Cannabis Extract Therapy for Lymphoblastic Leukemia

Serious lymphoblastic leukemia is a tumor of the white blood cells and is typically well cured with combination chemo, with a remission time after five years of 94 percent in children and 30-40 percent in adults. To determine how aggressive the tumor is, further chromosome testing is required to decide whether involves neutrophils and the tumor is myeloblastic, basophils or eosinophils, or lymphoblastic involving T or B lymphocytes. This case study is on a 14-year-old case diagnosed with a very aggressive form of Acute lymphoblastic leukemia (positive for the Philadelphia chromosome mutation). A standard bone marrow transplant, radiation therapy were revoked, and aggressive chemotherapy, with therapy being deemed a defeat after 34 months. Without any other solutions provided by conventional approaches aside from palliation, the family administered cannabinoid extracts (CBD, CBDV, CBG)  orally to the patient. The resin of the cannabis plant is used as an effective treatment for ALL with a positive Philadelphia chromosome mutation and indications of dose-dependent disease control. The clinical note in this research revealed a fast dose-dependent correlation.

Presentation of the Case:

A 14-year-old female, P.K., presented with symptoms of weakness, shortness of breath and bruising when she was taken to the Hospital for Sick Children, Toronto, Canada, on the 10th March 2006. The patient was diagnosed with disease ALL (acute lymphoblastic leukemia), with more than 300,000 blast cells present. Acute chemo treatment followed by a regular chemotherapy regimen went on for 6 months after the examination. Upon further tests, she was affirmed to be positive for the Philadelphia chromosome mutation. A mutation in the Philadelphia chromosome is a extremely more chronic form of acute lymphoblastic leukemia. When standard therapy options were failing, a bone marrow transplant was pursued. She successfully received the transplant in August 2006 and was capable to be released from isolation 45 days later. She was observed posttransplant by following the presence of blast cells, noted 6 months after treatment. Then, in February 2007, attacker chemotherapy procedures (AALL0031) were managed along with imatinib mesylate (Gleevac), a tyrosine kinase inhibitor, 500 mg orally twice a day. In November 2007, 9 months after the transplant, the presence of premature blast cells was observed and it was determined that another bone marrow transplant would not be effective. In February 2008, in an effort to sustain the patient, another tyrosine kinase inhibitor, disatinib (Sprycel), was administered at 78 mg twice a day with no additional rounds of chemotherapy. The patient experienced increased migraine-like headaches in June 2008.

In July 2008, after conducting a CT scan of the head, cerebellitis was recorded. It was considered by the first oncologist that the blast cells could have sneaked the CNS and be already in the brain, although none were seen in the blood. By October 2008, 10 treatments of radiation therapy had been given to the brain.

In February 2009, blood was noted in the patient’s stools and a blood cell count revealed the presence of blast cells. As an outcome, all therapy including the disatinib was discontinued and the patient’s medical team acknowledged failure in curing her tumor. It was charted by the patient’s hematologist/oncologist that the patient ‘suffers from terminal malignant disease. She has been cured to the limits of available treatment… no more active intervention will be offered’. She was placed in palliative home care and told to prepare for her disease to overwhelm her body and from which she would suffer a stroke within the next 2 months.

Cannabinoid extracts (CBD, CBDV, CBG) Treatment:

After this, disease improvement was observed with increasing counts of blast cells. She was receiving platelets and frequent blood transfusions during this period. Through search conducted by the patient’s parents, it was observed, in a particular paper by Guzman published in Nature Reviews Tumor, that cannabinoids (THC and CBD) have been revealed to inhibit he growth of tumor cells in culture and in animal models by modulating key cell-signaling pathways. cannabinoids (THC and CBD) are normally well-tolerated and do not produce the popularized toxic effects of conventional chemotherapies. The family found promise in an organization known as Phoenix Tears, led by Rick Simpson who had treated several tumors with hemp oil (hemp seed oil), an extract from the cannabis (medical marijuana) plant.  Rick worked with the parents to help them prepare the resin of the cannabis plant.

During February, the patient’s blast cell number had increased from 51,490 to 194,000. The first dose of the resin of the cannabis plant also referred to as ‘hemp oil (hemp seed oil)’, was administered orally (1 drop about the size of half a grain of rice) at 6:30 a.m. on the 21st of February 2009 (day 0 in figure. 1). A 2-ounce Cannabis (medical marijuana) indica strain (known as ‘Chronic Strain’) was used to extract 7.5 ml of hemp oil (hemp seed oil) using 1.2 liters of 99 percent -the isopropyl-alcohol solution, which was boiled off in a rice steamer (rice cooker). Immediately after dosing, the patient attempted to vomit; nausea had been observed previously and is common with this condition. To deal with the bitter taste and viscous nature of the hemp oil (hemp seed oil), it was suspended in honey, a known natural digestive aid, and then administered to the patient in daily doses.The goal was to quickly increase the amount and frequency of the dose and to hopefully build up the patient’s tolerance to the resin of the cannabis plant (refer to fig. 1). The patient was observed to have periods of panic early on during the administration of the hemp oil (hemp seed oil), along with increased appetite and fatigue.

The blast cell number reached a peak of 374,000 at the end of February 2009 (day 5), followed by a reduction, which is associated with the increasing dose.The daily dosing is the amount administered per dose; the doses were initially given once per day up to a total of 3 times per day by day 15, and were continued with the same average frequency throughout the treatment period. Reduced use of morphine for pain, a growing in euphoria symptoms, a disoriented memory and an increase in alertness were observed; these are typical with cannabinoid (THC and CBD) use.

After day 15, the original Chronic Strain had been consumed and administration of a new strain (referred to as hemp oil (hemp seed oil) #2) was started. This was obtained by the family from an outside source. It was noted that giving the same dose yielded a reduced response in terms of the side effects of  appetite and euphoria, and the patient suffered more nausea with this hemp oil (hemp seed oil). The blast cells began to increase, demonstrated in figure2

There is a wide amount of variance in cannabinoid (THC and CBD) concentration amongst different strains and even in the same strain with changes in increasing conditions. The quantity of each dose was increased to rival the response of the blast cells that had been decreasing previously (fig. 1). After day 27, there was another peak blast cell count of 66,000 followed by a rapid drop. There were elevated levels of urate present in the blood with corresponding joint pain; it was established that this was caused by tumor lysis syndrome of the blast cells. Allopurinol was administered.

On the 1st April 2009 (day 41), an infected central line with tunnel infection was noted on a blood test and the patient was admitted with a heavy antibiotic regimen of intravenous tazocin, gentamicin and vancomycin. On day 43, a new batch of hemp oil (hemp seed oil) from an Afghan/Thai strain (referred to as hemp oil (hemp seed oil) #3) prepared by the family was administered. A stronger psychosomatic response and increased fatigue were observed, so dosing was adjusted to 0.5 ml, shown in figure 3. Due to hospital rules, dosing was restricted to twice a day.

A new batch of hemp oil (hemp seed oil) was obtained by the family from an outside source and the dosing regimen continued twice a day, shown in figure 4.

After returning home from the hospital on the 11th April (day 51), the patient suffered from intense nausea, an inability to eat and overall weakness. On the 13th April, the patient was readmitted to the SickKids Hospital and was treated for refeeding syndrome. This was the result of ending total parenteral nutrition too fast and making shock to the patient’s body while she was being cured for the infection. The dosing regimen was intermittent until day 59, remaining at 1-2 doses per day of 0.5 ml. As the blast cells began to increase and the patient’s appetite increased, the dosing frequency was again increased to 3 times per day starting on day 62, and the amount administered was increased from day 65.

On day 68, a new batch of medicine was obtained by the family from an outside source (referred to as hemp oil (hemp seed oil) #5), shown in figure 5.

Dosing was maintained 3 times a day at 1.0 ml. On day 78, the patient had stomach pain in the morning and was admitted to the hospital. Upon X-ray, it was seen that gastrointestinal bleeding had happened. The patient was under a DNR order and ultimately passed away due to the bowel perforation. A former history of pancolitis authenticated by CT scan in March 2009 pointed to neutropenic colitis with perforation as the cause of death. Moreover, prior to starting on the hemp oil (hemp seed oil) therapy, the patient had been very ill, severely underweight and had endured numerous sessions of radiation and chemotherapy therapy in the course of 34 months.

As reported by Hematology/Oncology at SickKids:

‘At acceptance, her total WBC was 1.4,  platelet count 8,000, hemoglobin was 82. The patient was profoundly neutropenic… a prior history of pancolitis notarized by CT scan in March 2009 was neutropenic colitis with perforation… her abdomen was distended and certainly had some signs of diffuse peritonitis. The abdomen X-ray was in favor a perforation…she passed away at 10:05 in the present (sic) of the family…’.

Discussion:

Figure 6 is a summary of dose-response to all the batches of hemp oil (hemp seed oil) administered over a total of 78 days.

The outcomes shown here cannot be attached to the phenomenon of ‘spontaneous remission’ because a dose-response curve was reached. Three factors, namely frequency of dosing, amount given (therapeutic dosing) and the potency of the cannabis (medical marijuana) strains, were critical in determining response and disease control. By viewing figure 6, it can be seen that introducing strains that were less potent, dosing at intervals >8 h and suboptimal therapeutic dosing consistently showed increases in the leukemic blast cell count. It could not be determined which cannabinoid (THC and CBD) profiles constituted a ‘potent’ cannabis (medical marijuana) strain because the resin of the cannabis plant was not analyzed. Research is needed to determine the profile and ratios of cannabinoids (THC and CBD) within the strains that exhibit antileukemic properties.

These results cannot be explained by any other therapies, as the child was under palliative care and was solely on cannabinoid (THC and CBD) treatment when the response was documented by the SickKids Hospital.The toxicology record ruled out chemotherapeutic factors and just revealed her to be positive for tetrahydrocannabinol (THC) when the patient had ‘a recent massive drop of WBC from 350,000 to 0.3′ inducing tumor lysis syndrome, as reported by the first oncologist/hematologist at the SickKids Hospital.

This treatment has to be seen as polytherapy, as many cannabinoids (THC and CBD) within the resinous extract( cannabis extract) have antiproliferative, proved targeted,   antiangiogenic and proapoptotic properties. This also needs to be explored further, as there is potential that cannabinoids (THC and CBD) might show selectivity when attacking tumor cells, thereby reducing the widespread cytotoxic effects of conventional chemotherapeutic agents.It should be noted that where our most developed chemotherapeutic agents had failed to manage the blast numbers and had the devastating consequences that ultimately performed in the death of the patient, cannabinoid (THC and CBD) therapy had no toxic side effects and just psychosomatic properties, with an improvement in the patient’s vitality.

The nontoxic side effects associated with cannabis (medical marijuana) may be minimized by slowly titrating the dosing regimen upwards, building up the patient’s tolerance. The possibility of bypassing the psychoactive properties also exists, by administering nonpsychoactive cannabinoids such as cannabidiol (CBD) that have demonstrated antiproliferative properties. Furthermore, future therapies could examine the possibility of upregulating a patient’s endogenous cannabinoids (THC and CBD) to help combat leukemic cells.It goes without telling that much more study and, even more importantly, stage clinical trials want to be implemented to discover the benefits of such treatments. Laboratory analysis is important to figure out the ratios /constituents/profiles of the vast cannabis (medical marijuana) strains that show the most favored characteristics for exerting possible anticancer effects. Despite the nonstandardization of the medicines, the dose was readily titrated according to the biological response of the patient and produced a potentially life-saving response, namely, the drop in the leukemic blast cell count.

There has been an abundance of research exhibiting the cytotoxic effects of cannabinoids (THC and CBD) on leukemic cell lines in the form of in vitro and in vivo studies [1,2,3,4]. An oncology and hematology journal, Blood, has published numerous papers [2] over the years constructing the biochemical pathway to be elicited by the anticancer properties of cannabinoids (THC and CBD). Our mission, upon analysis of this significant case study which showed a dose-response curve and complete disease control, is to invest effort in and to focus on research and development to advance this therapy. An emphasis needs to be placed on determining the correct cannabinoid (THC and CBD) ratios for different types of tumors, the best method of administration, quality control and standardization of the cannabis (medical marijuana) strains and their growing conditions as well as therapeutic dosing ranges for various tumors contingent on staging and ages. Toxicity profiles favor therapies deriving from cannabis (medical marijuana) because toxicity within the body is greatly reduced and the devastating side effects of chemoradiation (i.e. secondary tumors or death) can be eliminated. It is unfortunate that this therapy does come with some unwanted psychosomatic properties; however, these might be eliminated by target therapies of nonpsychoactive cannabinoids (THC and CBD) such as cannabidiol (CBD) which has garnered much attention as being a potent anti-inflammatory and possible antileukemic and anticancer agent. It is acknowledged that significant research needs to be conducted to reproduce these results and that in vitro studies cannot always be reproduced in clinical trials and the human physiological microenvironment. Nevertheless, this particular clinical case and the various research studies are powerful enough to warrant performing clinical tests to define dose ranges, cannabinoid (THC and CBD) profiles, the methods of administration, and ratios that produce the most efficacious therapeutic responses and the reproducibility of the outcomes. It is tempting to speculate that, with integration of this care in a setting of full medical and laboratory support, a better outcome may indeed be achieved in the future.

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