Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol

Rajendra, Akhil; Jain, Hasmukh; Bonda, V. N. Avinash; Nayak, Lingaraj; Tembhare, Prashant; Shetty, Dhanlaxmi; Thorat, Jayashree; Jain, Hemani; Subramanian, Papagudi Ganesan; Patkar, Nikhil; Chatterjee, Gaurav; Khattry, Navin; Gokarn, Anant; Punatar, Sachin; Mokal, Smruti; Bagal, Bhausaheb; Sengar, Manju

doi:10.1182/bloodadvances.2020003526

Cited by 21 publications

(25 citation statements)

References 81 publications

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“…Although these are much higher than other studies using rituximab in ALL, a very similar trend has been seen in our patients undergoing induction therapy for acute leukemia and adolescent and young adult ALL. 18,21,22 Higher infection rates compared with the reported literature did not increase induction mortality than the reported literature (3%-7%). 11,12,25 We observed no grade 3 or higher neuropathy despite combining 2 potentially neurotoxic drugs.…”

Section: Discussionmentioning

confidence: 51%

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Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia

Jain¹,

Sengar²,

Goli³

et al. 2021

Blood Advances

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The expression of CD20 in precursor B-cell ALL is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD-20 positive ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD) negative status post-induction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD negative complete responses in patients with high-risk ALL. Given bortezomib's activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20-positive-precursor B-cell ALL. We conducted a phase II study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (>14 years of age) with CD20-positive, Philadelphia (Ph)-negative precursor B- ALL, with bone marrow MRD negativity at the end of induction (EOI) as the primary endpoint. From December 2017 through August 2019, a total of 35 patients were enrolled. EOI-MRD-negative status was achieved in 70.99% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, the event-free survival and overall survival were 78.8% [95% CI - 66%- 94%] and 78.7% [95% CI - 65.8%- 94%], respectively. There was no significant increase in toxicity with bortezomib and rituximab compared to the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen is active and well-tolerated in de-novo CD20-positive Ph-negative precursor B-ALL. This trial is registered with the Clinical Trials Registry-India, CTRI/2017/04/008393.

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Section: Discussionmentioning

confidence: 51%

“…All patients received the modified BFM-90 protocol, 21 with no highrisk blocks of chemotherapy. Rituximab was given as an intravenous infusion at a dose of 375 mg/m 2 of body surface area, once weekly for 5 doses during induction (on days 1, 8, 15, 22, and 28).…”

Section: Treatment and Proceduresmentioning

confidence: 99%

Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia

Jain¹,

Sengar²,

Goli³

et al. 2021

Blood Advances

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“…Beyond discussions about the definition of the AYA age group, we were not able to identify any papers specifically dedicated to allogeneic HSCT in an AYA ALL population. Published ALL studies reported overall results of ALL therapy in this population but did not necessarily disclose how an AYA group was defined, state whether there were any adjustments in the HSCT indications for this group compared with indications for children or adults, or address HSCT results specifically in AYAs ( 15 , 20 ). In paediatric studies, AYAs are often limited to 18–21-year-old patients and results are not provided for older AYAs ( 20 ).…”

Section: Indication For Hsctmentioning

confidence: 99%

“…Published ALL studies reported overall results of ALL therapy in this population but did not necessarily disclose how an AYA group was defined, state whether there were any adjustments in the HSCT indications for this group compared with indications for children or adults, or address HSCT results specifically in AYAs ( 15 , 20 ). In paediatric studies, AYAs are often limited to 18–21-year-old patients and results are not provided for older AYAs ( 20 ). In adult studies, AYAs are usually included in the overall cohort along with 40–60 years old patients; this probably worsen their outcome vs. if the older patients were studied separately.…”

Section: Indication For Hsctmentioning

confidence: 99%

Haematopoietic Stem Cell Transplantation in Adolescents and Young Adults With Acute Lymphoblastic Leukaemia: Special Considerations and Challenges

et al. 2022

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Adolescents and young adults (AYAs) represent a challenging group of acute lymphoblastic leukaemia (ALL) patients with specific needs. While there is growing evidence from comparative studies that this age group profits from intensified paediatric-based chemotherapy, the impact and optimal implementation of haematopoietic stem cell transplantation (HSCT) in the overall treatment strategy is less clear. Over recent years, improved survival rates after myeloablative allogeneic HSCT for ALL have been reported similarly for AYAs and children despite differences in transplantation practise. Still, AYAs appear to have inferior outcomes and an increased risk of treatment-related morbidity and mortality in comparison with children. To further improve HSCT outcomes and reduce toxicities in AYAs, accurate stratification and evaluation of additional or alternative targeted treatment options are crucial, based on specific molecular and immunological characterisation of ALL and minimal residual disease (MRD) assessment during therapy. Age-specific factors such as increased acute toxicities and poorer adherence to treatment as well as late sequelae might influence treatment decisions. In addition, educational, social, work, emotional, and sexual aspects during this very crucial period of life need to be considered. In this review, we summarise the key findings of recent studies on treatment approach and outcomes in this vulnerable patient group after HSCT, turning our attention to the different approaches applied in paediatric and adult centres. We focus on the specific needs of AYAs with ALL regarding social aspects and supportive care to handle complications as well as fertility issues. Finally, we comment on potential areas of future research and concisely debate the capacity of currently available immunotherapies to reduce toxicity and further improve survival in this challenging patient group.

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“…Most referral institutions in the country are now transitioning towards paediatric‐inspired protocols for the treatment of ALL in the adolescent and young adult group of patients. A recent systematic review and large retrospective studies indicate this transition in treatments 27,37 . This has also been facilitated by an increasing crosstalk and collaboration occurring between adult and paediatric haemato‐oncology physicians within and outside their respective institutions.…”

Section: The Perspective From India (Vs Radhakrishnan and M Chandy)mentioning

confidence: 99%

Precursor B‐cell acute lymphoblastic leukaemia—a global view

et al. 2021

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As haematologists, we always seek to follow standardised guidelines for practice and apply the best treatment within our means for our patients with blood diseases. However, treatment can never follow an exact recipe. Opinions differ as to the best approach; sometimes more than one treatment approach results in identical outcomes, or treatments differ only by the manner in which they fail. Furthermore, the haematologist is faced with constraints relating to the local economic environment. Patients too are not the same the world over. Early presentation is commoner in the developed world, as is the patient's understanding of the disease process. This in turn has an impact on the way patients are managed, the rigorousness of patient adhesion to the treatment schedule and the outcome. Here we take a look at the precursor B-cell acute lymphoblastic leukaemia in an adolescent in a range of different settings from low-to high income countries with widely differing challenges for diagnosis, therpy and follow-up. For these reasons, given the same starting conditions, patients will be treated differently according to the institute and the country they are in. Experts from around the world have been tasked to describe their management plan and rationale for a specific disease presentation. Here they explore the management of precursor B-cell acute lymphoblastic leukaemia (pre-B ALL) in five different institutions worldwide with a focus on those with more or less strained economies. We end with a conclusion from an expert in the field comparing and contrasting these different management styles and considering their merits and limitations.

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Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol

Cited by 21 publications

References 81 publications

Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia

Bortezomib and rituximab in de novo adolescent/adult CD20-positive, Ph-negative pre-B-cell acute lymphoblastic leukemia

Haematopoietic Stem Cell Transplantation in Adolescents and Young Adults With Acute Lymphoblastic Leukaemia: Special Considerations and Challenges

Precursor B‐cell acute lymphoblastic leukaemia—a global view

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