Question: Dr. Chiragbhai, thank you for explaining in last part about some of the special subtypes of Non Hodgkin’s Lymphoma, namely MALT, Splenic marginal zone, Waldenstrom’s, Hairy cell, mycosis fungoides, LGL. These are very interesting types with highly variable treatment, clinical course, including treatment without chemotherapy in many cases.
Ans: Today we will discuss some other important aspects of lymphoma treatment. Supportive care in intermediate and aggressive lymphomas is similar to acute leukemias in many ways. This is conceptually different from Solid Tumors like breast, lung cancers etc. It is important to realize that intermediate in some cases and aggressive lymphomas in most cases are rapidly growing, and hence need rapid treatment, unlike solid tumors. Also one has to be careful about risk of TLS-tumor lysis syndrome, spinal cord compression, infiltration of visceral organs, bulky disease causing organ compression, and risk of CNS spread. Therapy and disease related immune suppression with secondary infections is also a concern.
Que: I can understand complications of a rapidly progressive disease, but what is TLS?
Ans: TLS, as the name suggests, is the result of Tumor Lysis. Lysis of any tumor cells, if rapid enough, can lead to TLS. This is most common in acute leukemias, and lymphomas, but also seen occasionally in low grade lymphomas, and even solid tumors. Rapid cell lysis, either spontaneous, or due to treatment, releases large amounts DNA which is metabolized to uric acid. Large amount of uric acid crystals block and injure kidney tubules, leading to acute renal failure. Cell cytoplasm is also rich in phosphorous and potassium. Hence, release of large amounts can cause hyperkalemia, and high phosphorus which in turn causes hypocalcemia. In presence of reduced renal function, this combination is particularly dangerous, and leads to sudden cardiac arrest and death.
Que: That sounds scary. How common is this, and how can we prevent it?
Ans: Variable degree of TLS is fairly common. Severe TLS is fortunately not common now, as oncologists are now aware of this complication, and institute preventive measures quickly after diagnosis of lymphoma or leukemia. But it is important for our non oncology readers to recognize this, as it is a fatal complication, and they can also advise preventive steps when leukemia or lymphoma is suspected.
Most important Risk Factors are rapidly progressive disease, bulky disease, high LDH, already high uric acid or creatinine. Most important Preventive Steps are aggressive hydration, and allopurinol even if uric acid is normal. Alkalinization of urine was once thought to be important, but now hydration is considered the more important aspect. One very important step now taken by oncologists is to start treatment gently, i.e. use of only steroids or low dose chemotherapy in first week of therapy. This allows initial slow breakdown of tumor cells, and allows allopurinol to reduce uric acid to lowest possible.
One very important new advance is drug called RASBURICASE. It is now widely available, somewhat expensive however, but provides excellent prevention in high risk cases, and treatment in established cases of TLS. Only one vial given at start of treatment, often reduces uric acid level from high to less than 1. Also, it provides this reduction very rapidly, in generally 4-8 hours. Preventive dialysis to bring down uric acid, before chemotherapy, can be done if rasburicase is contraindicated, such as in patients with G-6PD deficiency.
Que: Thank you. What about immune suppression you mentioned earlier? I thought all chemotherapy, even for solid tumors, would reduce blood counts.
Ans: Yes, but level of immune suppression with aggressive lymphomas and leukemias is much higher. Here, the cells which provide immunity are themselves affected. On top of that, treatment frequently involves large doses of steroids and more aggressive chemotherapy compared to breast cancer or other solid tumors. Hence risk of bacterial and fungal infections is significantly higher, and needs specific care, monitoring, and preventive medicines.
Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. firstname.lastname@example.org Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com