chemotherapy plus ASCT and 373 of whom were not.

Patients in the study cohort were matched 1:10 with healthy comparators (n = 6200) from the general population based on birth year, sex, and lymphoma-free status at the date of the patients MCL diagnosis. The median age was 65 years (range, 22-69) for nonHD-ASCT patients and 58 years (range, 32-69) for HD-ASCT patients. The median age of the comparators was 63 years (range, 22-70).

Patients with MCL were classified as HD-ASCT patients if they had received high-dose chemotherapy and ASCT within 12 months of diagnosis. Patients were classified as nonHD-ASCT if they had not received this therapy within 12 months of diagnosis.

Regarding comorbidity, as measured per the Charlson Comorbidity Index, in the nonHD-ASCT group, 57.1% (n = 213), 13.4% (n = 50), and 29.5% (n = 110) had a comorbidity index of 0, 1, or 2 or greater, respectively. In the HD-ASCT group, 76.9% (n = 190), 8.9% (n = 22), and 14.2% (n = 35) had a comorbidity index of 0, 1, or 2 or greater, respectively. Of the comparators, 75.3 (n = 4669), 11.5% (n = 715), and 13.2% (n = 816) had a comorbidity index of 0, 1, or 2 or greater, respectively.

In general, the HD-ASCT patients received R-maxi-CHOP alternated with rituximab plus cytarabine, as well as consolidative high-dose chemotherapy with carmustine, etoposide, cytarabine, and melphalan (BEAM) or carmustine, etoposide, cytarabine, and cyclophosphamide (BEAC) prior to transplant. The nonHD-ASCT patients mostly received R-CHOP plus cytarabine, R-CHOP, rituximab plus bendamustine, or chlorambucil alone. A total of 14 patients received rituximab maintenance.

Among the HD-ASCT patients, 47% underwent transplant within 6 months of diagnosis, and 83% underwent transplant within 12 months of diagnosis, leading to the selected cutoff date of 12 months for the classification of the HD-ASCT group.

Investigators followed patients and comparators through the Swedish Patient Register and Cause-of-Death-Register from 12 months after diagnosis or matching until death or December 31st, 2017. Patients and comparators who died before the start of follow-up were excluded from the landmark analysis.

HD-ASCT patients had a slightly higher rate of outpatient visits during the first 5 years after diagnosis compared with nonHD-ASCT patients (IRR, 1.3; 95% CI, 1.0-1.6). Additionally, HD-ASCT patients had lower rates of inpatient visits 5 to 10 years after diagnosis compared with nonHD-ASCT patients, with an IRR of 0.6 (95% CI, 0.4-0.9). The total rates of bed days were similar between the 2 groups, at 1.1 (95% CI, 0.7-1.6) and 1.0 in the HD-ASCT and nonHD-ASCT groups, respectively.

After 10 years of follow-up, the rates of outpatient visits and hospitalizations were similar between HD-ASCT and nonHD-ASCT patients. Regarding outpatient visits, the IRR were 0.7 (95% CI, 0.5-1.1) and 1.0 for the HD-ASCT and nonHD-ASCT groups, respectively.

The short-term complications, defined as those that occurred within 60 days after transplant in HD-ASCT patients, included blood and blood-forming organ diseases (27.5%), infectious diseases (26.3%), circulatory system diseases (14.2%), and digestive system diseases (9.3%). Other common complications included respiratory system diseases (6.1%), skin and subcutaneous tissue diseases (5.7%), endocrine diseases (4.9%), and genitourinary system issues (4.0%). Musculoskeletal system diseases and mental complications were rare, occurring in 2.4% and 0.8% of patients, respectively. The median duration of hospitalization after high-dose chemotherapy plus ASCT was 22 days; 2 patients (0.8%) in this group died within 60 days after transplant.

The long-term complications investigated among all patients and comparators included the first specialist outpatient visit, hospitalization, or death at least 12 months after diagnosis within any of the 15 mutually exclusive disease groups defined by the investigators. Additionally, investigators quantified all specialist outpatient visits, bed days, and hospitalizations starting from 1 year after diagnosis to illustrate the total health care burden.

When compared with the matched comparators, the patients with MCL had higher relative risks and health care burdens for blood and blood-forming organ diseases (comparators, HR, 1.00 vs nonHD-ASCT, HR, 9.84 [95% CI, 6.91-14.00]; HD-ASCT, HR, 5.80 [95% CI, 3.42-9.84]), respiratory system diseases (comparators, HR, 1.00; nonHD-ASCT, HR, 4.38 [95% CI, 3.53-5.42]; HD-ASCT, HR, 5.26 [95% CI, 4.08-6.77]), and infectious diseases (comparators, HR, 1.00; nonHD-ASCT, HR, 4.66 [95% CI, 3.62-5.99]; HD-ASCT, HR, 5.62 [95% CI, 4.20-7.52]). These rates were seen irrespective of high-dose chemotherapy and ASCT treatment status. These patterns were also observed in the sensitivity analysis at 9, 18, and 24 months after diagnosis.

The most common respiratory disorders included influenza, upper respiratory infections, and pneumonia. The most common infectious diseases were bacterial infections, although HD-ASCT patients had a higher incidence of viral infections than nonHD-ASCT patients. The most common blood and blood-forming organ diseases were anemia, immunodeficiency, idiopathic thrombocyte platelet deficiency, and other diseases.

The rates of secondary malignancies, including melanoma, neoplasms of the skin, prostate cancer, and malignant neoplasm in the urinary tract, were comparable between HD-ASCT and nonHD-ASCT patients.

Deaths from causes other than MCL occuring at least 12 months after diagnosis were rare in both MCL patient groups. The 5-year cumulative probabilities of MCL-specific death were 23% (95% CI, 18%-30%) and 32% (95% CI, 26%-38%) in HD-ASCT and nonHD-ASCT patients, respectively. A standardized analysis showed no evidence of difference in cumulative probabilities of MCL-specific death between the 2 groups when subgroup differences were eliminated.

Avoiding efficient MCL treatment because it is more demanding and possibly causes late effects may seem reasonable in the short term, but our results indicate that the vast majority of long-term healthcare needs in patients up to 70 years is related to the lymphoma. This calls for continued efforts to improve treatment efficacy in MCL, the study authors concluded.

Ekberg S, Smedby KE, Albertsson-Lindblad A, et al. Late effects in mantle cell lymphoma patients treated with or without autologous stem cell transplantation. Blood Adv. Published online August 16, 2022. doi:10.1182/bloodadvances.2022007241

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Late Effects Arise Irrespective of High-Dose Chemotherapy and ASCT Status in MCL - OncLive