**6. Comorbidity**

Of older ALL patients, 60–70% suffer from comorbidities, but most studies did not refer to validated scoring systems. The German multicentre study group for adult ALL (GMALL) identified comorbidities according to the Charlson score in 84% of the patients older than 55 years, with diabetes (46%), vascular disease (18%), heart failure (15%), and chronic lung disease (12%) being the most frequent. In addition, renal insufficiency, anemia, osteoporosis, dementia, and depression are probably the most relevant comorbidities for potential adjustment of treatment. About 8–16% had a history of prior malignant disease. I recommend a systematic evaluation and documentation of comorbidities based on a checklist or a score, since this is essential for planning an optimal treatment strategy [4, 5, 18, 23].

Comorbidities in elderly patients with ALL require a specialized and detailed approach. The German multicentre study group for adult ALL (GMALL) recommends the use of the Charlson scale for the determination of risk due to comorbidities; this assessment must be done in an integral manner, together with the physics, biochemistry, and cytomolecular evaluation of the disease [4]. Multiple systemic

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*Overview and Current News in Acute Lymphoblastic Leukemia*

diseases can afflict elderly patients with ALL: diabetes, hypertension, heart failure, and renal failure are some of the most frequently reported in the various studies conducted. Age-specific conditions such as dementia or osteoporosis that can negatively impact the patient's performance before and after treatment should not be left aside. It is also important to evaluate, monitor and, if necessary, treat alterations in the emotional state of the elderly patient, since depression and anxiety are not

Now, we have a better understanding of the factors that determine survival, but these will require reexamination as we introduce novel therapies. Cytogenetic findings such as Philadelphia chromosome positivity, t (4; 11), complex cytogenetic abnormalities (more than five chromosomal changes), and low hypodiploidy/near triploidy result in inferior survival. Some of these changes are more common in older adults. Other conventional factors such as increasing age, high white blood cell count, and B-cell disease (rather than T-cell disease) still hold true and predict higher failure rates with standard chemotherapy. However, many of these factors are also associated with a higher relapse rate after allografting, and it is not necessarily the case that bone marrow transplantation (BMT) is the solution for patients with adverse prognostic features. Combining these factors may allow individualization of therapy, a prospect not previously possible in this rare condition. As well as undertreating patients with ALL with chemotherapy that is likely to fail, prognostic factors should be used to avoid over treating better prognosis patients with allogeneic transplants that have a high upfront risk and may result in chronic graft-versus host disease (GVHD), infertility, and secondary malignancy. Chemotherapy and transplant have complementary roles in ALL management, and a pragmatic approach is required to deliver the best outcomes. The role of BMT is likely to increase, especially with the promising results of reduced-intensity allografting, but conversely, the use of BMT should be reduced if

advances in nontransplant therapy improve cure rates [11, 17, 20, 23].

experimental treatments, if they were available [18–20, 24].

Increasing age itself is one of the most relevant prognostic factors for outcome of ALL from childhood to old age. Since older patients show opposite problems, namely higher mortality and relapse rates, prognostic factors for both have to be analyzed. Prognostic factors for relapse risk in younger ALL patients are probably also valid in older patients, such as early and mature T-ALL, pro-B ALL, elevated white blood cell count, and Ph+ ALL; however, their predictive value is somewhat diluted by mortality risks. Evaluation of minimal residual disease (MRD) has demonstrated that persistence of MRD is associated with a relapse rate above 90% in younger patients despite continued intensive chemotherapy. Few data on the prognostic impact of MRD are available in older patients. In one study, only 11% of the older patients with molecular failure after first consolidation remained in complete response (CR) compared with 68% of those with molecular remission. In older patients with less intensive therapy, a higher rate of MRD persistence and an even poorer outcome can be expected. Therefore, prospective evaluation of MRD in older patients is essential to identify those who could benefit from alternative

Some poor prognosis factor applicable to young patients can also be in elderly patients, which tells us of the profound impact they have on the biology of the disease: the T lineage and the positive Phi chromosome are a pair of these. The persistence of positive minimal residual disease is directly related to an increased frequency of relapse after remission; it is estimated that young patients with positive MRD will relapse up to 90% despite receiving intensive CT. We do not have

*DOI: http://dx.doi.org/10.5772/intechopen.86662*

infrequent conditions in this group [5, 18, 22].

**7. Prognostic factors in older ALL patients**

*Geriatric Medicine and Gerontology*

**5. Clinical status**

**6. Comorbidity**

intensiveness of therapy administered [8, 20].

karyotype changes that occur in ALL can be roughly subdivided in those associated, respectively, with a relatively good, intermediate, and poor prognosis. However, it must be kept in mind that the incidence of certain aberrations is very low, and that for some of them, the prognostic impact can be strongly affected by the type and

Features associated with large tumor mass or rapid progression, such as high white blood cell count, mediastinal tumors, or other organ involvement, appear to be less common in older patients. Even "smoldering" ALL is observed in some cases. Most studies report a lower proportion of males among older ALL patients. Secondary ALL after myelodysplastic syndromes or other malignant disease may become increasingly important, particularly in older patients; so far, very limited data are available. Performance status often deteriorates in older patients with onset of disease. In two studies, 30–43% of patients older than age 60 years vs. 18–22% of younger patients had a performance status of 2 or more. Therefore, it is important not only to consider the current general condition in newly admitted older ALL patients but also to discern

The determination of the clinical status at the moment of making the diagnosis provides us with information about the global state of the patient, so that we can make better decisions. This varies in comparison with the younger groups in questions such as the low initial presentation of large tumor mass, identified by the elevated white blood cells count in the peripheral blood, the rare extranodal affection and even in some cases being observed, apparently "benign" clinical presentation with low tumor burden. A smaller proportion of male patients in this group have also been observed as compared with younger groups. Secondary leukemia, which we define as that which occurs after a premalignant pathology, most frequently myelodysplastic syndrome, or after treatment of nonhematological neoplasms, is a condition that has been observed more and more frequently in recent years. However, there is little data to help us determine its nature. It is important to assess these patients comprehensively in order to determine their physical and

their status before the onset of leukemia-associated symptoms [17, 21].

health status prior to the onset of symptoms related to leukemia [17, 21].

Of older ALL patients, 60–70% suffer from comorbidities, but most studies did not refer to validated scoring systems. The German multicentre study group for adult ALL (GMALL) identified comorbidities according to the Charlson score in 84% of the patients older than 55 years, with diabetes (46%), vascular disease (18%), heart failure (15%), and chronic lung disease (12%) being the most frequent. In addition, renal insufficiency, anemia, osteoporosis, dementia, and depression are probably the most relevant comorbidities for potential adjustment of treatment. About 8–16% had a history of prior malignant disease. I recommend a systematic evaluation and documentation of comorbidities based on a checklist or a score, since this is essential for planning an optimal treatment strategy [4, 5, 18, 23]. Comorbidities in elderly patients with ALL require a specialized and detailed approach. The German multicentre study group for adult ALL (GMALL) recommends the use of the Charlson scale for the determination of risk due to comorbidities; this assessment must be done in an integral manner, together with the physics, biochemistry, and cytomolecular evaluation of the disease [4]. Multiple systemic

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diseases can afflict elderly patients with ALL: diabetes, hypertension, heart failure, and renal failure are some of the most frequently reported in the various studies conducted. Age-specific conditions such as dementia or osteoporosis that can negatively impact the patient's performance before and after treatment should not be left aside. It is also important to evaluate, monitor and, if necessary, treat alterations in the emotional state of the elderly patient, since depression and anxiety are not infrequent conditions in this group [5, 18, 22].
